bluuebunny/crossref_metadata_2025 huggingface dataset:
98 Takotsubo syndrome in COVID-19 era: is psycological distress the key?
Authors: Barbieri Lucia , Galli Federica , Conconi Barbara , Gregorini Teresa , Lucreziotti Stefano , Mafrici Antonio , Pravettoni Gabriella , Sommaruga Marinella , Carugo Stefano
Published: December 2021

Covid-19 pandemic, starting from Wuhan, China has spread all over the word and Italy was one of the most affected countries, especially in Lombardy, where, on 20 February the first case was confirmed. Italian Government ordered a national lockdown on the 9 March 2020, forcing the population to severe restrictive isolation measures. The burden on mental health of the medical emergency related to COVID-19 is progressively been revealed. Takotsubo syndrome (TTS), is estimated to represent 1–3% of patients admitted with suspected STEMI, mostly affecting elderly women with emotional stress and/or acute illness preceding the presentation. Comparing patients hospitalized from February to May 2020 with those of the corresponding period in 2019 we observed a significantly increased number of TTS diagnosis in 2020 (11 patients in 2020 vs. 3 in 2019), especially during the first period of lockdown. The only two males were patients with COVID-19 and were the only two who died in hospital. At psychological examination all patients enrolled report to have lived a particularly stressful experience at IES-R in the last year, without presenting the symptoms of a post-traumatic stress disorder. Most patients were positive to the allostatic overload. Only one patient showed a clinical cut-off for HADS and no one for the fear COVID-19 scale. We finally concluded that subjects with pre-pandemic psychological distress may have experienced additional psychological overload, opening the door to TTS by a series of physiological alterations as the secretion of cortisol and catecholamines, making the subject more vulnerable to the onset of TTS.
527 An incidental diagnosis in a patient with SARS-CoV-2 pneumonia
Authors: Bava Annita , Aricò Concetta Nadia , Caridi Rocco , Rodà Filippo , Franzutti Claudio , Scappatura Giuseppe , Grillone Nadine , Rao Massimo
Published: December 2021

Hypertrophic cardiomyopathy (HCM) is the most frequent genetic disease of the myocardium, with a prevalence of 1:500 cases in the general population. The salient feature is a hypertrophy, symmetrical or not, of the walls of the left ventricle (mainly the septum, but also less typical locations, such as the apex or the infero-lateral wall), not linked to abnormal load conditions. HCM is mostly an autosomal dominant inherited disease with incomplete penetrance and variable expressivity, mainly linked to mutations in genes coding for sarcomeric proteins. Several studies have shown an up-regulation of the ACE-2 gene, perhaps indicative of a compensatory anti-hypertrophic and anti-fibrotic response of the myocardium, in hypertrophic cardiomyopathy. Being the ACE-2 receptor target of the SARS-CoV-2 virus, these patients may have an increased risk of infection and a worse outcome.

A 47-year-old man, with no known comorbidities, was hospitalized in our Emergency Medicine Department for bilateral SARS-CoV-2 pneumonia. Noninvasive mechanical ventilation c-PAP (FiO2 60%, PEEP 7.5 cmH2O) was started for hypoxemic respiratory failure and an ECG showed diffuse ventricular repolarization abnormalities suggestive of left overload (asymmetric negative T waves V4–V6, in I, II, and aVL, flat in aVF. Figure 1), with a deep Q wave in III. The patient was asymptomatic for chest pain and equivalents and D-dimer and indices of myocardionecrosis were normal. Echocardiographic evaluation was performed, with evidence of marked asymmetric concentric hypertrophy of the left ventricle (interventricular septum: 16 mm), without significant anomalies in segmental kinetics, noteworthy valvulopathies, and pericardial effusion. The family and personal medical history were negative for syncope, sudden cardiac death, and resuscitated cardiac arrest and the estimated risk of sudden cardiac death at 5 years (HCM Risk-SCD) was <4% (1.33%). The diagnostic hypothesis of non-obstructive hypertrophic cardiomyopathy was advanced. During hospitalization, ECG monitoring showed no sustained ventricular arrhythmias and the patient remained asymptomatic for dyspnoea, chest pain, and equivalents. Subsequent echocardiograms showed no new changes. A progressive weaning from oxygen support was carried out and, after 30 days, the patient was discharged to home fiduciary isolation, with optimal cardiological therapy and indication to study with cardiac magnetic resonance to the negativization of the nasal swab for SARS-CoV-2. MRI, performed about 2 months later, confirmed the suspicion of hypertrophic cardiomyopathy, with no signs of late enhancement in T1-weighted sequences (Figure 2). The patient was then referred to a genetic study and cardiological follow-up, still in progress.
553 Myocarditis after COVID-19 vaccination—a case series
Authors: Bricoli Serena , Cacciola Giovanna , Barocelli Federico , Guerra Clelia , Zardini Marco
Published: December 2021

Myocarditis has been recognized as a rare complication of SARS-CoV-2 infection even in the absence of lung involvement and recent histological findings suggest that COVID-19-related myocardial damage may differ from other typical lymphocytic myocarditis associated with other viruses and could be possibly linked to diffuse infiltration of monocytes and macrophage leading to microvascular dysfunction and cell necrosis. SARS-CoV-2 vaccines have been well tolerated and associated with decreasing burden of disease in areas with high vaccination rates. Minor side-effects have been frequently described, mainly after second dose. Here, we report our findings in four male patients consistent with acute myocarditis at our Institutional Hospital; all four had recently received a second-dose mRNA vaccine. All presented with acute chest pain associated with biomarker evidence of myocardial injury and were hospitalized. None of them had a previous history of SARS-CoV2 infection. All of them showed markedly abnormal EKG findings with diffuse ST segment elevation and laboratory tests revealed elevated high-sensitivity (hs) troponin T levels and C-reactive protein with no peripheral eosinophilia. All patients underwent nasopharyngeal swabbing and the specimens were tested for common respiratory viruses by RT-PCR and resulted all negative. All patients underwent CMR scan during hospitalization. The hospital course was benign for all patients without evidence of arrhythmias or heart failure, in all cases we performed a conservative treatment with nonsteroidal anti-inflammatory drugs and colchicine with progressive normalization of troponin levels before discharge. Our cases presented features of acute myocarditis with a temporal association with the mRNA Covid-19 vaccination, in absence of other apparent causes (in fact none had viral prodromes) nor COVID-19 infection in the prior year. Several reports in the past months had suggested a possible association between the mRNA Covid-19 and myocarditis, most of the cases presenting in young males, after the second dose and with a favourable course. Thus, given the potential risk of cardiac involvement after SARS-CoV-2 infection even in younger adults, the risk-benefit decisions favours vaccination for population immunity. Despite this, the potential mechanisms of SARS-CoV-2 vaccine-related myocarditis seem different from the previously described eosinophilic myocarditis after smallpox vaccination remain unclear and vaccine adverse event reporting remains of high importance. Figure 1 shows one acute MRI scan with STIR, T2-map and LGE in short-axis and apical four-chamber view.
555 Torsade-de-pointes electrical storm late after treatment with hydroxychloroquine and azithromycin for COVID-19
Authors: Bricoli Serena , Bonura Rosario , Cacciola Giovanna , Zardini Marco
Published: December 2021

A 78-year-old woman was admitted to our hospital due to multiple brief episodes of transient loss of consciousness. She was recently hospitalized elsewhere for SARS-CoV-2 infection and she had been discharged two days before. During the previous hospitalization she had been treated with hydroxychloroquine 400 mg twice daily on Day 1, followed by Hydroxychloroquine 400 mg daily together with azithromycin 500 mg daily for 7 days, leading to symptomatic resolution and two consecutive negative RT-PCR tests at discharge. Her medical history included dilated cardiomyopathy and in 2017 she underwent CRT-D implantation for primary prevention; over the past 3 years, she did not experience any ICD intervention. Her home therapy included amiodarone, bisoprolol, warfarin, and trazodone. Baseline ECG obtained 6 month before admission is shown in Figure 1, Panel A. On admission, her ECG showed sinus bradycardia with biventricular pacing and significant QT prolongation (i.e. 640 ms, Figure 1 B). On day 2 of hospitalization, she reported multiple brief episodes of transient loss of consciousness. An interrogation of her device revealed 27 torsade-de-pointes episodes in a 48-hour period, treated with 11 shocks. All episodes were preceded by a variable period of bigeminal rhythm due to one or two premature ventricular beats coupled to the prolonged QT segment of the preceding basic beat in a ‘short-long-short’ sequence (Figure 2). The patient experienced a torsade-de-pointes TdP during COVID-19 disease. She had multiple concomitant factors for QT prolongation (TISDALE SCORE 13): mainly, female sex, cardiac disease, inflammation, electrolyte imbalances and multiple QT-prolonging drugs. Amiodarone and bisoprolol were subsequently stopped and potassium and magnesium were supplemented, with rapid resolution of torsade-de-pointes. No more episodes of TdP were detected after two weeks of hospitalization. The remote monitoring assessment of her device did not show any further episodes during subsequent follow-up. To our best knowledge, this is the first ICD-documented report of a TdP electrical storm in a COVID-19 patient, treated with HCQ/AZT, who had multiple concomitant factors for QT prolongation. 555 Figure 1
399 CMR prevalence of subclinical myocardial damage in non-hospitalized COVID-19 patients: are we looking for a needle in a haystack?
Authors: Del Monaco Guido , Bombace Sara , Stankowski Kamil , Lisi Costanza , Mastinu Sara , Monti Lorenzo , Francone Marco
Published: December 2021

Aims

Subclinical myocardial damage is not uncommon in COVID-19 patients, likely reflecting a combination of direct viral toxicity with the activation of an uncontrolled autoimmune response usually developing during the cytokine storm phase. Whilst myocardial involvement in hospitalized patients has been extensively described in literature, no data are currently available for non-hospitalized individuals. Present study aimed to explore prevalence and impact on patients’ management of myocardial damage detected with CMR, in a cohort of consecutive non-hospitalized SARS-CoV-2 infection patients.

Methods and results

We conducted a single centre prospective observational study on 31 consecutive patients with previous COVID-19 who underwent CMR between October 2020 and June 2021 without requiring hospital admission. Myocarditis was defined by CMR according to the revised Lake Louise Criteria (LLC), if at least one criterion was positive: T2-based marker for myocardial oedema and T1-based marker for associated myocardial injury. Our patients’ cohort included 31 individuals with a mean age of 42.5 ± 17.4 years (20 males; 64.5%) with mean follow-up time of 365.8 ± 89 days between first positive PCR and last clinical evaluation. CMR evidence of cardiac involvement was observed in six patients (19.3%)—including two acute (of which one with pericardial inflammation), one subacute and three healed myocarditis. CMR abnormalities were associated with a higher percentage of palpitations (83% vs. 24%, P = 0.013) and chest pain (66% vs. 16%, P = 0.026) during the active phase of COVID-19. In all CMR positive cases, a tailored therapeutic approach was established consisting with the administration of cardioactive therapy with beta-blockers. All cases were uneventful during the follow-up period.

Conclusions

Our data showed a 19.3% prevalence of unexpected/subclinical myocardial involvement in a cohort of 31 consecutive non-hospitalized patients with previous SARS-CoV-2 infection. CMR findings were retrospectively associated with cardiac symptoms during the acute phase and yielded a change in clinical and therapeutic management in all positive cases. A better knowledge of symptomatic course of COVID-19 could help physicians to adequately select individuals in which CMR may show signs of cardiac damage.
148 ECG abnormalities in COVID-19 pneumonia: acute pericarditis, silent cad, or both? A case report
Authors: Franco Erica , Visconti Massimiliano , Taglialatela Vittorio , Panella Silvana , Rovera Chiara , Conti Valentina , Iancu Dana Miruna , Raineri Michele , Corgnati Giuditta , Marangoni Ludovica , Picardi Elisa , Solaro Cristina , Moretti Claudio
Published: December 2021

Aims We report the case of a hypertensive 70 year-old man, who presented to the Emergency Department (ED) with fever, dry cough, malaise, dyspnoea. A nasopharyngeal swab for SARS-CoV-2 test was done, being positive.

Methods and results Chest TC demonstrated ground glass bilateral pneumonia. Laboratory test showed WBC 10680/mmc, CRP 20 mg/l, TnT 0.03 ng/l, NTproBNP 147 ng/l. The liver and kidney function were within normal values. ECG was normal. He was treated with high flow oxygen (cPAP), enoxaparin, dexamethasone, doxycycline. After an initial improvement, dyspnoea got worse in 8th day, with the evidence of a new rise of inflammatory markers (PCR 95 mg/l, IL6 49 pg/ml) and the clinical new onset of cardiac rubbings on medical examination. The ECG revealed a sinus rhythm with T wave inversion everywhere. TnT remained normal. Echocardiography revealed a normal ventricular function, without segmentary alterations, absence of valvular disease. A mild pericardial effusion was evidenced, without signs of tamponade. We treated the patient with tocilizumab, after exclusion of other active infective foci. The clinical response was good, the patient was progressively weaned by oxygen and he was discharged asymptomatic. After 15 days, for ECG alterations persistence, despite no signs of ACS, a Coronary TC was done and a subcritical multivessel coronary artery disease was demonstrated: a subcritical IVA stenosis and a calcific MO.

Conclusions In conclusion we report a successful treatment of COVID pneumonia likely complicated by acute pericarditis, and we observe that in these patients hypoxemia and cytochine storm possibly bring out silent vascular diseases, otherwise neglected.
659 Myocardial infarction and ischaemic stroke in a COVID-19 patient: nothing happens by chance
Authors: Ianniciello Antonio , Attena Emilio , Uccello Ambra , Caso Valentina Maria , Golino Paolo , Russo Vincenzo
Published: December 2021

A 68-years-old man, affected by arterial hypertension in treatment with angiotensin-receptor blocker (cardesartan 32 mg), was admitted to emergency department for fever and dyspnoea. The molecular swab for SARS-CoV-2 was positive. Chest CT showed bilateral interstitial pneumonia with Chung severity score index 15/20. The laboratory examinations showed: PCR 21 mg/dl, IL-6 17 pg/ml, d-dimer 374 ng/ml, lymphopenia, glycaemia 218 mg/dl, total cholesterol 245 mg/dl. At COVID-19 diagnosis he started the following therapy: Azithromycin 500 mg once a day, Methylprednisolone 20 mg twice a day, Remdesivir 200 mg once a day, Enoxaparin 6000 UI twice a day, Insulin Lispro 6/8/8 UI three times a day, High FlowNasal Cannula (FiO2 45%). No lipid-lowering therapy was prescribed. During the hospitalization, the patient experienced a progressive improvement in clinical and laboratory parameters. On the 28th day, there was a sudden worsening of dyspnoea with evidence of ST-elevation in DI, aVL, V2–V6 leads. A primary percutaneous coronary intervention at COVID-19 HUB hospital (2.9 km away) was required. Because of massive demand for emergency vehicles, the patient was admitted to the Chat Lab 3 h and 23 min later. Due to evidence of critical stenosis of the proximal and intermediate left anterior descending artery, a PTCA with stenting was performed. 12 h later, the patient developed left hemiplegia (NIHSS score: 7). The brain CT revealed an acute right frontal ischaemic lesion; no indication to fibrinolysis was given by the consultant neurologist. Our case report describes the rare concomitance of two thrombotic events in a COVID-19 patient with many cardiovascular risk factors, offering the opportunity to underline the need of their appropriate treatment during the hospitalization for SARS-CoV-2 infection. Moreover, a dedicated treatment pathways should be provided for COVID-19 patients in order to ensure the timely and correct application of the protocols suggested by the international guidelines. 659 Figure 1ECG performed at the onset of acute dyspnoea.659 Figure 2Critical stenosis on LAD and subcritical stenosis on first and second obtuse marginal arteries.
429 Incidence and management of adverse events among COVID-19 vaccination receipts with Brugada syndrome. Results from a multicentre-prospective European registry
Authors: Cetera Rosa , Santoro Francesco , Gianfrancesco Domenico , D’Arienzo Girolamo , Bartolomucci Francesco , Pellegrino Pierluigi , Brunetti Natale Daniele
Published: December 2021

Aims

Patients with Brugada syndrome have an increased risk of life-threatening arrhythmias when experience fever. Therefore, a prompt treatment of non-steroidal anti-inflammatory drugs (NSAI) is suggested in these patients. COVID-19 vaccination can be associated with fever in about 20% of patients. The aim of the study is to evaluate the incidence and management of adverse events within 48 h from COVID-19 vaccination among Brugada patients.

Methods and results

Eighty patients were enrolled from a prospective registry involving four European hospitals with a dedicated inherited disease ambulatory. Cardiological follow-up was performed within one month from vaccination. Mean age was 47 ± 17 years, 80% (num = 63) were male. Prevalence of Brugada types 1, 2, and 3 was as follows: 25% type 1, 39% type 2, and 24% type 3. Twenty-six percent of patients had an implantable cardioverter defibrillator (ICD). Within in 48 h from vaccination, 35% (num = 28) of patients experienced joint paint, 19% (num = 15) fever and 4% (num = 3) chest pain. In 8 out of 15 fever episodes body temperature was ≥38 degrees and treated with NSAI drugs. No patients had syncope or fatigue episodes and no arrhythmic episodes were recorded in patients with ICD.

Conclusions About 20% of patients experienced fever after Covid-19 vaccination but no patient experienced life-threatening arrhythmias. Careful evaluation of body temperature and administration of NSAI in case of temperature higher than 38 is suggested.
764 Prevalence and clinical implications of cardiac involvement in individuals with paucisymptomatic SARS-CoV-2 infection
Authors: Trancuccio Alessandro , Mazzanti Andrea , Kukavica Deni , Arnò Carlo , Sturla Matteo , Marino Maira , Bloise Raffaela , Napolitano Carlo , Monti Lorenzo , Priori Silvia G.
Published: December 2021

Aims

Myocardial involvement has been reported in SARS-CoV-2 infection, especially in hospitalized patients during the acute phase of the disease. However, the exact prevalence and the clinical implications of cardiac involvement in young individuals with paucisymptomatic SARS-CoV-2 infection are debated.

Methods and results

We gathered data on 100 young patients with previous paucisymptomatic SARS-CoV-2 infection, not undergoing hospitalization and without previous diagnosis of structural heart disease, who underwent cardiological evaluation in our clinic at IRCCS ICS Maugeri (Pavia, Italy). Results were validated in an external cohort of 28 patients who underwent cardiac magnetic resonance (MRI) at Humanitas Research Hospital (Rozzano, Italy). The study population included 100 patients with previous paucisymptomatic SARS-CoV-2 infection: 60 (60%) males; median age 36 years (IQR: 22–50 years); median time after SARS-CoV-2 infection 181 days (IQR: 76–218 days). At the cardiological evaluation, 31/100 (31%) of patients referred cardiological symptoms, including dyspnoea, palpitations, chest pain or syncope. Overall, 26/100 (26%) patients showed on or more of the following instrumental alterations at first level assessment: 4/100 (4%) increase of TnI; 7/100 (7%) electrocardiographic abnormalities, 12/100 (12%) ventricular arrhythmias, and 11/100 (11%) echocardiographic abnormalities. Of 32 patients who underwent cardiac MRI, myocardial involvement was detected in 6/32 (19%) patients (Figure 1), similarly to what was observed in the validation cohort [54% males; median age 47 years (IQR: 26–55 years); myocardial involvement at MRI 4/28, 14%]. Furthermore, the proportion of patients with myocardial involvement was significantly higher in patients with first-level cardiac alterations (6/18, 28%) as compared with patients without cardiac alterations at first-level examination (0/14, 0%, P = 0.024). When analysing possible predictors for the occurrence of cardiac involvement at the MRI, documentation of ventricular arrhythmias at Holter ECG or exercise test was associated with an 87-fold higher probability of cardiac involvement at the MRI (OR: 87.3; 95% CI: 4.0–1914.3; P < 0.001).

Conclusions

Around 15–20% of patients with paucisymptomatic SARS-CoV-2 infection exhibit cardiac involvement documented at the cardiac MRI after a mean of 6 months from the onset of the disease. The presence of instrumental alterations detected with first level diagnostic tests, and in particular the documentation of ventricular arrhythmias at the 24 h-Holter ECG or at the exercise stress test, is a powerful predictor of myocardial involvement.
220 Electrocardiographic findings and mortality in COVID-19 patients hospitalized in different clinical settings
Authors: Mele Marco , Tricarico Lucia , Vitale Enrica , Favia Andrea , Croella Francesca , Alfieri Simona , Corbo Maria Delia , Mango Federica , Casavecchia Grazia , Brunetti Natale Daniele
Published: December 2021

Aims

12-lead electrocardiogram (ECG) still represents the first line approach for cardiovascular assessment even in patients with COVID-19. We therefore sought to describe and compare ECG findings in three different hospital settings: intensive care unit (ICU) (invasive ventilatory support), respiratory care unit (RCU) (non-invasive ventilatory support) and Covid-19 dedicated internal medicine unit (IMU) (oxygen supplement with or without high flow).

Methods and results

We retrospectively analysed the 12-lead ECGs of 1124 consecutive patients hospitalized for respiratory distress and COVID-19 in a single III level hospital. Age, gender, main clinical data and in-hospital survival were recorded. 548 patients were hospitalized in IMU, 361 in RCU, 215 in ICU. Arrhythmias in general were less frequently found in RCU (16% vs. 26%, P < 0.001). Deaths occurred more frequently in ICU patients (43% vs. 20–21%, P < 0.001). After pooling predictors of mortality (age, intensity of care setting, heart rate, ST-elevation, QTc prolongation, Q-waves, right bundle branch block, and atrial fibrillation), the risk of in-hospital death can be estimated by using a derived score. Three zones of mortality risk can be thus identified: <5%, score <5 points; 5–50% score 5–10, and >50%, score >10 points. The accuracy of the score assessed at ROC curve analysis was 0.791.

Conclusions

ECG differences at admission con be found in COVID-19 patients according to different clinical settings and intensity of care. A simplified score derived from few clinical and ECG variables may predict in-hospital mortality with a good accuracy.
112 Safety and biochemical efficacy of sodium–glucose cotransporter 2 inhibitors based on cardiovascular risk profile and volume status in a real-world diabetic population
Authors: Gitto Mauro , Kotinas Alexios , Terzi Riccardo , Oliva Angelo , Zagoreo Jorgele , Reimers Bernhard , Stefanini Giulio G , Mirani Marco , Favacchio Giuseppe , Condorelli Gianluigi , Panico Cristina
Published: December 2021

Aims

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have become a first-line cardiovascular medication. However, their potential side effects still limit a widespread use in real-world clinical practice. Further, there is uncertainty about the mechanisms mediating SGLT2i-associated cardiovascular benefit.

Methods

We performed a retrospective analysis on consecutive diabetic patients who were prescribed a SGLT2i in a tertiary referral centre. Patients who completed at least 1 year of treatment were included in the data analysis. Changes in glycated haemoglobin, weight and haematocrit were evaluated and compared across two cardiovascular risk categories, defined through the inclusion criteria of three large randomized clinical trials. Additionally, a modified clinical score (mH2FPEF) was applied to detect the probability of heart failure with preserved ejection fraction (HFpEF).

Results

Of the 459 patients screened from 2015 to 2020, 312 completed 1 year of treatment (68.0%), 92 interrupted the treatment prematurely (20.0%) and 55 were lost to follow-up (12.0%). The most common causes of drug discontinuation were genital or urinary tract infections (9.4%) and poor glycaemic control (5%). At 1 year, a significant reduction in glycated haemoglobin concentration (−0.6 ± 1.4%, P < 0.001) and body weight (2.4 ± 4.6 Kg, P < 0.001) was observed and was comparable between patients at high vs. low cardiovascular risk. Haematocrit increase at 1 year (2.3 ± 3.3%, P < 0.001) was more marked in patients with high cardiovascular risk and low baseline haematocrit. Among patients with no established heart failure (N = 295), 156 (52.9%) had >50% probability of HFpEF (mH2FPEF ≥3).

Conclusions

In a real-world population of diabetic patients, SGLT2i were well-tolerated at 1 year and led to improved glycaemic control and weight loss. Haematocrit increase was more consistent in patients with high cardiovascular risk and signs of fluid overload, indicating the potentially beneficial role of euvolemic restoration. More than half of these diabetic patients had a high likelihood of unrecognized HFpEF.
683 Cor in memoria posterorum: role of familial screening in sudden death syndrome
Authors: Chiti Chiara , Parisi Vanda , Graziosi Maddalena , Biagini Elena
Published: December 2021

A 14-year-old boy suddenly died during a school lesson. His familial history was negative for sudden cardiac death and no comorbidities were reported. As part of Emilia Romagna regional network for sudden cardiac death, the heart was examined at our Cardiovascular Pathology Unit. The molecular autopsy revealed extensive lymphocytic macrophage left ventricle myocarditis (infero-lateral and anterior wall) in various evolutive stages. Genetic testing with next-generation sequencing was performed on DNA isolated from explanted heart samples (178 candidate genes for channelopathies and cardiomyopathies were analysed) and it showed a frameshift pathological mutation in the filamine C gene (FLNC c.8034delC p. Cys2679fsTer6) which induces protein premature termination. In order to screen family members, we evaluated the father, 53-year-old, asymptomatic and with an unremarkable cardiology history. The ECG showed sinus rhythm, HR 60 b.p.m., normal atrioventricular conduction, QRS fragmentation and negative T waves in the inferior leads. The echocardiogram revealed left ventricle mild dilation (79 mL/m2) with global hypokinesia (EF 45%), while right ventricle was normal for size and kinetics. A cardiac MRI confirmed left ventricular dilation and hypokinesia with diffuse LGE with circumferential mesocardial distribution mainly in the middle-baseline site, which reflected structural damage (fibrosis). The 24-h Holter ECG did not record arrhythmias. The genetic test was then performed and the same FLNC frameshift mutation was identified. We thus suspected familial arrhythmogenic cardiomyopathy involving left ventricle with pathological filamine C mutation and an ICD was recommended. Other family members had no pathological findings. Filamine C mutations are associated with many type of cardiomyopathy. A possible association between some mutated variants and certain subtypes of cardiomyopathy has been highlighted. In particular, the frameshift variant is associated with an increased arrhythmic risk, particularly when dilated forms are considered. Recent studies have identified a correlation with arrhythmogenic cardiomyopathy, although the role of these mutated variants has not yet been fully defined. This clinical case underlines the importance of multidisciplinary approach in cases of sudden cardiac death, consisting of autopsy, genetic and clinical evaluation, in order to identify any forms of familial cardiomyopathy and activate a systematic screening in family members with important prognostic and therapeutic implications. Data about our regional structural network for sudden cardiac death will also be shown.
14 Telomerase and myocardin co-expressing mesenchymal cells increase survival and induce cardiac and vascular markers in cardiac stromal cells undergoing simulated ischemia/reperfusion
Authors: Madonna Rosalinda , Guarnieri Simone , Kovacshazi Csenger , Gorbe Aniko , Giricz Zoltan , Geng Yong-Jian , Mariggiò Maria Addolorata , Ferdinandy Peter , De Caterina Raffaele
Published: December 2021

Aims

Cardiac stromal cells (CSCs) contain a pool of cells with supportive and paracrine functions. Various types of mesenchymal stromal cells (MSCs) can influence CSCs in the cardiac niche through their paracrine activity. Ischemia/reperfusion (I/R) leads to cell death and reduction of the paracrine activity of CSCs. The forced coexpression of telomerase reverse transcriptase (TERT) and myocardin (MYOCD), known to potentiate anti-apoptotic, pro-survival and pro-angiogenic activities of MSCs isolated from the adipose tissue (AT-MSCs), may increase CSC survival, favouring their paracrine activities. To investigate the hypothesis that CSCs feature improved resistance to simulated I/R (SI/R) and increased commitment toward the cardiovascular lineage when preconditioned with conditioned media (CM) or extracellular vesicles (EV) released from AT-MSCs overexpressing TERT and MYOCD (T/M AT-MSCs).

Methods

Murine CSCs were isolated with the cardiosphere (CSps) isolation technique.

Results

T/M AT-MSCs and their secretome improved spontaneous intracellular calcium changes and ryanodine receptor expression in aged CSps. The cytoprotective effect of AT-MSCs was tested in CSCs subjected to SI/R. SI/R induced cell death as compared to normoxia (28 ± 4 vs. 10 ± 3%, P = 0.02). Pre-treatment with CM (15 ± 2, P = 0.02) or with the EV-enriched fraction (10 ± 1%, P = 0.02) obtained from mock-transduced AT-MSCs in normoxia reduced cell death after SI/R. The effect was more pronounced with CM (7 ± 1%, P = 0.01) or the EV-enriched fraction (2 ± 1%, P = 0.01) obtained from T/M AT-MSCs subjected to SI/R. In parallel, we observed lower expression of the apoptosis marker cleaved caspase-3 and higher expression of cardiac and vascular markers eNOS, sarcomeric α-actinin and cardiac actin.

Conclusions

The T/M AT-MSCs secretome exerts a cytoprotective effect and promotes development of CSCs undergoing SI/R towards a cardiovascular phenotype.
62 Biventricular evaluation of gliflozines effects in chronic heart failure patients function (begin-HF study): an international registry
Authors: Correale Michele , Mazzeo Pietro , Petroni Renata , Coiro Stefano , Antohi Elena-Laura , Monitillo Francesco , Leone Marta , Triggiani Marco , Dungen Hans-Dirk , Sarwar Chaudhry M. S. , Nodari Savina
Published: December 2021

Aims

Sodium glucose cotransporter type 2 (SGLT2) inhibitors represent a new class of hypoglycemic agents for type 2 diabetes mellitus (T2DM), which act independently of insulin to selectively inhibit renal glucose reabsorption, thereby increasing urinary excretion of glucose. Several studies have demonstrated the cardioprotective effects of SGLT2-i in patients with heart failure (HF), with and without diabetes mellitus. It is also unknown whether these SGLT2is-associated benefits are associated with the amelioration of left or right ventricular function in patients affected by HF with T2DM. Evaluate the effect of SGLT2 inhibitors on left and right ventricular function by conventional and advanced echocardiographic parameters, focusing on speckle tracking echocardiography, in patients with HF and T2DM.

Methods and results

BEGIN-HF is an international multi-centre registry enrolling outpatients affected by HF and T2DM. Inclusion criteria are HbA1c> 6.5%, eGFR [MDRD] > 45 ml/min/1.73 m2, age > 18 years, FE < 50%. Exclusion criteria are type 1 diabetes mellitus (T1DM), previous amputation surgery, recurrent urinary tract infections. For each patient medical history, clinical and biochemistry data will be collected, starting treatment with SGLT2 inhibitors will be included. All patients will undergo conventional, TDI, and strain echocardiography in an ambulatory setting, at the enrollement and after 3 and 6 months. The patients will be divided in the two subgroup for analysis (patients starting SGLT2i therapy and patients no starting SGLT2i). The primary endpoint will be the improvement of LV systolic and right ventricular systolic function as assessed by conventional, TDI and myocardial deformation speckle tracking parameters. A univariate and multivariate analysis will be performed to search for predictors of improvement of systolic function.

Conclusions

This is the first international multicentre registry evaluating biventricular function by conventional and advanced echocardiography in patients with HF and T2DM starting and no-starting SGLT2i therapy.
155 Effects on sacubitril/valsartan on natriuretic peptides in patients with a reduced ejection fraction
Authors: Lamaida Norman , Cerciello Antonio
Published: December 2021

Aims

The PARADIGM-HF trial proved the superiority of sacubitril/valsartan (Sa/Va) vs. enalapril in reducing mortality and hospitalization for heart failure (HF). Sacubitril/valsartan, new drug used in treatment of heart failure with reduced systolic function (HFrEF) has recently been shown to improve tolerance to exercise and cardiovascular performance.

Methods and results

We prospectively enrolled 40 outpatient patients with HFrEF with indication for therapy with sacubitril/valsartan and subjected to serial controls with blood tests, echocardiogram before and during gradual optimization of therapy, with the aim of evaluating the effects of the drug on left ventricular remodelling. We studied 40 patients treated with sacubitril/valsartan for at least 3 months. After a mean follow-up of 120 ± 40 days, 95% of patients reached the maximum dose of the drug without major side effects. The ejection fraction increased while end-diastolic and end-systolic volumes of the left ventricle decreased. We also observed a significant reduction in NT-proBNP values without significant worsening of renal function or hyperkalaemia. There NYHA functional class has improved with a positive impact on the prognosis of heart failure at 2 years (P = 0.006).

Conclusions

In our population, medium-term treatment with sacubitril/valsartan demonstrated a favourable effect on left ventricular remodelling and functional status, confirming the data of previous clinical trials in real life. One more follow-up long and a larger population will help confirm these to confirm these positive effects of the drug on patients with HfrEF.
359 Transient vs. persistent improved ejection fraction in non-ischaemic dilated cardiomyopathy
Authors: Manca Paolo , Stolfo Davide , Merlo Marco , Gregorio Caterina , Cannatà Antonio , Ramani Federica , Nuzzi Vincenzo , Lund Lars , Savarese Gianluigi , Sinagra Gianfranco
Published: December 2021

Aims

The recent definition of heart failure with improved ejection fraction (HFimpEF) outlined the importance of the longitudinal assessment of left ventricular ejection fraction (LVEF). However, long-term progression and outcomes of this subgroup are poorly explored. We sought to assess the LVEF trajectories and the correlations with outcome in non-ischaemic dilated cardiomyopathy (NICM) with improved ejection fraction (impEF).

Methods and results

Consecutive NICM patients with baseline LVEF ≤40% enrolled in the Trieste Heart Muscle Disease Registry with ≥1 LVEF assessment after baseline were included. ImpEF was defined as a baseline LVEF ≤40%, a ≥ 10 point increase from baseline LVEF, and a second measurement of LVEF >40%. Transient impEF was defined by the documentation of recurrent LVEF ≤40% during follow-up. The primary endpoint was a composite of all-cause death, heart transplantation and left ventricular assist device (D/HT/LVAD). Among 800 patients, 460 (57%) had impEF (median time to improvement 13 months). Higher heart rate, smaller left atrium, absence of severe mitral regurgitation and shorter duration of disease were associated with impEF. ImpEF was independently associated with lower risk of D/HT/LVAD (HR: 0.36; 95% CI: 0.27–0.48; P < 0.001). Transient impEF was observed in 189 patients (41% of the overall impEF group) and was associated with higher risk of D/HT/LVAD compared with persistent impEF at multivariable analysis (HR: 2.54; 95% CI: 1.60–4.04).

Conclusions

In NICM, we observed a 57% rate of impEF. However, recurrent decline in LVEF was observed in ≈40% of impEF patients and it was associated with an increased risk of D/HT/LVAD.
362 Trends in the use/non-use of guideline-directed medical therapy in non-ischaemic dilated cardiomyopathy with improved ejection fraction
Authors: Santi Giovanni , Manca Paolo , Nuzzi Vincenzo , Venturelli Francesco , Ramani Federica , Barbati Giulia , Gregorio Caterina , Stolfo Davide , Merlo Marco , Sinagra Gianfranco
Published: December 2021

Aims

Guideline-directed medical therapy (GDMT) is associated with significant improvement of left ventricular function in an important fraction of patients with non-ischaemic dilated cardiomyopathy (NICM), and the recent definition of heart failure with improved ejection fraction (HFimpEF) highlights the importance of longitudinal assessment of left ventricular ejection fraction (LVEF); however, little is known about the long-term outcome of GDMT downtitration in patients with NICM who develop HFimpEF. We sought to assess the functional and prognostic impact of GDMT downtitration in this subgroup.

Methods and results

All consecutive NICM patients enrolled from 1991 to 2018 in the Trieste Heart Muscle Disease Registry with baseline LVEF ≤40% and with ≥1 LVEF assessment after baseline were included. ImpEF was defined as a baseline LVEF ≤40%, a ≥ 10 point increase from baseline LVEF, and a second measurement of LVEF >40%. GDMT downtitration was defined as any dose reduction or drug withdrawal of renin-angiotensin system inhibitors (RASi) or beta-blockers (BB). The outcome measures were a loss of impEF criteria, a composite of all-cause death and heart transplantation (ACD/HTx), a composite of HF hospitalization, heart transplantation and left ventricular assist device (HFH/HTx/LVAD), and a composite of sudden death and major ventricular arrhythmias (SD/MVA). The prognostic role of GDMT downtitration was assessed with Kaplan–Meier analysis and curves of cumulative incidence, considering GDMT downtitration, loss of impEF, and the composites of outcome as time-dependent variables. Among 452 NICM patients with impEF, 186 (41.2%) downtitrated GDMT (median time to downtitration 35 months). Loss of impEF criteria occurred in 186 patients (median time to loss of impEF 51 months). While no significant differences in terms of ACD/HTx, HFH/HTx/LVAD, or SD/MVA among those who downtitrated GDMT and those who didn’t were observed, the population that downtitrated GDMT had a higher cumulative incidence of loss of impEF (P < 0.001).

Conclusions

In NICM patients who develop impEF, we observed a ≈ 40% rate of recurrent decline of LVEF. GDMT downtitration seems to be associated with this functional deterioration, although no differences in terms of major cardiovascular outcomes emerged.
379 Contemporary use of guideline directed medical therapy in dilated cardiomyopathy: therapeutic optimization and prognostic benefits
Authors: Venturelli Francesco , Nuzzi Vincenzo , Manca Paolo , Santi Giovanni , Barbati Giulia , Gregorio Caterina , Stolfo Davide , Merlo Marco , Sinagra Gianfranco
Published: December 2021

Aims

Therapy with antineurohormonal drugs at target doses has a prognostic benefits in heart failure with reduced ejection fraction. Dilated cardiomyopathy (DCM) represents a particular setting where the possible benefit of target doses of antineurohormonal drugs is unexplored.

Methods and results

All patients enrolled from 1/1/1992 to 1/3/2020 in the Trieste Muscle Heart Disease register affected by DCM with data on the dosage of therapy available both enrollment and at follow-up visit (i.e., 6–12 month) were included. The population was divided according to the percentage of recommended dose prescribed (0–49%, 50–99%, 100%) of both renin-angiotensin system inhibitors (RASi) and beta blockers (BB). A composite of death/heart transplant/hospitalization for heart failure was considered as the primary endpoint; a composite of sudden cardiac death/major ventricular arrythmias/defibrillator intervention was evaluated as a secondary endpoint. Prognostic associations were explored with uni- and multivariate analyses, Cox regressions, Kaplan–Meier, cumulative incidence curves and propensity score matching. 826 patients were included. At baseline 789 (96%) were taking a RASi and 627 (76%) a BB. The target dose of RASi was prescribed in 29% and 36% of patients at enrolment and at follow-up visit, respectively. The percentage of patients taking the maximum recommended dose of BB was 10% at baseline and 17% after optimization. Predictors of reaching target dose for RASi were BMI < 25 kg/m2, male sex [HR: 1.798 (95% CI: 1.073–3.012), P = 0.026] and higher systolic blood pressure [HR per mmHg 1.038 (95% CI: 1.025–1.051), P < 0.001]. Target dose predictors of BB were age [HR per year 0.527 (95% CI: 0.347–0.802), P = 0.003] and highest systolic blood pressure [HR per mmHg 1.024 (95% CI: 1.013–1.035), P < 0.001]. After adjustment target dose of RASi or BB did not show a significant association with the risk of primary outcome occurrence compared to those taking less than 50% (P = 0.550 for RASi and P = 0.921 for BB). The incidence of arrhythmic events was significantly lower in patients taking 100% of recommended dose of BB compared to those taking less than 50% (P = 0.009), after adjustment for confounders. The target dose of RASi was not associated with an arrhythmic events risk change (P = 0.688).

Conclusions

In DCM a significant number of patients do not tolerate maximal therapy doses, mainly due to hypotension. The achievement of the target dose of RASi and BB, after adjustment for confounders had a neutral effect on the incidence of heart failure-related events. Uptitration of BB to the recommended dose has a strong protective effect on arrhythmic events.
520 A possible easy way to predict response to cardiac resynchronization therapy: the role of QRS index
Authors: Coppola Giuseppe , Novo Giuseppina , Prezioso Amedeo , Bonnì Enrico , Madaudo Cristina , Campo Francesco , Sucato Vincenzo , Ciaramitaro Gianfranco , Galassi Alfredo Ruggero , Corrado Egle
Published: December 2021

Several studies have evaluated the role of QRS duration or QRS narrowing as predictor of response to cardiac resynchronization therapy (CRT) in order to reduce non-responders. However, their results have been conflicting. The aim of our study was to determine the association between the relative change in QRS narrowing index (QI) and clinical outcome and prognosis in patients who underwent CRT implantation. We included 115 patients in whom a CRT device was implanted in accordance with current guidelines. Baseline clinical variables, echocardiographic parameters, and pharmacological therapies were included. QRS duration before and after CRT implantation and QI [(pre implant QRS duration—QRS duration during CRT)/pre implant QRS duration × 100] were measured. After 6 months, a significant improvement in all echocardiographic parameters was observed. In 103 (90%) patients, LVESV decreased by 10% or more. QI was significantly related to reverse remodelling (r = +0.19; 95% CI: 0.006–0.35, P = 0.049). The cut-off value of QI that predicted best LV reverse remodelling after 6 months of CRT was 12.25% (sensitivity = 65.5%, specificity = 75%, area under the curve = 0.737, P = 0.001). An improvement in their HF clinical composite score at 12 months was found in 23 patients (21%). Considering the improvement in NYHA class, of the 73 patients with QI > 12.25%, 34 (46.5%) had a reduced NYHA class at 12 months post implantation. A statistically significant difference was found between patients with a QI < 12.25%, and those with a QI > 12.25%, in terms of NYHA class worsening (P 0.04). Also a statistically significant difference was found between the mean of the QI of patients who died from cardiovascular causes and patients who died of other causes. We have also investigated the possible sex differences related to QI; women with QI > 12.25% had a statistically significant greater improvement in LVEF at follow-up than men with QI > 12.25% (P 0.03). Patients with a larger decrease in QRSd after CRT initiation showed greater echocardiographic reverse remodelling and better outcome from death or cardiovascular hospitalization. Even if larger studies are needed, QI seems to be an easy-to-measure variable that could be used or evaluated to predict CRT response.