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Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) represents a heterogeneous clinical conundrum accounting for about 6%–8% of all acute MI who are referred for coronary angiography. Current guidelines and consensus documents recommend that these patients are appropriately diagnosed, uncovering the causes of MINOCA, so that specific therapies can be prescribed. Indeed, there are a variety of causes that can result in this clinical condition, and for this reason diagnostic cardiac imaging has an emerging critical role in the assessment of patients with suspected or confirmed MINOCA. In last years, different cardiac imaging techniques have been evaluated in this context, and the comprehension of their strengths and limitations is of the utmost importance for their effective use in clinical practice. Moreover, recent evidence is clearly suggesting that a multimodality cardiac imaging approach, combining different techniques, seems to be crucial for a proper management of MINOCA. However, great variability still exists in clinical practice in the management of patients with suspected MINOCA, also depending on the availability of diagnostic tools and local expertise. Herein, we review the current knowledge supporting the use of different cardiac imaging techniques in patients with MINOCA, underscoring the importance of a comprehensive multimodality cardiac imaging approach and proposing a practical diagnostic algorithm to properly identify and treat the specific causes of MINOCA, in order to improve prognosis and the quality of life in these patients.

Background and aims The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for the treatment of cardiogenic shock (CS) may result in left ventricle overload and distension. Percutaneous microaxial flow pump Impella in addition to VA-ECMO (ECPELLA) is an emerging option to overcome these collateral effects. Aim of this study is to assess whether the addition of Impella to VA-ECMO is an effective and safe unloading strategy. Methods and results We performed a systematic literature review of studies comparing ECPELLA vs. ECMO alone in patients with CS. The primary endpoint was early mortality (in-hospital or 30-day mortality). The secondary endpoints were bleeding, need for kidney replacement therapy, haemolysis, infections, and limb ischaemia. A total of 3469 potentially relevant articles were screened and eight retrospective studies including 11.137 patients were selected. There was no significant difference in early mortality (Risk Ratio, RR 0.90, 95% CI 0.78–1.03) between ECPELLA and ECMO. Nevertheless, there was a borderline significant reduction in early mortality with ECPELLA (RR 0.74, 95% CI 0.55–1.00) at sensitivity analysis selectively including studies reporting propensity matched analysis. ECPELLA was associated with increased bleeding (RR 1.45, 95% CI 1.20–1.75), need for kidney replacement therapy (RR 1.54, 95% CI 1.19–1.99), haemolysis (RR 1.71, 95% CI 1.41–2.07) and limb ischaemia (RR 1.43, 95% CI 1.17–1.75) and with a non-significant increase in severe infections (RR 1.26, 95% CI 0.84–1.89), compared with ECMO alone. Conclusion Among patients with cardiogenic shock, ECPELLA is associated with increased complications compared with ECMO. Whether reducing ventricular overload with Impella among patients treated with ECMO reduces early mortality needs to be confirmed by further investigations.

Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery. However, only a few detailed descriptions of the arrhythmia have been reported. We aim to describe the characteristics, outcomes, and variables associated with POAF and to evaluate how posterior pericardiotomy (PP) affects POAF characteristics.In this post hoc analysis of the Posterior left pericardiotomy for the prevention of AtriaL fibrillation After Cardiac Surgery (PALACS) trial, we describe POAF characteristics based on continuous in-hospital telemetry data.Of 420 patients, 103 (24.5%) developed POAF. Median time to onset was 50.3 hours; 70.9% of events occurred within 3 days. Hemodynamic instability and rapid ventricular response occurred in 8.7% and 51.5% of cases, respectively. Most POAF patients received antiarrhythmics (97.1%), 22.3% electrical cardioversion, and 40.8% systemic anticoagulation. Median POAF duration was 24.0 hours; 70.9% of cases resolved within 36 hours. Median POAF burden was 15.9%. All patients were in sinus rhythm at follow-up. POAF was associated with longer hospitalization (7 vs 6 days; P.001), but not increased mortality or morbidity. PP reduced POAF incidence (17.7% vs 31.3%; P = .001), especially after postoperative day 2 (time to POAF onset 41.9 vs 57.1 hours; P = .01). Age was associated with POAF. Female sex, coronary artery bypass grafting, beta blockers, and PP were inversely associated.POAF remains frequent after cardiac surgery. Hemodynamic instability is rare, although rapid ventricular response and need for electrical cardioversion are frequent. POAF burden is significant, and the arrhythmias resolve within 30 days. PP reduces POAF especially after postoperative day 2.

ObjectiveLeft atrial (LA) and left ventricular (LV) mechanics are impaired in patients with atrial functional mitral regurgitation (AFMR), but their prognostic value in this subset of patients remains unknown. The present study aimed to evaluate the association between LA and LV longitudinal strain and clinical outcomes in patients with AFMR.MethodsA total of 197 patients (mean age 73±10 years, 44% men) with at least moderate AFMR were retrospectively identified. LV global longitudinal strain (GLS) and left atrial reservoir strain (LAS) were calculated by two-dimensional speckle tracking echocardiography. All-cause mortality was the primary endpoint of the study. The threshold value of LV GLS (≤16.3%) to identify impaired LV mechanics was defined based on the risk excess of the primary endpoint described with a spline curve analysis.ResultsImpaired LV GLS (≤16.3%) was found in 89 (45%) patients. During a median follow-up of 69 months, 45 (23%) subjects experienced the primary endpoint. Patients with impaired LV GLS (≤16.3%) had a significantly lower cumulative survival rate at 5 years, as compared with patients with LV GLS (>16.3%) (74% vs 93%, pConclusionsIn patients with significant AFMR, the impairment of LV GLS was independently associated with worse outcomes.

Background and aims: Transvenous lead extraction (TLE) has become a pivotal part of a comprehensive lead management strategy, dealing with a continuously increasing demand. Nonetheless, literature about the long-term impact of TLE on survivals still lacking. Given these knowledge gaps, the aim of our study was to analyse very long-term mortality in patients undergoing TLE in public health perspective. Methods: This prospective, single-centre, observational study enrolled consecutive patients with cardiac implantable electronic device (CIED) who underwent TLE, from January 2005 to January 2021. The main goal was to establish the independent predictors of very long-term mortality after TLE. We also aimed at assessing procedural and hospitalization related costs. Results: We enrolled 435 patients (mean age 70 ± 12 years, with mean lead dwelling time 6.8 ± 16.7 years), with prevalent infective indication to TLE (92%). Initial success of TLE was achieved in 98% of population. After a median follow-up of 4.5 years (range 1 month- 15.5 years),150 of the 435enrolled patients (34%) died. At multivariate analysis, death was predicted by: age (≥ 77 years, OR: 2.55, CI: 1.8-3.6, pConclusions: Our study identified three predictors of long-term mortality in a high-risk cohort of patients with a cardiac device infection, undergoing successful TLE. The future development of a mortality risk score before might impact on public health strategy.

Background: There is limited information available regarding evidence of ischemia with no obstructive coronary arteries (INOCA) and quality of life.\ud \ud Purpose: To determine associations between INOCA and self-reported physical, social, and mental health.\ud \ud Methods: We conducted a survey of all members (n = 1579) of the INOCA International patient support group. Current self-reported diagnosis and health measures were collected. Functional capacity was retrospectively estimated using the Duke Activity Status Index (DASI), assessing levels of activities performed prior and after symptom onset.\ud \ud Results: A total of 297 (20.8% response rate, 91% women) reported symptoms of chest pain, pressure, or discomfort in 92.9%. Overall, 34.4% were living with symptoms for ≥3 years before an INOCA diagnosis, and 77.8% were told their symptoms were not cardiac. Estimated functional capacity was higher prior to compared to after symptom onset (8.6 ± 1.8 METs vs 5.6 ± 1.8 METs; P < 0.0001). Most respondents reported an adverse impact of symptoms on their home life (80.5%), social life (80.1%), mental health (70.4%), outlook on life (69.7%), sex life (55.9%), and their partner/spouse relationship (53.9%), while approximately three-quarters reduced their work hours or stopped work completely, 47.5% retired early, and 38.4% applied for disability.\ud \ud Conclusions: INOCA symptoms are associated with adverse physical, mental and social health quality of life. Increased patient awareness, physician recognition and diagnosis, and clinical trials are needed to develop evidence-based guidelines for this increasingly recognized cardiovascular disorder.

Chronic coronary total occlusions (CTO) are considered an emerging predictor of ventricular arrhythmias (VAs), but currently there are few data on arrhythmic outcomes in patients affected by CTO undergoing radiofrequency catheter ablation of VAs. This study sought to evaluate the impact of unrevascularized CTO on the recurrence of VAs after catheter ablation. This was a single-center retrospective study enrolling 120 patients between 2015 and 2020. All patients were admitted for ventricular tachycardia (VT) or high premature ventricular contractions burden (>25% detected by Holter ECG), without evidence of acute coronary syndrome; they underwent coronary angiography, electrophysiology (EP) study, and three-dimensional electroanatomic mapping (3D-EAM) followed by VAs ablation. Twenty-eight patients (23%) of 120 patients showed CTO at coronary angiography. At baseline, the CTO group presented with higher prevalence of hypertension, chronic renal disease, systolic ventricular dysfunction, secondary prevention ICD implantation, and higher rate of LAVA by 3D-EAM compared with the non-CTO group. At a median follow-up of 15 months (range 1–96 months) after catheter ablation, the only independent predictor of VAs recurrence was the presence of moderate to severe left ventricular (LV) dysfunction. Therefore, the presence of CTO does not predict VAs recurrence after catheter ablation, which is instead predicted by LV dysfunction.

Background: The mismatch between in-stent minimum lumen area (sMLA) and reference vessel lumen area, defined as stent underexpansion (SU), could be an important determinant of stent failure. We tested the clinical predictive value of absolute sMLA in comparison to relative SU in the context of the CLI-OPCI (Centro Per La Lotta Contro L’Infarto-Optimisation of Percutaneous Coronary Intervention) project registry. Methods: We retrospectively analyzed end procedural optical coherence tomography findings in 1211 patients (1422 lesions) undergoing percutaneous coronary intervention, assessing the prevalence and magnitude of residual SU and exploring correlation with outcome in comparison with sMLA. Results: In our series, both sMLA and SU were related to vessel size and anatomic lesion complexity. When compared with patients without adverse event at follow-up, those experiencing device-oriented cardiovascular events (composite of cardiac death, target vessel myocardial infarction, target lesion revascularization, and stent thrombosis) showed a lower sMLA (5.6±2.1 versus 6.1±2.1 mm 2 ; P =0.011) but a comparable degree of SU (11.6±14.1% versus 11.2±13.3%; P =0.734). The prespecified cutoff value of sMLA 2 , documented in 23.8% of cases, was confirmed as independent outcome predictor for device-oriented cardiovascular events (hazard ratio [HR], 2.05 [95% CI, 1.5–2.9]) including target lesion revascularization (HR, 2.43 [95% CI, 1.7–3.5]) and stent thrombosis (HR, 3.23 [95% CI, 1.7–6.3]). A residual SU of 10%, 20%, and 30% was observed in 38.0%, 18.2%, and 7.6% of cases, respectively. No grade of residual SU significantly increased the risk of stent failure, unless if an SU >20% was associated with an sMLA 2 (HR, 3.11 [95% CI, 1.7–5.6]). Finally, an association between stent overexpansion (ie, >110%) and device-oriented cardiovascular events was also observed (HR, 1.60 [95% CI, 1.1–2.3]). Conclusions: Final absolute sMLA and not relative SU was associated with an increased risk of stent failure. A variable grade of SU was common, but it resulted in being clinically relevant only when associated with an sMLA 2 .

Background Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) are caused often by destabilization of non-flow limiting inflamed coronary artery plaques. 18F-fluorodeoxyglucose (FDG) uptake with positron emission tomography/computed tomography (PET/CT) reveals plaque inflammation, while intracoronary optical coherence tomography (OCT) reliably identifies morphological features of coronary instability, such as plaque rupture or erosion. We aimed to prospectively compare these two innovative biotechnologies in the characterization of coronary artery inflammation, which has never been attempted before. Methods OCT and FDG PET/CT were performed in 18 patients with single vessel coronary artery disease, treated by percutaneous coronary intervention (PCI) with stent implantation, divided into 2 groups: NSTEMI/UA (n = 10) and stable angina (n = 8) patients. Results Plaque rupture/erosion recurred more frequently [100% vs 25%, p = 0.001] and FDG uptake was greater [TBR median 1.50 vs 0.87, p = 0.004] in NSTEMI/UA than stable angina patients. FDG uptake resulted greater in patients with than without plaque rupture/erosion [1.2 (0.86–1.96) vs 0.87 (0.66–1.07), p = 0.013]. Among NSTEMI/UA patients, no significant difference in FDG uptake was found between ruptured and eroded plaques. The highest FDG uptake values were found in ruptured plaques, belonging to patients with NSTEMI/UA. OCT and PET/CT agreed in 72% of patients [p = 0.018]: 100% of patients with plaque rupture/erosion and increased FDG uptake had NSTEMI/UA. Conclusion For the first time, we demonstrated that the correspondence between increased FDG uptake with PET/CT and morphology of coronary plaque instability at OCT is high.

The association between thrombosis, cancer and inflammation is well-established. Platelets play a major role in atherosclerosis, inflammation and immune response. Furthermore, growing evidence suggests that they are also significantly involved in tumor development and progression so that anti-platelet agents may prevent cancer and improve outcomes in oncological patients. In this review, we aimed at analyzing the relationship between platelets, cardiovascular diseases and cancer. A comprehensive study in the main educational platforms was performed and high-quality original articles and reviews were included.This review will focus on the role of platelets in cardiovascular disease and in cancer genesis and progression, analyzing their function as immune cells that link inflammation to thrombosis. Finally, it will examine the recent controversies on the use of anti-platelet agents as cancer medications, in particular the already known anti-tumor properties of aspirin, as well as the new perspectives regarding P2Y12 inhibitors.Platelet-cancer crosstalk generates a vicious feed-back loop involving tumor cells and secreting molecules that activate platelets, which in turn promote cancer-associated inflammation, proliferation, spreading and immune system evasion. Therefore, platelets inhibition may represent an innovative therapeutical strategy offered to cancer patients, in the perspective of personalized medicine.

Funding Acknowledgements Type of funding sources: None. Background In patients with hypertrophic cardiomyopathy (HCM) accurate risk stratification for new onset atrial fibrillation (AF) has important prognostic implications. Left atrioventricular coupling index (LACI) has been recently associated with the occurrence of AF in patients without history of cardiovascular disease. Purpose The objective of this study was to investigate the association between LACI and new onset AF in HCM patients and its incremental value over conventional left atrial (LA) parameters. Methods A total of 373 HCM patients without history of AF (48 ± 17 years, 66% men) were evaluated by transthoracic echocardiography. LACI was defined by the ratio of the LA end-diastolic volume divided by the LV end-diastolic volume. The cut-off value for LACI (≥40%) to identify LA-left ventricular (LV) uncoupling was chosen based on the risk excess of new-onset AF described with a spline curve analysis. Cox proportional hazard models were used to evaluate the association between LACI and the occurrence of AF. Results The median LACI was 38% (interquartile range: 24-56) and LA-LV uncoupling (LACI ≥40%) was observed in 171 (45.8%) patients. During a mean follow-up of 11.0 ± 5.6 years, 118 subjects (31.6%) developed new-onset AF. The cumulative event-free survival at 10 years was 53% for patients with LA-LV uncoupling (LACI ≥40%) versus 94% for patients without LA-LV uncoupling (LACI Conclusion Greater LACI, indicative of LA-LV uncoupling, was independently associated with the occurrence of new-onset AF in patients with HCM and demonstrated a stronger risk discrimination power compared to conventional LA parameters. This simple ratio may be easily implemented in clinical practice to improve risk stratification for new-onset AF in HCM. Abstract Figure. Incident AF according to LACI Abstract Figure.

Aims To provide multi-national, multi-ethnic data on the clinical characteristics and prognosis of patients with microvascular angina (MVA). Methods and results The Coronary Vasomotor Disorders International Study Group proposed the diagnostic criteria for MVA. We prospectively evaluated the clinical characteristics of patients according to these criteria and their prognosis. The primary endpoint was the composite of major cardiovascular events (MACE), verified by institutional investigators, which included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. During the period from 1 July 2015 to 31 December 2018, 686 patients with MVA were registered from 14 institutes in 7 countries from 4 continents. Among them, 64% were female and the main ethnic groups were Caucasians (61%) and Asians (29%). During follow-up of a median of 398 days (IQR 365–744), 78 MACE occurred (6.4% in men vs. 8.6% in women, P = 0.19). Multivariable Cox proportional hazard analysis disclosed that hypertension and previous history of coronary artery disease (CAD), including acute coronary syndrome and stable angina pectoris, were independent predictors of MACE. There was no sex or ethnic difference in prognosis, although women had lower Seattle Angina Questionnaire scores than men (P < 0.05). Conclusions This first international study provides novel evidence that MVA is an important health problem regardless of sex or ethnicity that a diagnosis of MVA portends a substantial risk for MACE associated with hypertension and previous history of CAD, and that women have a lower quality of life than men despite the comparable prognosis., Graphical Abstract

2D speckle tracking echocardiography (2DSTE) is superior to standard echocardiography in the assessment of subtle right ventricle (RV) systolic dysfunction. In this study we aimed to: 1) test the hypothesis that 2DSTE may unveil subtle RV systolic dysfunction in patients with Fabry disease; 2) investigate whether the physiologic difference between the 3-segment (RV-FWS) and the 6-segment (RV-GLS) RV strain (∆RV strain) is preserved in Fabry patients.Standard echocardiography and 2DSTE were performed in 49 Fabry patients and 49 age- and sex-matched healthy controls. Fabry patients were divided in two groups according to the presence/absence of left ventricular hypertrophy (LVH+: left ventricular wall thickness 12 mm, 49% of total Fabry patients). RV systolic function assessed by standard echocardiography was normal in the majority of Fabry patients (92%) while RV-GLS and RV-FWS were impaired in about 40%. RV-GLS and RV-FWS were significantly worse in patients LVH+ vs LVH- and vs controls (RV-GLS: LVH+ vs LVH-: -18.4 ± -4.3% vs -23.8 ± -3.1% p0.001; LVH+ vs controls: -18.4 ± -4.3% vs -23.9 ± -2.8% p0.001; RV-FWS: LVH+ vs LVH-: -21.8 ± -5.3% vs -26.7 ± -3.8% p = 0.002, LVH+ vs controls -21.8 ± -5.3% vs -26.8 ± -3.9% p0.001). No difference was found between LVH- patients and controls in both RV-GLS (p = 0.65) and RV-FWS (p = 0.79). ∆RV strain was similar among the groups.In Fabry cardiomyopathy impaired RV-GLS and RV-FWS is a common finding, while RV strain is preserved in Fabry patients without overt cardiac involvement. The physiologic difference between RV-FWS and RV-GLS is maintained in Fabry patients, regardless of the presence of cardiomyopathy.

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor highly expressed in coronary plaques, particularly in macrophages, and in activated platelets. Thus, a possible role in the pathogenesis of acute coronary syndrome (ACS) has been suggested. We evaluated systemic BDNF levels according to the different clinical presentations of ACS. Moreover, we assessed the relationship between BDNF levels and the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) and healed plaques along the culprit vessel. We enrolled consecutive patients presenting with ST-elevation myocardial infarction (STEMI) or non-ST-elevation (NSTE)-ACS. Serum BDNF levels were assessed by enzyme-linked immunosorbent assay. Plaque characteristics of the culprit vessel were assessed by OCT. Among 126 ACS patients (median age 68.00, interquartile range [IQR] 59.75-75.25 years, male 74.6%, 71 (56.3%) were NSTE-ACS and 55 (43.7%) were STEMI. BDNF levels were higher in STEMI patients compared to NSTE-ACS. OCT assessment was performed in 53 (42.1%) patients. Patients with MØI (n = 27) had higher BDNF levels compared to patients without MØI. Furthermore, patients with healed plaques (n = 13) had lower BDNF levels than patients without healed plaques. At multivariate regression analysis BDNF levels independently predicted the presence of MØI (odds ratio [OR] = 2.856; 95% confidence interval [CI] [1.151-7.090], P = 0.024) and the absence of healed plaques (OR = 0.438, 95% CI [0.185-0.992], P= 0.050). Among ACS patients, BDNF levels were higher in patients with STEMI. Moreover, BDNF levels were independently associated with MØI and with the absence of healed plaques along the culprit vessel, suggesting a possible role of BDNF in promoting plaque inflammation, destabilization and occlusive thrombosis.

Although the attention of the world and the global health community specifically is deservedly focused on the COVID-19 pandemic, other determinants of health continue to have large impacts and may also interact with COVID-19. Air pollution is one crucial example. Established evidence from other respiratory viruses and emerging evidence for COVID-19 specifically indicates that air pollution alters respiratory defense mechanisms leading to worsened infection severity. Air pollution also contributes to co-morbidities that are known to worsen outcomes amongst those infected with COVID-19, and air pollution may also enhance infection transmission due to its impact on more frequent coughing. Yet despite the massive disruption of the COVID-19 pandemic, there are reasons for optimism: broad societal lockdowns have shown us a glimpse of what a future with strong air pollution measures could yield. Thus, the urgency to combat air pollution is not diminished, but instead heightened in the context of the pandemic.

Takotsubo syndrome (TS) is an acute and reversible form of myocardial stunning preceded by emotional or physical stress, not explained by an obstruction of an epicardial coronary artery as in acute coronary syndrome. Over the last decades, TS is receiving growing attention, leading to an increase in awareness and diagnostic rate. Chest pain and dyspnea are the most common presenting symptoms; however, nonspecific presentations make the diagnosis challenging for clinicians. Here, we present the case of a 76-year-old female who experienced two completely asymptomatic episodes of TS 20 years apart.

For decades, we have known from autopsy observations that the proximate cause of the majority of acute coronary syndromes ( ACS) is occlusive thrombosis generated by plaque rupture or, less frequently, superficial erosion. Patients with ACS caused by plaque erosion seem to have a better long-term prognosis compared to those with plaque rupture, and may be stabilized by dual antiplatelet therapy without the need for stenting in a non-trivial proportion of cases, limiting the expenses and potential complications of invasive procedures. The accurate prediction of plaque erosion and the identification of specific biomarkers that could be used at the point-of-care without the need of invasive imaging would take us a step closer to the holy grail of precision medicine in patients with ACS.

Acute Coronary Syndromes (ACS) with plaque erosion display dysregulated hyaluronan metabolism, with increased hyaluronidase-2 (HYAL2) expression. However, the expression and the role of this enzyme on platelets has never been explored. We evaluated the platelet’s HYAL2 (pltHYAL2) levels on I) stable angina (SA) and II) ACS patients, furtherly sub-grouped in Intact-Fibrous-Cap (IFC) and Ruptured-Fibrous-Cap (RFC), according to Optical Coherence Tomography. We assessed the HYAL2 role through an in vitro model setting of co-cultured monocytes and platelets, before and after treatment with low-molecular-weight hyaluronic acid (HA) as pro-inflammatory stimulus and with or without HYAL2-antibody to inhibit HYAL2 activity. ACS patients exhibit higher pltHYAL2 levels comparing to SA, with the higher expression for IFC group. The addition of HYAL2-antibody significantly reduced the percentage of monocyte-platelet binding, suggesting that pltHYAL2 enrichment at the site of the culprit lesion is a key mediator in the systemic thrombo-inflammatory status of ACS presenting with plaque erosion., Graphical Abstract Representation of platelet Hyaluronidase 2 involvement in monocyte-platelet aggregates and pathogenesis of plaque erosion. (Ab, antibody; ECM, extracellular matrix; EC, endothelial cells, HYAL2, hyaluronidase 2; LMW-HA, low molecular weight-hyaluronan)

Aims Randomized trials support the safety and efficacy of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation (AF), leading to increased use of these compounds. Crushed forms of DOACs have shown to be reliable, but evidence supporting percutaneous endoscopic gastrostomy (PEG) delivery is lacking. PEG is a long-term option for enteral food and drug delivery in patients unable to maintain oral intake, bypassing the risks and disadvantages of parenteral nutrition. We investigate the safety and efficacy of Edoxaban administered via PEG in patients with atrial fibrillation and a clinical indication for a long-term anticoagulation. Methods and results In this prospective, single centre observational study, 12 PEG-treated patients with indication to anticoagulation will receive edoxaban via PEG and will be followed-up to 6 months. Plasma anti-Factor Xa activity and edoxaban concentrations will be assessed. Thromboembolic (ischaemic stroke, systemic embolism, venous thromboembolism) and bleeding events (Bleeding Academic Research Consortium and Thrombolysis in Myocardial Infarction) will be recorded at 1 and 6 months. A retrospective analysis of 5 AF cases undergoing PEG-implantation at our Institution, who received edoxaban via PEG, showed plasma anti-FXa levels at steady state of 146 ± 15 ng/ml, without major adverse event at a mean follow-up of 6 months. Conclusion We prospectively investigate PEG-administration of edoxaban in PEG-treated patients requiring long term anticoagulation. Our preliminary retrospective data support this route of DOAC administration.

Background Cardiac amyloidosis (CA) is a rapidly progressive infiltrative cardiomyopathy, whose role is emerging as a not-so-rare disorder leading to heart failure (HF). Myocardial bridge (MB) is the most common inborn coronary artery variant, and its clinical relevance is still matter of debate. The exceptional coexistence of these two conditions could accelerate disease progression and worsen the already compromised clinical conditions. Case summary We present the case of a 76-year-old female patient experiencing relapsing HF decompensation and presenting to our centre with dyspnoea at rest and severe peripheral congestion. Echocardiogram showed severe concentric hypertrophy, severe biventricular contractile dysfunction, and third-degree diastolic dysfunction. Coronary angiography excluded epicardial atherosclerotic disease, though displaying a long intramyocardial course of left anterior descending artery. Physiological invasive test was achieved in terms of instantaneous wave-free ratio (iFR), both at baseline and after inotropic and chronotropic stimuli, and attested haemodynamic significance. Concurrently, the diagnostic flow chart for CA was accomplished, by means of both invasive (periumbilical fat biopsy, bone marrow aspiration) and non-invasive tests (99mTc-diphosphonate scintigraphy, serum-urine immunofixation) that confirmed the suspect of primary amyloidosis. Acute HF therapy was personalized according to the singularity of the case, avoiding both nitrates and beta-blockers, then first cycle of chemotherapy was started. Discussion Our clinical case shows a unique interaction between infiltrative cardiomyopathy and coronary artery abnormality. Amyloidosis can contribute to the ischaemic burden of the MB and this may, in turn, abbreviate the path to HF decompensation.

Aims To assess the association between combination, dose and use of current guideline-recommended target doses (TD) of renin-angiotensin system inhibitors (RASi), angiotensin receptor-neprilysin inhibitors (ARNi) and beta-blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure (HF) and reduced ejection fraction. Methods and results Overall, 17 809 outpatients registered in the Swedish Heart Failure Registry (SwedeHF) from May 2000 to December 2018, with ejection fraction = 90 days were selected. Primary outcome was a composite of time to cardiovascular death and first HF hospitalization. Compared with no use of RASi or ARNi, the adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.83 (0.76-0.91) with = 100% of TD. Compared with no use of beta-blockers, the adjusted HR (95% CI) was 0.86 (0.76-0.91), 0.81 (0.74-0.89) and 0.74 (0.68-0.82) with = 100% of TD, respectively. Patients receiving both an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/ARNi and a beta-blocker at 50%-99% of TD had a lower adjusted risk of the primary outcome compared with patients only receiving one drug, i.e. ACEi/ARB/ARNi or beta-blocker, even if this was at >= 100% of TD. Conclusion Heart failure with reduced ejection fraction patients using higher doses of RASi or ARNi and beta-blockers had lower risk of cardiovascular death or HF hospitalization. Use of two drug classes at 50%-99% of TD dose was associated with lower risk than one drug class at 100% of TD. Funding Agencies|EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking BigData@Heart grant [116074]