bluuebunny/crossref_metadata_2025 huggingface dataset:
428 The role of virtual visits in COVID-19 cardiovascular patients
Authors: Di Iorio Martina , Mei Mariachiara , Bernardini Alessia , Magnocavallo Michele , Vetta Giampaolo , Piro Agostino , Mariani Marco Valerio , Giunta Giuseppe , Quaglione Raffaele , Chimenti Cristina , Trivigno Sara , Mancone Massimo , Fedele Francesco , Lavalle Carlo
Published: December 2021

Aims

The outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic forced a reorganization of the healthcare system. In order to prevent potential risk of exposure, virtual visit (VV) has been implemented in the treatment and follow-up of COVID-19 patients with cardiovascular diseases. The aim of this study is to evaluate the feasibility and efficacy of VV in the management of post COVID-19 cardiovascular patients.

Methods and results

We enrolled all patients with cardiovascular comorbidities tested negative for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) and discharged from our Cardiology Department from January 2021 to June 2021. We scheduled a VV after 30 days from discharge to check the clinical status of the patients, optimize therapy, and establish a Follow-up protocol. Blood pressure, arterial oxygen saturation, heart rate and body weight were registered. To evaluate the patients’ satisfaction of VV, a questionnaire was administered. We performed 25 VVs in the study period; the mean age of patients was 67.5 ± 15.6 and male were 15 (65.2%). The mean duration of VV was 25.9 ± 4.6 min. The caregiver had an active role in nine (36%) cases. No urgent/emergent in-person examinations were performed. A high degree of patient satisfaction was reached and VV was preferred to in-person evaluation.

Conclusions

VV visit was useful to Follow-up post COVID-19 cardiovascular patients. A high degree of patient satisfaction was reached without jeopardizing quality of care.
782 Cardiopulmonary exercise testing in patients with COVID-19 at 3 months from hospital discharge
Authors: Fumagalli Carlo , Silverii Maria Vittoria , Zocchi Chiara , Tassetti Luigi , Lavorini Federico , Marcucci Rossella , Rasero Laura , Burgisser Costanza , Fattirolli Francesco , Marchionni Niccolò
Published: December 2021

Aims

The long-term COVID-19 effects are currently unknown. Whether and for how long symptoms extend beyond the acute phase of the disease is unresolved. Aim of this study was to determine the functional capacity of COVID-19 survivors by cardiopulmonary exercise testing (CPET) and describe its association with dyspnoea, the most frequent symptom after discharge from a tertiary care hospital.

Methods and results

All COVID-19 patients discharged from our tertiary care institution were enrolled in a prospective follow-up study which would assess clinical, instrumental and laboratory characteristics of COVID-19 survivors at 3 months from hospital discharge (i.e. long-covid). To limit bias in dyspnoea quantification, patients hospitalized in residential care facilities with severe cognitive impairment/disability, ischaemic cardiopathy, and/or heart failure and severe respiratory disease (i.e. chronic obstructive pulmonary disease) were excluded. Clinical evaluation included: peripheral blood samples including inflammatory cytokines, pulmonary function testing (functional respiratory and 6 min-walking test), lung ultrasound, ECG recording, and a comprehensive echocardiographic exam. All patients with peripheral oxygen desaturation at 6 min-walking test (SpO2 < 92%), dyspnoea and with a history of hospitalization in critical care settings were referred for CPET. Dyspnoea was classified with the Medical Research Council (MRC) scale. From June 2020 to May 2021, 198 patients were enrolled; overall, 42% of patients presented with dyspnoea at 3 months from hospital discharge with no difference according to disease severity on hospital admission (P = 0.233). Clinical, laboratory, and echocardiographic parameters were similar between patients with and without dyspnoea. At CPET, 61% of patients complaining dyspnoea showed a %peak VO2 lower than 85% of the predicted value, associated with a lower exercising tolerance and duration and with a globally reduced equivalent metabolic load (METS: 5.3 ± 1.2 vs. 6.6 ± 1.6, P = 0.003). Mean anaerobic threshold was lower for symptomatic patients (46 + 13 vs. 50 + 10, P = 0.03). At multivariable logistic regression analysis, after adjustment for age, number of comorbidities, and body mass index, only %peak VO2 (HR: 0.973; 95% CI: 0.948–0.998) and male gender (HR: 0.548; 95% CI: 0.328–0.999) were associated with dyspnoea.

Conclusions

At 3-months, almost 1-in-2 patients discharged for COVID-19 pneumonia presented with dyspnoea, irrespective of disease severity. Among patients undergoing CPET, only %peak VO2 and gender were associated with symptoms suggesting a potential systemic inflammatory-mediated response and important gender related differences for the long-covid.
404 Acute coronary syndromes after healing from COVID-19: report of the initial observation
Authors: Golino Michele , Licciardello Claudio , Matteo Federica , Giovenzana Fulvio Lorenzo Francesco , Franzosi Cinzia , Blasi Federico , Genoni Paola , Seganfreddo Francesca , Cadonati Cristina , Morello Matteo , Chierchia Valentina , Facciolo Caterina , Limido Alberto , Marazzato Jacopo , Angeli Fabio , De Ponti Roberto
Published: December 2021

Aims

Severe pulmonary complications are well described in the coronavirus disease 2019 (COVID-19) and cardiovascular diseases (CVDs) have been documented as well. Most patients (pts) recover quickly; nevertheless, the potential long-term cardiovascular sequalae of COVID-19 remain currently unknown. The aim was to report cases of acute coronary syndromes (ACS) after healing from COVID-19 and their features at coronary angiography; secondary purpose was to hypothesize the underlying mechanisms.

Methods and results

A retrospective study was performed by acquiring data from the electronic medical record. From January to June 2021, four hypertensive pts (64 ± 17 years old; three males) with no history of CVDs and previous symptomatic SARS-CoV-2 infection (mean interval from first positive molecular swab 47 ± 32 days; all recovered after 15 days with double negative swab) were admitted to the emergency department for ST-elevation myocardial infarction (3 anterior and one inferior). At admission, the SARS-CoV-2 molecular swab tested negative, left ventricle ejection fraction was 42 ± 12%, troponin T and Nt-proBNP values were 47 ± 24 ng/l and 1180 ± 978 ng/l, respectively. Emergency coronary angiography showed single-vessel acute thrombotic occlusion (in three cases of the anterior descending artery and in one case of the right coronary artery), with no evidence of atherosclerotic disease. Because of the high thrombotic burden, in all cases a mechanical thrombus aspiration system was used, tirofiban infusion started and no balloon angioplasty or drug-eluting stent implantation was necessary (Figures A–D). After 72 h, a second SARS-CoV-2 molecular swab tested also negative. In the following days, the pts gradually recovered and they were discharged home.

Conclusions

These cases deserve specific considerations both on the pathophysiologic mechanisms of the ACS possibly related to SARS-CoV-2 and on the subsequent long-term sequelae. Among various pathophysiologic mechanisms proposed, the high affinity of the spike protein for the angiotensin converting enzyme two receptor (expressed by both cardiac and endothelial cells) could explain direct cardiac viral infection and vasculitis with possible development of thrombosis. The latter could contribute both to acute and long-term cardiac sequelae, even months after the acute infection, configuring a sort of ‘cardiac post-Covid syndrome’. Whether and how long this status persists, making COVID-19 a risk factor for subsequent CVDs, is still an unresolved question. In this regard, continuous monitoring of these pts and larger future studies will be essential.
264 Cardiac and pulmonary sequelae after COVID-19 pneumonia: a case series
Authors: Marazzato Jacopo , Angeli Fabio , Verdecchia Paolo , Masnaghetti Sergio , Visca Dina , Mancinelli Antonella , Golino Michele , De Ponti Roberto
Published: December 2021

Aims

Although the new coronavirus (SARS-CoV-2) may cause an acute multiorgan syndrome (COVID-19), data are emerging on mid- and long-term sequelae of COVID-19 pneumonia. Since no study has hitherto investigated the role of both cardiac and pulmonary ultrasound techniques in detecting such sequelae, this study aimed at evaluating these simple diagnostic tools to appraise the cardiopulmonary involvement occurring after COVID-19 pneumonia.

Methods and results

Twenty-nine patients fully recovered from COVID-19 pneumonia were considered at our centre. On admission, all patients underwent 12-lead electrocardiogram (ECG) and transthoracic echocardiography (TTE) evaluation. Compression ultrasound (CUS) and lung ultrasound (LUS) were also performed. Finally, in each patient, pathological findings detected on LUS were correlated with the pulmonary involvement occurring after COVID-19 pneumonia as assessed on thoracic computed tomography (CT). Out of 29 patients (mean age 70 ± 10 years old; M 69%), prior cardiovascular and pulmonary comorbidities were recorded in 22 (76%). Twenty-seven patients (93%) were in sinus rhythm and two (7%) in atrial fibrillation. ECG repolarization abnormalities were extremely common (93%) and reflected the high prevalence of pericardial involvement on TTE (86%). Likewise, pleural abnormalities were frequently observed (66%). TTE signs of left and right ventricular dysfunction were reported in two patients only, but values of systolic pulmonary artery pressure were abnormal in 16 (55%) despite absence of prior comorbidities in 44% of them. Regarding LUS evaluation, most patients displayed abnormal values of diaphragmatic thickness and excursion (93%) which well correlated with the high prevalence (76%) of on pathological findings on CT scan. CUS ruled out deep vein thrombosis in all patients.

Conclusions

Data on cardiopulmonary sequelae after COVID-19 pneumonia are scarce. In our study, simple diagnostic tools (TTE and LUS) proved clinically useful for detection of cardiopulmonary involvement after COVID-19 pneumonia.
58 Effects of sodium–glucose co-transporter 2 (SGLT2) inhibitors on major cardiovascular events in Type 2 diabetic patients: a meta-analysis of randomized controlled trials
Authors: Bardi Luca , Paolillo Stefania , Bruzzese Dario , Esposito Cristina , Ambrosio Antonio , Prastaro Maria , Chirico Alfonsina , Colella Angela , Perrone-Filardi Pasquale , Gargiulo Paola
Published: December 2021

Aims

Sodium–glucose co-transporter-2 inhibitors (SGLT2i) reduce cardiovascular (CV) events in diabetic patients, with a consistent effect on heart failure (HF) related outcomes. However, the effects on ischaemic CV events appear less certain, in particular in patients with history of HF. The aim of this meta-analysis is to investigate CV benefit of SGLT2i and to assess the effects in patients with and without established atherosclerotic cardiovascular disease (ASCVD), with and without HF, and with estimated glomerular filtration rate < or ≥ 60 mL/min.

Methods

We searched PubMed, Embase, Cochrane, ISI Web of Science, SCOPUS, and clinicaltrial.gov databases. We performed a systematic review and meta-analysis of randomized, placebo-controlled, cardiovascular outcome trials (CVOT) of SGLT2i in diabetic patients, assessing the effects of SGLT2i on 3-point MACE [CV death, non-fatal myocardial infarction (MI), non-fatal stroke] and composite of HF hospitalization or CV death.

Results

Of 205 articles, 7 CVOTs were included in the meta-analysis. Compared to placebo, SGLT2i significantly reduced by 10% the risk of 3-point MACE (HR 0.90; P = 0.025) (Figure panel A) and the risk of CV death or HF hospitalization by 24% (HR 0.76; P < 0.001) (Figure panel B). SGLT2i significantly reduced HF hospitalization by 30% (HR 0.70; P < 0.001), with consistent effects in all subgroups analysed, CV death by 17% (HR 0.83; P = 0.035) and all-cause mortality by 18% (HR 0.82; P = 0.024). No significant effects were observed on MI and stroke.

Conclusions

SGLT2i significantly reduce CV outcome in diabetic patients. SGLT2i remarkably and consistently reduce HF hospitalization, in patients with and without HF at baseline and independently on the presence of ASCVD.
239 Role of eNOS genetic variants on ischaemic heart disease susceptibility and acute coronary syndrome presentation
Authors: D'Amato Andrea , Severino Paolo , Prosperi Silvia , Magnocavallo Michele , Mariani Marco Valerio , Netti Lucrezia , Birtolo Lucia Ilaria , De Orchi Paolo , Chimenti Cristina , Maestrini Viviana , Miraldi Fabio , Lavalle Carlo , Caputo Viviana , Palmirotta Raffaele , Mancone Massimo , Fedele Francesco
Published: December 2021

Aims

IHD is determined by inadequate coronary blood supply to myocardium and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Results validation on larger cohorts and new population is needed. The aim of the study is to evaluate the association among the allelic variants of eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility, and its clinical presentation.

Methods

A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD); G2, coronary microvascular dysfunction (CMD); G3, control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG, and TT of rs1799983 for NOS3 gene, encoding for eNOS has been performed.

Results

rs1799983_GT is significantly more expressed by ischaemic groups (G1 and G2) compared with G3. The TT variant is significantly more expressed by G1 group, compared with G2 group. Among ischaemic patients, GT is significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentation. At multivariate analysis, the allelic variant GT may represent an independent predictor of IHD and ACS presentation.

Conclusions

The SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently from cardiovascular risk factors. These results may be useful for the prediction of IHD development, in particular with acute clinical manifestation. It may allow the early identification of patients at high risk to develop IHD with an ACS, promoting a genetic-based prevention strategy against IHD.
419 High-sensitivity troponins for outcome prediction in the general population: a systematic review and meta-analysis
Authors: Aimo Alberto , Georgiopoulos Georgios , Panichella Giorgia , Vergaro Giuseppe , Passino Claudio , Emdin Michele , Clerico Aldo
Published: December 2021

Aims

High-sensitivity (hs) assays allow to measure cardiac troponin T and I (cTnT/I) even in healthy individuals. The higher hs-cTn values, the higher the ongoing cardiomyocyte damage, and then reasonably the risk of developing symptomatic cardiac disease.

Methods and results

We retrieved all studies evaluating the prognostic value of hs-cTnT or I in the general population. We calculated pooled hazard ratio (HR) values for all-cause and cardiovascular death, cardiovascular events and heart failure (HF) hospitalization. We included 24 studies for a total of 203 202 subjects; 11 studies assessed hs-cTnT and 14 hs-cTnI. One standard deviation (SD) increase in baseline hs-cTn was associated with a 23% higher risk of all-cause death (HR: 1.226, 95% CI: 1.083–1.388, P < 0.001, I2 = 88.5%); all these studies dosed hs-cTnI. In an exploratory analysis on three studies with 25 760 subjects, hs-cTn predicted cardiovascular death (HR: 1.822, 95% CI: 1.241–2.674, P = 0.002, I2 = 87.2%). After synthesizing nine studies with 58 565 subjects, hs-cTn predicted cardiovascular events (HR: 1.328, 95% CI: 1.167–1.513, P < 0.001, I2 = 93.8%). Both hs-cTnT (HR: 1.627, 95% CI: 1.145–2.311, P < 0.001) and hs-cTnI (HR: 1.260, 95% CI: 1.115–1.423, P < 0.001; p for interaction <0.001). Furthermore, in 10 studies with 61 467 subjects, hs-cTn predicted HF hospitalization (HR: 1.493, 95% CI: 1.368–1.630, P < 0.001, I2 = 76.6%). Both hs-cTnT (HR: 1.566, 95% CI: 1.303–1.883, P < 0.001) and hs-cTnI (HR: 1.467, 95% CI: 1.321–1.628, P < 0.001) were associated with HF ho (p for interaction <0.001).

Conclusions

hs-cTn values hold strong prognostic value in subjects from the general population, predicting the risk of all-cause and cardiovascular mortality, cardiovascular events, and HF hospitalization.
298 Domiciliary periodic Levosimendan infusions in advanced heart failure: a single centre experience
Authors: Blasi Federico , Seganfreddo Francesca , Croce Francesca , Morello Matteo , Oliva Carlo Agostino , Refugjati Taulant , Golino Michele , Cadonati Cristina , Ceriani Francesca , Marazzato Jacopo , Vecchi Andrea Lorenzo , Ponti Roberto De
Published: December 2021

Aims

There are several studies that describes a possible use of periodical infusions of Levosimendan in patients with advance heart failure (AHF). In these studies, Levosimendan was administered in ambulatory settings (LevoRep, LION-HEART) or during 24 h of hospital stay (LAICA) and for a maximum of 12 months. Currently there is no strong evidence about the feasibility and safety of performing the infusions in an out of hospital setting. Aim of our study was to analyse the feasibility and safety of periodical Levosimendan infusions in AHF patients, in an out of hospital setting for palliative use.

Methods and results

Aretrospective study was conducted from June 2016 to September 2021 on AHF patients, followed by our centre for periodic infusion of Levosimendan. All patients were previously implanted with an ICD, were ineligible for heart transplant or for ventricular assist devices. All patients on each cycle underwent a cardiological evaluation, a blood sample (complete blood count, biochemical profile, coagulation profile, and NTproBNP), and Levosimendan was administrated with a wearable infusion pump (CADD-Legacy®; Smiths Medical). The patient went home and came back the day after, to return the pump and for reassessment. We collected data on the different infusion regimen, adapted for every patient, and on adverse events during infusions.

We enrolled 11 patients with AHF, 9 (82%) of which of ischaemic origin, 2 (18%) were female, median age 72 years (IQR: 64–75), 10 with NYHA class III, 1 with a NYHA class IV, for a total of 231 infusions, with a median Follow-up of 459 days (IQR 132; 783). A total dose of 6.25 mg was administered at 0.05 μg/kg/min in 24 h. In five patients the infusion was of 12.5 mg at 0.1 μg/kg/min rate in 24 h and in other three patients at 0.05 μg/kg/min in 48 h. The median interval between administrations was 21 days (IQR: 14–24.5). Mild adverse events (i.e. that did not contraindicate successive cycles) were 7 on 231 infusions (3.0%): symptomatic hypotension (four cases, 1.7%), loss of consciousness (two cases 0.9%), bleeding for vein access misplacement (one case, 0.4%). No serious adverse event such as sustained or malignant arrhythmia, allergic reaction, or need for hospital admission were recorded.

Conclusions

The administration of Levosimendan at home with a wearable iv pump is safe and well tolerated. This practice allows to reduce infusion costs of day hospital regime and to lengthen the time available for drug infusion, thus reducing the events caused by a too rapid infusion.
633 Efficacy of additional medical therapies in patients with heart failure, reduced ejection fraction, and chronic kidney disease already receiving neurohormonal inhibitors: a network meta-analysis
Authors: Marzo Vincenzo De , Tricarico Lucia , Zoccai Giuseppe Biondi , Correale Michele , Brunetti Natale Daniele , Canepa Marco , Ferrari Gaetano Maria De , Castagno Davide , Porto Italo , Ameri Pietro
Published: December 2021

Aims

We assessed the efficacy of add-on drugs in patients with heart failure with reduced ejection fraction (HFrEF) and concomitant chronic kidney disease (CKD) already receiving neurohormonal inhibition (NEUi).

Methods and results

The literature was systematically searched for phase 3 randomized controlled trials (RCTs) involving ≥90% patients with left ventricular ejection fraction <45%, of whom <30% were acutely decompensated, and with published information about the subgroup of estimated glomerular filtration rate <60 ml/min/1.73 m2. Six RCTs were included in a study-level network meta-analysis evaluating the effect of NEUi, ivabradine, angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv mecarbil (OM) on a composite outcome of cardiovascular death or hospitalization for heart failure. In a fixed-effects model, SGLT2i (HR: 0.78, 95% CrI: 0.69–0.89), ARNI (HR: 0.79, 95% CrI: 0.69–0.90), and ivabradine (HR: 0.82, 95% CrI: 0.69–0.98) decreased the risk of the composite outcome vs. NEUi, whereas OM did not (HR: 0.98, 95% CrI: 0.89–1.10). A trend for improved outcome was also found for vericiguat (HR: 0.90, 95% CrI: 0.80–1.00). In indirect comparisons, both SLGT2i (HR: 0.80, 95% CrI: 0.68–0.94) and ARNI (HR: 0.80, 95% CrI: 0.68–0.95) reduced the risk vs. OM; furthermore, there was a trend for a greater benefit of SGLT2i vs. vericiguat (HR: 0.88, 95% CrI: 0.73–1.00) and ivabradine vs. OM (HR: 0.84, 95% CrI: 0.68–1.00). Results were comparable in a random-effects model and in sensitivity analyses. SUCRA scores were 81.8%, 80.8%, 68.9%, 44.2%, 16.6%, and 7.8% for SGLT2i, ARNI, ivabradine, vericiguat, OM, and NEUi, respectively.

Conclusions

Expanding pharmacotherapy beyond NEUi improves outcomes in HFrEF with CKD.

633 Figure
257 Sodium-glucose CO-transporter-2 inhibitors eligibility in patients with heart failure with reduced ejection fraction
Authors: Ferrari Ilaria , Cicogna Francesco , Tota Claudia , Calò Leonardo , Monzo Luca
Published: December 2021

Aims

The sodium–glucose co-transporter-2 (SGLT2) inhibitors dapagliflozin and empagliflozin have been demonstrated to reduce adverse cardiovascular outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Limited data are available characterizing the generalizability of SGLT2 inhibitors treatment in the clinical practice. The aim of the study was to evaluate the proportion of outpatients with HFrEF that would be eligible for SGLT2 inhibitors in a contemporary real-world population.

Methods and results

We retrospectively evaluated patients with chronic stable HFrEF followed-up at the HF outpatient clinic of our institution. Patients’ eligibility was assessed according to the entry criteria of DAPA-HF (dapagliflozin) and EMPEROR-Reduced (empagliflozin) trials and to US Food and Drug Administration (FDA) label criteria (only dapagliflozin). A total of 441 HFrEF patients was enrolled. According to the major inclusion and exclusion criteria from DAPA-HF and EMPEROR-Reduced trials, 198 (45%) patients would be candidates for initiation of both dapagliflozin and empagliflozin, 61 (14%) would be eligible only to dapagliflozin and 23 (5%) only to empagliflozin, without significant differences between diabetic and non-diabetic patients (P = 0.23). Among patients not suitable for gliflozins treatment (159 patients; 36%), the major determinant of ineligibility was the failure to achieve the predefined NT-proBNP inclusion threshold. Excluding NTproBNP as per FDA label criteria, dapagliflozin eligibility increased to 86%.

Conclusions

In our real-world analysis a large proportion of HFrEF patients would be candidates for initiation of SGLT2 inhibitors, supporting its broad generalizability in clinical practice. This would be expected to reduce morbidity and mortality in eligible patients.
348 Uric acid is associated with acute heart failure and cardiogenic shock at presentation in acute coronary syndrome patients
Authors: Maloberti Alessandro , Rebora Paola , Centola Marco , Morici Nuccia , Sacco Alice , Scarpellini Sara , Occhino Giuseppe , Viola Giovanna , Oreglia Jacopo , Castini Diego , Carugo Stefano , Algeri Michela , Valsecchi Maria Grazia , Oliva Fabrizio , Giannattasio Cristina
Published: December 2021

Aims

we focused on the role of Uric Acid (UA) as a possible determinant of Heart Failure (HF) related issues in Acute Coronary Syndromes (ACS) patients. Main outcome were acute HF and cardiogenic shock at admission, secondary outcomes were the need of Non Invasive Ventilation (NIV) use and the admission Left Ventricular Ejection Fraction (LVEF).

Methods and results

we consecutively enrolled 1269 ACS patients admitted to the cardiological Intensive Care Unit of the Niguarda and San Paolo hospitals (Milan, Italy) from June 2016 to June 2019. Hyperuricaemia was defined as a value higher than 6 mg/dl for females and 7 mg/dl for males.

All the evaluated outcomes occurred more frequently in the hyperuricemic subjects (n = 292): acute HF 35.8 vs. 11.1% (P < 0.0001), cardiogenic shock 10 vs. 3.1% (P < 0.0001), NIV 24.1 vs. 5.1% (P < 0.0001) with lower admission LVEF (42.9 ± 12.8 vs. 49.6 ± 9.9, P < 0.0001). By multivariable analyses, UA was confirmed to be significantly associated with all the outcomes with the following odds ratio (OR): acute HF OR = 1.119; 95% CI: 1.019–1.229; cardiogenic shock OR = 1.157; 95% CI: 1.001–1.337; NIV use OR = 1.208; 95% CI: 1.078–1.354; LVEF β = −0.999; 95% CI: −1.413 to − 0.586.

Conclusions

The main result of our study was the finding of a significant association between UA and acute HF, cardiogenic shock, NIV use and LVEF. Due to the cross-sectional nature of our study no definite answer on the direction of these relationship can be drawn and further longitudinal study on UA changes over time during an ACS hospitalization are needed.
128 Clinical impact of changes in mitral regurgitation severity after optimization of medical therapy in heart failure: insights from BIOSTAT-CHF
Authors: Pagnesi Matteo , Adamo Marianna , Sama Iziah E. , Anker Stefan D. , Cleland John G. , Dickstein Kenneth , Filippatos Gerasimos S. , Inciardi Riccardo M. , Lang Chim C. , Lombardi Carlo M. , Ng Leong L. , Ponikowski Piotr , Samani Nilesh J. , Zannad Faiez , Van Veldhuisen Dirk J. , Voors Adriaan A. , Metra Marco
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.
581 Ventricular–arterial coupling derived from proximal aortic stiffness and aerobic capacity across the heart failure spectrum
Authors: Pugliese Nicola Riccardo , Balletti Alessio , Armenia Silvia , Biase Nicolò De , Faita Francesco , Ruschitzka Frank , Ghiadoni Lorenzo , Taddei Stefano , Williams Bryan , Antonini-canterin Francesco , Masi Stefano
Published: December 2021

Aims

Ventricular–arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulse wave velocity, PWV) and myocardial deformation (global longitudinal strain, GLS). To evaluate VAC across the spectrum of heart failure (HF).

Methods and results

We introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). We measured PWVs and GLS in 155 healthy controls, 75 subjects at risk of developing HF (American College of Cardiology/American Heart Association Stage A-B) and 236 patients in HF Stage C with preserved (HFpEF, n = 104) or reduced ejection fraction (HFrEF, n = 132). We evaluated peak oxygen consumption (VO2) and peripheral extraction (AVO2diff) using combined cardiopulmonary-echocardiography exercise stress. aa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (P < 0.01). PWVs were directly related and increased with age (all P < 0.0001). cf-PWV/GLS was similarly compromised in HFrEF (1.08 ± 0.36) and HFpEF (1.05 ± 0.22), while aa-PWV/GLS was more impaired in HFpEF (0.69 ± 0.11) than HFrEF (0.60 ± 0.15; P < 0.01). Stages A and B had values of cf-PWV/GLS and aa-PWV/GLS (0.66 ± 0.25 and 0.47 ± 0.12) higher than controls (0.47 ± 0.10 and 0.40 ± 0.10) but lower than Stage C (all P < 0.01). Peak AVO2diff was inversely related with cf-PWV/GLS and aa-PWV/GLS (all P < 0.01). cf-PWV/GLS and aa-PWV/GLS independently predicted peak VO2 in the overall population (adjusted R2 = 0.32 and 0.35; all P < 0.0001) but only aa-PWV/GLS was independently associated with flow reserve during exercise (R2 = 0.51; P < 0.0001).

Conclusions

Abnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/GLS.
192 Study of endothelial function and vascular stiffness in patients affected by dilated cardiomyopathy on treatment with sacubitril/valsartan
Authors: Amore Ludovica , Alghisi Fabio , Cersosimo Angelica , Cimino Giuliana , Pascariello Greta , Pancaldi Edoardo , Bernardi Nicola , Calvi Emiliano , Lombardi Carlo , Vizzardi Enrico , Metra Marco
Published: December 2021

Aims

It has already been demonstrated the efficacy of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction, but many of its properties are still unknown especially regarding its effects on endothelial dysfunction and arterial stiffness.

Methods and results

To this purpose, a longitudinal study involving 15 patients with dilated cardiomyopathy with reduced left ventricular ejection fraction (LVEF) was started; the purpose was collecting at the beginning and at the end of the study blood pressure measurements, transthoracic echocardiography images, parameters of endothelial function with peripheral arterial tonometry (EndoPAT®), and non-invasive evaluation of the aortic stiffness parameters by using applanation tonometry (SphygmoCor® Px system). Aortic stiffness parameters weren’t different at 6 months, compared to baseline. There was a slight, not significant increase in augmentation pressure (P = 0.889), augmentation index (P = 0.906), and sphygmic wave velocity (P = 0.263). Systolic, diastolic, and differential central arterial pressure didn’t change. RHI (reactive hyperaemia index) increased significantly after 6 months (P = 0.001) as well as augmentation index corrected for 75 b.p.m. Ejection fraction (32.21% ± 5.7 to 38.43% ± 8.4; P = 0.010) and diastolic dysfunction degree (P = 0.021) improved significantly. Mitral regurgitation improvement wasn’t statistically significant (P = 0.116). Tricuspid annular plane systolic excursion didn’t change while pulmonary systolic arterial pressure increased, although not significantly (22.83 mmHg ± 4 to 27.33 mmHg ± 6; P = 0.068) and within the normal range values.

Conclusions

Sacubitril/valsartan can improve endothelial function significantly in patients with dilated cardiomyopathy and reduced LVEF. It can also improve left ventricular function, mitral regurgitation, and diastolic function. Conversely, this drug seems to have no effects on vascular stiffness.
259 Incidence, predictors, and prognostic role of complications occurring during intracoronary provocative test with acetylcholine in patients with myocardial ischaemia and non-obstructive coronary arteries
Authors: Montone Rocco Antonio , Rinaldi Riccardo , Gurgoglione Filippo , Del Buono Marco , Russo Michele , Caffè Andrea , Vecchia Giulia La , Niccoli Giampaolo , Crea Filippo
Published: December 2021

Aims

Coronary provocative test with acetylcholine (ACh) is of utmost importance and increasingly used in patients with myocardial ischaemia and non-obstructive coronary arteries. However, data on safety, predictors, and prognostic role of complications during intracoronary provocative testing are scarce. We aimed at assessing the safety of ACh provocative test in patients with myocardial ischaemia and non-obstructive coronary arteries. Moreover, we evaluated the predictors and the prognostic implications of complications occurring during the provocative test.

Methods and results

We prospectively enrolled consecutive patients undergoing intracoronary ACh provocative test for suspected myocardial ischaemia with angiographic evidence of non-obstructive coronary arteries. Complications during the ACh test were collected. Occurrence of major adverse cardiac events (MACE), arrhythmic events at 24-h ECG dynamic Holter monitoring and angina status were assessed at follow-up. We enrolled 310 patients [mean age 60.6 ± 11.9; 169 (54.5%) chronic coronary syndromes (CCS) and 141 (45.5%) with myocardial infarction and non-obstructive coronary arteries (MINOCA)]. The overall incidence of complications was low (9%) with a similar incidence in MINOCA and CCS [10 (7.1%) vs. 18 (10.7%), P = 0.276, respectively]. At multivariate logistic regression analysis, a previous history of paroxysmal atrial fibrillation [odds ratio (OR): 12.324, confidence interval (CI): 95% (4.641–32.722), P = 0.015] and moderate/severe diastolic dysfunction [OR: 3.827, 95% CI (1.296–11.304), P = 0.015] were independent predictors for occurrence of complications. The occurrence of complications was not associated with a worse clinical outcome at follow-up (median follow-up 22 months) in terms of both MACE, arrhythmic events and angina burden.

Conclusions

Intracoronary provocative testing with ACh test is safe in patients with myocardial ischaemia and non-obstructive coronary arteries (including MINOCA patients). History of paroxysmal atrial fibrillation and moderate/severe diastolic dysfunction predicted the occurrence of complications during ACh test. However, occurrence of complications did not portend a worse prognosis at follow-up in terms of MACE, arrhythmic events, and angina burden.
719 Prevalence and clinical impact of high platelet reactivity in patients with chronic kidney disease treated with percutaneous coronary intervention: an updated systematic review and meta-analysis
Authors: Mangiacapra Fabio , Paolucci Luca , Viscusi Michele Mattia , Mangiacapra Roberto , Ferraro Pietro Manuel , Nusca Annunziata , Melfi Rosetta , De Luca Leonardo , Gabrielli Domenico , Ussia Gian Paolo , Grigioni Francesco
Published: December 2021

Aims

High platelet reactivity (HPR) on clopidogrel and chronic kidney disease (CKD) are recognized as potent risk factors for adverse outcomes in patients suffering coronary artery disease (CAD) and undergoing percutaneous coronary intervention (PCI). However, conclusive evidence regarding their reciprocal interaction and the consequent impact on clinical events is still lacking. We performed a meta-analysis with the aim to evaluate the prevalence of HPR in patients with and without CKD and the incidence of major adverse cardiovascular events (MACE) according to the renal and platelet function status in current literature (co-primary endpoints). Secondary endpoints were myocardial infarction (MI), all cause death and definite/probable stent thrombosis (ST).

Methods and results

We searched on PubMed, EMBASE, and Cochrane Library studies investigating CKD and HPR on clopidogrel in patients suffering CAD who underwent PCI and their related outcomes. Overall, 13 studies including 22.464 patients were selected. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model with the Mantel–Haenszel method. Patients with CKD presented significantly higher odds of HPR compared with those without CKD [OR: 1.51 (95% CI: 1.29–1.76)]. In patients without CKD, HPR was associated with increased odds of MACE [OR: 1.31 (95% CI: 1.01–1.72)], MI [OR: 1.48 (95% CI: 1.17–1.86)] and definite/probable ST [OR: 2.45 (95% CI: 1.08–5.60)]. In patients with CKD, HPR was associated with higher odds of both MACE [OR: 1.61 (95% CI: 1.14–2.27)] and MI [OR: 1.69 (95% CI: 1.11–2.59)], compared to those without HPR.

Conclusions

Our analysis shows that HPR on clopidogrel is more frequent in patients with CKD treated with PCI. Patients with HPR are exposed to a high risk of MACE after PCI, regardless of the renal function status.
184 The presence of atrial fibrillation in acute myocardial infarction patients and hyperglycaemia
Authors: Fabrizio Michele , Paolisso Pasquale , Bergamaschi Luca , Angeli Francesco , Toniolo Sebastiano , Magnani Ilenia , Donati Francesco , Stefanizzi Andrea , Sansonetti Angelo , Armillotta Matteo , Chiti Chiara , Bartoli Lorenzo , Rinaldi Andrea , Foà Alberto , Casella Gianni , Galiè Nazzareno , Pizzi Carmine
Published: December 2021

Aims

In patients with acute myocardial infarction (AMI), hyperglycaemia is a common feature determining a worse prognosis. Few studies have examined the relationship between hyperglycemic status and atrial fibrillation in-hospital stay. To evaluate the relationship between admission hyperglycaemia (aHGL) and occurrence of atrial fibrillation (AF) in-hospital stay in patients with AMI, categorized as myocardial infarction with obstructive coronary artery disease (MIOCA) and myocardial infarction with nonobstructive coronary artery disease (MINOCA).

Methods and results

Hyperglycaemia was defined as a serum glucose level ≥140 mg/dl at the time of hospital admission. AF was defined as a beat-to-beat variability in cycle length and morphology with irregular fibrillatory waves on surface ECG. Among 2702 patients (32.1% were female, mean age was 70.1 ± 13.4 years), 24.2% were diabetic. Out of 2702 patients, 2457 were MIOCA and 245 (9.1%) were MINOCA patients. At admission, the mean value of serum glucose levels was 146 ± 66 mg/dl. At hospital admission, hyperglycemic status was present in 37.7% of patients and 8.3% presented atrial fibrillation. At hospital admission, atrial fibrillation (aAF) was significantly frequent in hyperglycemic than normoglycaemic patients (11.5% vs. 6.3%, respectively; P < 0.001). In aHGL MIOCA patients had a higher rate of aAF (10.7%) than normoglycaemic MIOCA (6.4%; P < 0.001). In aHGL MINOCA patients had 31% aAF than normoglycaemic MINOCA patients (7.5%; P < 0.001). During the hospital stay, the new onset of atrial fibrillation was higher in aHGL than normoglycaemic status in total population (6.3% vs. 2.9%, P < 0.001), in MIOCA subgroup (6.3% vs. 3.1%, P < 0.001) and MINOCA subgroup (7.3% vs. 1.5%, P = 0.003). Multivariate analysis adjusted for age, sex, and diabetes revealed that the presence of hyperglycaemia was an independent predictor for the onset of atrial fibrillation (OR: 1.7; 95% CI: 1.1–2.6; P = 0.02).

Conclusions

Hyperglycaemia was an independent predictor of new atrial fibrillation during hospitalization in patients with AMI. Moreover, at hospital admission, patients with hyperglycemic status presented a higher incidence of atrial fibrillation, both in MIOCA and MINOCA subgroups. Further studies are needed to understand the biological mechanisms involved in these associations.
729 Clinical profile and management of acute myocardial infarction in elderly patients
Authors: Romano Letizia Rosa , De Rosa Salvatore , Kosuke Fujita , Sabatino Jolanda , Polimeni Alberto , Sorrentino Sabato , Spaccarotella Carmen , Mongiardo Annalisa , Indolfi Ciro , Canino Giovanni
Published: December 2021

Aims

The management of acute myocardial infarction (AMI) in elderly patients is often challenging for their peculiar clinical profile and the limited clinical evidence available. This represents a major unmet need in cardiovascular medicine, given the progressive ageing of population in western Countries. To investigate the clinical characteristics of elderly patients with AMI at a single tertiary university hospital.

Methods and results

The EMIR is an ongoing registry including elderly patients (≥75 years) consecutively referred to a single tertiary centre with diagnosis of acute myocardial Infarction with indication for coronary angiography. A total of 760 patients were enrolled to date, 39.6% were female, while mean age was 80 ± 4 years. Most patients had a NSTEMI, while 28% had a STEMI. Time from symptoms’ onset to presentation was 9.4 ± 14.6 for STEMI and 26.5 ± 30.4. Percutaneous coronary intervention (PCI) was performed in 64% of cases. Concomitant PCI of a non-target lesion (NTL) was performed within the same procedure in 8.8% of cases. A staged PCI of NTL was performed in 14% of cases. An elective surgical revascularization was performed after PCI of the IRA in 2.1% of cases. Altogether, a complete revascularization was achieved in 43% of cases before discharge. No evidence of critical coronary stenoses (CCS) was reported in 12.1% of cases, more frequently in females (18%) than in males (8.3%). Patients with no CCS were younger (P = 0.007), more frequently female (P < 0.001), had lower LV-EF (P = 0.002) and a longer time from symptoms’ onset to presentation (P = 0.008). Atrial fibrillation (AF) was present in 17.4% of patients, although only 12.1% of patients had any knowledge of carrying AF. Among patients with AF, 16.7% had no CCS, while the remaining had a formal indication to a combined antiplatelet/anticoagulant treatment.

Conclusions

Elderly patients with AMI are a specific population, posing peculiar clinical needs and demanding dedicated clinical management protocols.
448 Comparison of quantitative flow ratio, Pd/Pa, and diastolic hyperaemia-free ratio vs. fractional flow reserve in non-culprit lesion of patients with non-ST-segment elevation myocardial infarction
Authors: Tebaldi Matteo , Biscaglia Simone , Erriquez Andrea , Penzo Carlo , Tumscitz Carlo , Scoccia Alessandra , Marrone Andrea , Scala Antonella , Gibiino Federico , Pompei Graziella , Tolomeo Paolo , Campo Gianluca
Published: December 2021

Aims

To investigate the correlation between quantitative flow ratio (QFR), Pd/Pa, diastolic hyperaemia-free ratio (DFR), and fractional flow reserve (FFR, gold standard) in non-culprit lesion (NCL) of patients with non ST-segment elevation myocardial infarction (NSTEMI). The non-hyperemic pressure ratio (NHPR) and the angiography-based indexes have been developed to overcome the limitation of the use of the FFR.

Methods and results

Between January and December 2019, 184 NCL from 116 NSTEMI patients underwent physiologic assessment and were included in the study. NCLs were investigated with QFR, Pd/Pa, DFR, and FFR. Mean values of QFR, Pd/Pa, DFR, and FFR were 0.85 ± 0.10, 0.92 ± 0.07, 0.93 ± 0.05, and 0.84 ± 0.07, respectively. DFR and FFR showed a good correlation (r = 0.76). Bland and Altman plot showed a mean difference of 0.080. DFR diagnostic accuracy was 88%. The area under the ROC curve (AUC) for DFR was 0.946 (95% CI: 0.90–0.97, P = 0.0001). Similar findings were reported for Pd/Pa [r = 0.73; mean difference 0.095, diagnostic accuracy 84%, AUC 0.909 (95% CI: 0.85–0.94, P = 0.0001)] and QFR [r = 0.68; mean difference: 0.01; diagnostic accuracy: 88%, AUC: 0.964 (95% CI: 0.91–0.98, P = 0.0001)]. FFR, QFR, Pd/Pa, and DFR identified 31%, 32%, 30%, and 32% potentially flow-limiting lesions, respectively.

Conclusions

In NSTEMI patients, QFR, Pd/Pa, and DFR showed equivalence as compared to gold standard FFR in the discrimination of non-culprit lesions requiring revascularization.
96 Meta-analysis of placebo-controlled trials of Levosimendan in acute myocardial infarction
Authors: Tumminello Gabriele , Cereda Alberto , Barbieri Lucia , Biondi-zoccai Giuseppe , Lucreziotti Stefano , Mafrici Antonio , Carugo Stefano
Published: December 2021

The treatment of acute myocardial infarction is the early revascularization strategy. Heart failure and cardiogenic shock may complicate acute myocardial infarction nevertheless the best disposable strategy applied. Levosimendan is relatively new drug to treat heart failure with a peculiar mechanism of action: calcium sensitization of myocardial fibres. Levosimendan has a direct inotropic effect but also pleiotropic effects; through the K+ATP channels opening it has also a vasodilator effect with may participate concretely to the global effects of the drug. Literature has focused the attention on the anti-heart failure and anti-cardiogenic shock properties of Levosimendan, but it may have effects also preventing the development of myocardial insufficiency in the acute setting of acute myocardial infarction. Scope of the meta-analysis is to evaluate the effect of Levosimendan on acute myocardial infarction in placebo-controlled trials.

Based on the eight studies selected we found a beneficial effect of Levosimendan on acute and long-term mortality of patients affected by acute myocardial infarction with no significative increase in adverse events (Figure 1). With caution in interpreting the results of this meta-analysis, our data support the idea that Levosimendan may already have a role in the treatment of acute ischaemic heart disease. Further studies, specifically designed to investigate the early role in the treatment of ischaemic heart failure, are needed.