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Congestion is a cardinal sign of heart failure (HF). In the past, it was seen as a homogeneous epiphenomenon that identified patients with advanced HF. However, current evidence shows that congestion in HF varies in quantity and distribution. This updated view advocates for a congestive-driven classification of HF according to onset (acute vs. chronic), regional distribution (systemic vs. pulmonary), compartment of distribution (intravascular vs. extravascular), and clinical vs. subclinical. Thus, this review will focus on the utility of circulating biomarkers for assessing and managing the different fluid overload phenotypes. This discussion focused on the clinical utility of the natriuretic peptides, carbohydrate antigen 125 (also called mucin 16), bio-adrenomedullin and mid-regional pro-adrenomedullin, ST2 (also known as interleukin-1 receptor-like 1), cluster of differentiation 146, troponin, C-terminal pro-endothelin-1, and parameters of haemoconcentration. The utility of circulation biomarkers on top of clinical evaluation, haemodynamics, and imaging needs to be better determined by dedicated studies. Some multiparametric frameworks in which these tools contribute to management are proposed.

Knowledge on risk predictors of incident heart failure (HF) in patients with type 2 diabetes (T2D) is crucial given the frequent coexistence of the two conditions and the fact that T2D doubles the risk of incident HF. In addition, HF is increasingly being recognized as an important endpoint in trials in T2D. On the other hand, the diagnostic and prognostic performance of established cardiovascular biomarkers may be modified by the presence of T2D. The present position paper, derived by an expert panel workshop organized by the Heart Failure Association of the European Society of Cardiology, summarizes the current knowledge and gaps in evidence regarding the use of a series of different biomarkers, reflecting various pathogenic pathways, for the prediction of incident HF and cardiovascular events in patients with T2D and in those with established HF and T2D.

In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with heart failure with reduced ejection fraction because most studies on cardiac remodelling focused on this setting. © 2022 European Society of Cardiology.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally used for diabetes mellitus, are gaining more popularity for other indications owing to their positive cardiovascular and renal effects. Initially, SGLT2 inhibitors were shown to reduce heart failure (HF) hospitalization and improve cardiovascular outcomes in patients with type 2 diabetes. Later, SGLT2 inhibitors were evaluated in patients with HF with reduced ejection fraction (HFREF) and had beneficial effects independent of the presence of diabetes. Recently, reduction in cardiovascular outcomes were also observed in patients with HF with preserved ejection fraction (HFPEF). SGLT2 inhibitors also reduced renal outcomes in patients with chronic kidney disease. Overall, these drugs have an excellent safety profile with a negligible risk of genitourinary tract infections and ketoacidosis. In this review, we discuss the current data regarding SGLT2 inhibitors in special populations including acute myocardial infarction, acute HF, right ventricular (RV) failure, patients with left ventricular assist device (LVAD), and patients with type1 diabetes. We also discuss the potential mechanisms behind the cardiovascular benefits of these drugs.

This clinical consensus statement reviews the use of inotropic support in patients with advanced heart failure. The current guidelines only support use of inotropes in the setting of acute decompensated heart failure with evidence of organ malperfusion or shock. However, inotropic support may be reasonable in other patients with advanced heart failure without acute severe decompensation. The clinical evidence supporting use of inotropes in these situations is reviewed. Particularly, patients with persistent congestion, systemic hypoperfusion, or advanced heart failure with need for palliation, and specific situations relevant to implantation of left ventricular assist devices or heart transplantation are discussed. Traditional and novel drugs with inotropic effects are discussed and use of guideline-directed therapy during inotropic support is reviewed. Finally, home inotropic therapy is described, and palliative care and end-of-life aspects are reviewed in relation to management of ongoing inotropic support (including guidance for maintenance and weaning of chronic inotropic therapy support).

Aims Physical activity (PA) is important in patients with heart failure (HF) to improve health outcomes. The adherence to PA is low, and therefore, novel approaches are necessary to increase PA. We aimed to determine the difference in PA in patients with HF who have access to exergaming compared to patients who received motivational support and to explored predictors of a clinically relevant change in non-sedentary time between baseline and 3 months. Methods and results In total, 64 patients (mean age 69 ± 9 years, 27% female) wore an accelerometer 1 week before and 1 week after the intervention. Data were analysed using logistic regression analysis. Patients spent 9 h and 43 min (±1 h 23 min) during waking hours sedentary. There were no significant differences in PA between patients who received an exergame intervention or motivational support. In total, 30 of 64 patients achieved a clinically relevant increase in non-sedentary time. Having grandchildren [odds ratio (OR) 7.43 P = 0.03], recent diagnosis of HF (OR 0.93 P = 0.02), and higher social motivation (OR 2.31 P = 0.03) were independent predictors of a clinically relevant increase of non-sedentary time. Conclusion Clinicians should encourage their patients to engage in alternative approaches to improve PA and reduce sedentary habits. Future exergaming interventions should target individuals with chronic HF who have low social motivation and a low level of light PA that may benefit most from exergaming. Also (non-familial), intergenerational interaction is important to enabling patients in supporting patients in becoming more active.

To assess the 6 months immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in a population of heart transplanted (HTx) recipients and left ventricular assist device (LVAD)-supported patients.A prospective single-centre cohort study of HTx recipients and LVAD-supported patients who received a two-dose SARSCoV-2 mRNA vaccine (BNT162b2, Pfizer-BioNTech). Whole blood for anti-spike IgG (S-IgG) antibodies were drawn at 6 months after the first vaccine dose. S-IgG data at 6 weeks were available for a subgroup of HTx recipients. S-IgG ≥ 50 AU/mL were interpreted positive. The cohort included 53 HTx recipients and 18 LVAD-supported patients. The median time from HTx or LVAD implantation to the 1At 6 months post-vaccination, S-IgG immunogenicity in HTx recipients is low, particularly in older HTx recipients and in those treated with anti-metabolites drugs.

Aims Exercise games (exergames) have been recently proposed as a mode of facilitating physical activity in patients with chronic diseases. Although patients supported with left ventricular assist devices (LVADs) benefit from physical activity, specific LVAD-related issues hinder their ability to exercise properly. The objective of this study was to assess the feasibility and safety of exergaming in LVAD-supported patients. Methods and results Eleven LVAD-supported patients were enrolled in a 4 week exergaming programme using Nintendo Wii console with five sport games. Patients were instructed to play for 30 min a day, 5 days a week. Data on exercise capacity and exergaming were collected by using the 6 min walk test (6MWT) and a daily self-report diary, respectively. Feasibility of using the console and its safety was assessed by a semi-structured patient interview. Quality of life was assessed by the Minnesota Living with Heart failure Questionnaire (MLHFQ) and the Cantrils Ladder of Life. Safety was assessed by patients report in interview and diary. The study group consisted of 10 male patients and 1 female patient, mean age of 67 +/- 7 years, of whom 10 were supported with the HeartMate 3 LVAD for a median of 10 (interquartile range 3, 21) months. Baseline exercise capacity assessed by the 6MWT ranged from 240 to 570 m (mean 448 +/- 112). After 4 weeks of exergaming, 6MWT distance increased from a mean of 448 +/- 112 (evaluated in six patients) to 472 +/- 113 m (P = 0.023). Patients Cantrils Ladder of Life score improved numerically from an average of 6.13 to 7.67, as did their MLHFQ score from 45.9 +/- 27 to 38.7 +/- 18, with higher and lower scores, respectively, reflecting higher quality of life. No specific LVAD-related safety issues regarding exergaming were reported. Conclusions Exergaming was found to be a safe and feasible mode for encouraging physical activity in LVAD-supported patients and carries a potential for improving exercise capacity and quality of life in these patients. Larger scale studies are warranted to further investigate the effect of exergaming in this patient population. Funding Agencies|Swedish National Science Council [2016-01390]

Aims This study aimed to explore factors related to non-adherence to exergaming in patients with heart failure. Methods and results Data from patients in the exergame group in the HF-Wii trial were used. Adherence to exergaming was defined as playing 80% or more of the recommended time. Data on adherence and reasons for not exergaming at all were collected during phone calls after 2, 4, 8, and 12 weeks. Logistic regression was performed between patients who were adherent and patients who were non-adherent. Secondly, a logistic regression was performed between patients who not exergamed at all and patients who were adherent to exergaming. Finally, we analysed the reasons for not exergaming at all with manifest content analysis. Almost half of the patients were adherent to exergaming. Patients who were adherent had lower social motivation [odds ratio (OR) 0.072; 95% confidence interval (CI) 0.054-0.095], fewer sleeping problems (OR 0.84; 95% CI 0.76-0.092), and higher exercise capacity (OR 1.003; 95% CI 1.001-1.005) compared with patients who were non-adherent. Patients who not exergamed at all had lower cognition (OR 1.18; 95% CI 1.06-1.31) and more often suffered from peripheral vascular disease (OR 3.74; 95% CI 1.01-13.83) compared with patients who were adherent to exergaming. Patients most often cited disease-specific barriers as a reason for not exergaming at all. Conclusions A thorough baseline assessment of physical function and cognition is needed before beginning an exergame intervention. It is important to offer the possibility to exergame with others, to be able to adapt the intensity of physical activity. Funding Agencies|Swedish National Science Council [K2013-69X-22302-01-3, 2016-01390]; Swedish National Science Council/the Swedish Research Council for Health, Working Life and Welfare, VR-FORTE [2014-4100]; Swedish Heart and Lung Association [Hjart-Lungfonden] [E085/12]; Swedish Heart and Lung Foundation (Hjart-Lungfonden) [20130340, 20160439]; Vardal Foundation (Vardalstiftelsen) [2014-0018]; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [FORSS 474681]

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large phenotypic variability in CS, as a result of the diverse aetiologies, pathogenetic mechanisms, haemodynamics, and stages of severity. Although early revascularization remains the most important intervention for CS in settings of acute myocardial infarction, the administration of timely and effective antithrombotic therapy is critical to improving outcomes in these patients. In addition, other clinical settings or non‐acute myocardial infarction aetiologies, associated with high thrombotic risk, may require specific regimens of short‐term or long‐term antithrombotic therapy. In CS, altered tissue perfusion, inflammation, and multi‐organ dysfunction induce unpredictable alterations to antithrombotic drugs' pharmacokinetics and pharmacodynamics. Other interventions used in the management of CS, such as mechanical circulatory support, renal replacement therapies, or targeted temperature management, influence both thrombotic and bleeding risks and may require specific antithrombotic strategies. In order to optimize safety and efficacy of these therapies in CS, antithrombotic management should be more adapted to CS clinical scenario or specific device, with individualized antithrombotic regimens in terms of type of treatment, dose, and duration. In addition, patients with CS require a close and appropriate monitoring of antithrombotic therapies to safely balance the increased risk of bleeding and thrombosis.

Endothelial microvascular dysfunction is a known mechanism of vascular pathology in cardiac amyloidosis (CA). Scientific evidence regarding the possible protective role of the amyloid transthyretin (ATTR) stabilizer, tafamidis, is lacking. Circulating endothelial progenitor cells (cEPCs) have an important role in the process of vascular repair. We aimed to examine the effect of tafamidis on cEPCs. Study population included patients with ATTR-CA. cEPCs were assessed using flow cytometry by the expression of CD34(+)/CD133(+) and vascular endothelial growth factor receptor (VEGFR)-2(+) and by the formation of colony-forming units (CFUs) and production of VEGF. Tests were repeated at pre-specified time-points up to 12 months following the initiation of tafamidis. Included were 18 ATTR-CA patients at a median age of 77 (IQR 71, 85) years and male predominance (n = 15, 83%). Following the initiation of tafamidis and during 12 months of drug treatment, there was a gradual increase in the levels of CD34(+)/VEGFR-2(+) (0.43 to 2.42% (IQR 1.53, 2.91)%, p = 0.002) and CD133(+)/VEGFR-2(+) (0.49 to 1.64% (IQR 0.97, 2.90)%, p = 0.004). Functionally, increase in EPCs-CFUs was microscopically evident following treatment with tafamidis (from 0.5 CFUs (IQR 0.0, 1.0) to 3.0 (IQR 1.3, 3.8) p

Heart failure (HF) is linked to to high mortality rates and recurrent hospitalisations despite medical and device-based achievements. The use of left ventricular assist devices (LVADs) has improved survival among patients with advanced HF. Significant progress has been achieved with the new generation of continuous-flow devices, particularly with the fully magnetically levitated HeartMate 3. In June 2021, Medtronic announced the abrupt withdrawal of the HeartWare device from the market. This decision has introduced a new era in which the field of mechanical support for advanced HF patients is dominated by a single device – the HeartMate 3. The direct clinical and economic consequences of this change will necessitate new surgical considerations. Because of the expected need for HeartWare device replacement in small patients, new surgical techniques and device adaptation will be needed. The new single-device era will hopefully encourage scientists and engineers to create innovations in the advanced HF arena. Special considerations should be taken during the COVID-19 pandemic when treating patients with LVADs.

We aimed to describe the natural history of left ventricular assist device (LVAD)-supported patients with preimplantation significant tricuspid regurgitation (TR) in a single-center retrospective analysis of LVAD-implanted patients (2008-2019). TR severity was assessed semiqualitatively using color-Doppler flow: insignificant TR (iTR) was defined as none/mild TR and significant TR (sTR) as ≥moderate TR. Included were 121 LVAD-supported patients of which 53% (n = 64) demonstrated sTR preimplantation. Among patients with pre-LVAD implantation sTR and available echocardiographic data, 55% (n = 26) ameliorated their TR severity grade to iTR during the first-year postsurgery and 55% (n = 17) had iTR at 2-year follow-up. On univariate analysis, predictors for TR severity improvement post-LVAD implantation were preimplant lack of atrial fibrillation, reduced inferior vena cavae diameter, and elevated pulmonary vascular resistance. In patients who failed to improve their TR severity grade, we observed a deterioration in right ventricular (RV) function (pulmonary artery pressure index 2.0 [1.7, 2.9], a decline in RV work index 242 [150, 471] mm Hg·L/m2) and higher loop-diuretics dose requirement. At a median of 21 (IQR 8, 40) months follow-up, clinical LVAD-related complications, heart failure-hospitalizations, and overall survival were similar among patients who improved versus failed to improve their TR severity-grade post-LVAD implantation. In conclusion, LVAD implantation is accompanied by a reduction in TR severity in approximately 50% of patients. In patients who failed to improve their TR severity grade, progressive RV dysfunction was observed. Overall, an isolated LVAD implantation in patients with sTR does not adversely affect survival.

AimsNon-invasive coronary assessment using single-photon emission computerized tomography (SPECT) testing for potential cardiac ischemia is an essential part of the evaluation of kidney transplant candidates. We aimed to examine the prognostic value of preoperative SPECT test results in kidney transplanted patients.Methods and resultsWe retrospectively analyzed the pre-surgical nuclear SPECT test results in a registry of kidney transplanted patients. Follow-up at 1 month and 1 year recorded major adverse cardiac events (MACE) including non-fatal myocardial infarction, all-cause mortality and hospitalization due to cardiovascular disease following the renal transplantation. Of 577 patients available for analysis, 408 (70.9%) patients underwent nuclear SPECT test pre-transplant and 83 (20.3%) had abnormal results with either evidence of ischemia or infarct. A significantly higher incidence of post-operative MACE at 1 month was evident among patients with abnormal SPECT test compared to patients with no evidence of ischemia (10.8 vs. 4.3% respectively; P = 0.019). Differences were mostly derived from significantly increased rates of myocardial infarction events (8.4 vs. 1.8%; P = 0.002). Yet, MACE rate was not statistically different at 1 year (20.5 vs. 13.1%; P = 0.88). Importantly, the prognostic impact of an abnormal SPECT was significantly attenuated for all outcomes following multivariable adjusting for conventional cardiovascular risk factors and coronary revascularization.ConclusionPre-surgical cardiac risk assessment of kidney transplant candidates with nuclear SPECT test was found to be predictive of post-operative MACE, yet apparently, its prognostic value was significantly attenuated when adjusted for cardiac risk factors.

The coronavirus 2019 (COVID-19) infection pandemic has affected the care of patients with heart failure (HF). Several consensus documents describe the appropriate diagnostic algorithm and treatment approach for patients with HF and associated COVID-19 infection. However, few questions about the mechanisms by which COVID can exacerbate HF in patients with high-risk (Stage B) or symptomatic HF (Stage C) remain unanswered. Therefore, the type of HF occurring during infection is poorly investigated. The diagnostic differentiation and management should be focused on the identification of the HF phenotype, underlying causes, and subsequent tailored therapy. In this framework, the relationship existing between COVID and onset of acute decompensated HF, isolated right HF, and cardiogenic shock is questioned, and the specific management is mainly based on local hospital organization rather than a standardized model. Similarly, some specific populations such as advanced HF, heart transplant, patients with left ventricular assist device (LVAD), or valve disease remain under investigated. In this systematic review, we examine recent advances regarding the relationships between HF and COVID-19 pandemic with respect to epidemiology, pathogenetic mechanisms, and differential diagnosis. Also, according to the recent HF guidelines definition, we highlight different clinical profile identification, pointing out the main concerns in understudied HF populations.

Heart failure (HF) is a long-term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC-HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs—in terms of quality of life—in European countries.

AIMS: To assess the short-term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in a population of heart transplant (HTx) recipients. A prospective single-centre cohort study of HTx recipients who received a two-dose SARS-CoV-2 mRNA vaccine (BNT162b2, Pfizer-BioNTech). METHODS AND RESULTS: Whole blood for anti-spike IgG (S-IgG) antibodies was drawn at days 21-26 and at days 35-40 after the first vaccine dose. Geometric mean titres (GMT) ≥50 AU/mL were interpreted positive. Included were 42 HTx recipients at a median age of 61 [interquartile range (IQR) 44-69] years. Median time from HTx to the first vaccine dose was 9.1 (IQR 2.6-14) years. Only 15% of HTx recipients demonstrated the presence of positive S-IgG antibody titres in response to the first vaccine dose [GMT 90 (IQR 54-229) AU/mL]. Overall, 49% of HTx recipients induced S-IgG antibodies in response to either the first or the full two-dose vaccine schedule [GMT 426 (IQR 106-884) AU/mL]. Older age [68 (IQR 59-70) years vs. 46 (IQR 34-63) years, P = 0.034] and anti-metabolite-based immunosuppression protocols (89% vs. 44%, P = 0.011) were associated with low immunogenicity. Importantly, 36% of HTx recipients who were non-responders to the first vaccine dose became S-IgG seropositive in response to the second vaccine dose. Approximately a half of HTx recipients did not generate S-IgG antibodies following SARS-CoV-2 two-dose vaccine. CONCLUSIONS: The generally achieved protection from SARS-CoV-2 mRNA vaccination should be regarded with caution in the population of HTx recipients. The possible benefit of additive vaccine should be further studied.

Aims This study aimed to evaluate the different health‐related quality of life (HR‐QoL) aspects in patients with both short‐term and long‐term duration LVAD support at pre‐specified time intervals. Methods and results We performed a single‐centre HR‐QoL analysis of short‐term and long‐term LVAD‐supported patients using the short version of the Kansas City Cardiomyopathy Questionnaire (KCCQ‐12) and the Changes in Sexual Functioning Questionnaire along with a survey to evaluate patients' social and driving routines. Data were collected at baseline and at 6 or 12 month follow‐up. Included were 46 patients with a median time from LVAD implantation of 1.1 [inter‐quartile range (IQR) 0.5, 2.6] years. The median KCCQ‐12 summary score was 56 (IQR 29, 74) with most favourable scores in the symptom frequency domain [75 (IQR 50, 92)] and worse scores in the physical limitation [42 (IQR 25, 75)] and QoL [44 (IQR 25, 75)] domains. No significant changes were apparent during study follow‐up [KCCQ‐12 summary score 56 (IQR 35, 80)], and no significant correlation between the KCCQ‐12 summary score and ventricular assist device‐support duration was detected (r = −0.036, P = 0.812). Sexual dysfunction was noted across all domains with a cumulative score of 31 (IQR 22, 42). Seventy‐six per cent of patients resumed driving after LVAD implantation, and 43% of patients reported they socialize with family and friends more frequently since surgery. Conclusions Short‐term and long‐term LVAD‐supported patients had impaired HR‐QoL and sexual function at baseline and at follow‐up yet reported an improvement in social interactions and independency. A broader spectrum of patient's reported HR‐QoL measures should be integrated into the pre‐LVAD implantation assessment and preparation.

Background AKI is a known complication of PCI and is associated with higher rates of adverse events. We assessed temporal trends in rates of AKI, factors associated with risk of AKI and prognosis. Methods From a prospective registry of patients undergoing PCI at two hospitals of the Rabin Medical Center, 15,153 consecutive patients were assessed at two time periods: 2006–2012 and 2012–2018. AKI was defined as either a relative elevation of ≥25% in serum creatinine or an absolute elevation of ≥0.5 mg/dl in serum creatinine at 48 h post PCI. Results Data for 7913 patients from 2006 to 2012 and 7240 during 2012–2018 was available for analysis. Mean age was 65.0 ± 11.9y and 66.0 ± 12.3y (p Conclusions Over time, there was an improvement in the rates of post-PCI AKI. Increased adverse outcomes were evident at both periods. Further research is warranted, to further reduce peri-procedural AKI which is associated with impaired prognosis.

Introduction There is limited data on the long-term follow-up of patients with myocarditis. Aim To investigate the long-term follow-up of patients with myocarditis. Material and methods We performed a retrospective observational analysis on the clinical long-term outcomes of patients with myocarditis over a 10-year period. The primary outcome was mortality. We identified risk factors for mortality and adverse clinical outcomes. We also compared the characteristics and outcomes of patients presenting with fulminant myocarditis to those presenting with non-fulminant myocarditis. Results Between May 2004 and December 2014, 203 patients with myocarditis or perimyocarditis were admitted to our center. Most patients were male (87.7%) with a median age at presentation of 33 years (interquartile range: 25.4-38.9). The median follow-up period was 56.9 months (interquartile range 25.3-87.3 months), during which the overall mortality was 4.4% (9 patients). Fifteen patients presented with fulminant myocarditis. After multivariable analysis, older age (HR = 1.11, 95% CI: 1.05-1.16, p < 0.001) and a poorer New York Heart Association (NYHA) function class (HR = 4.6, 95% CI: 1.18-18, p = 0.028) were found to be independently associated with a higher risk of mortality, whereas higher albumin levels at presentation (HR = 0.2, 95% CI: 0.07-0.56, p = 0.002) were associated with decreased mortality. The group presenting with fulminant myocarditis had a more severe course of disease and a higher in-hospital mortality (13.3% vs. 0%, p = 0.005). Conclusions The overall prognosis of patients with myocarditis is good - in terms of both survival and recovery without residual left ventricular dysfunction.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally used for diabetes mellitus, are gaining more popularity for other indications, owing to their positive cardiovascular and renal effects. SGLT2 inhibitors reduce heart failure (HF) hospitalization and improve cardiovascular outcomes in patients with type 2 diabetes. Later, SGLT2 inhibitors were evaluated in patients with HF with reduced ejection fraction (HFREF) and had beneficial effects independent of the presence of diabetes. Recently, reductions in cardiovascular outcomes were also observed in patients with HF with preserved ejection fraction (HFPEF). SGLT2 inhibitors also reduced renal outcomes in patients with chronic kidney disease. Overall, these drugs have an excellent safety profile with a negligible risk of genitourinary tract infections and ketoacidosis. In this review, we discuss the current data on SGLT2 inhibitors in special populations, including patients with acute myocardial infarction, acute HF, right ventricular (RV) failure, left ventricular assist device (LVAD), and type 1 diabetes. We also discuss the potential mechanisms behind the cardiovascular benefits of these medications.

A left ventricular assist device (LVAD) is a mechanical device that treats advanced heart failure. Patients coping with an LVAD need extensive instrumental and medical support, which is usually provided by the spouse. Therefore, it seems that dyadic coping strategies play a crucial role as either mitigators or hinderers of couples’ illness management in the context of LVADs. The aim of this research was to formulate a typology of dyadic coping strategies applied by these couples, as unfolded in their mutual and individual subjective experiences. The research was performed in collaboration with an LVAD implantation unit at a medium-sized hospital in Israel. Couples ( N = 17) participated in an in-depth dyadic interview using a semi-structured interview guide, and the data collected were analyzed using content analysis. Our findings suggest that couples coping with an LVAD develop strategies for handling fear, processing and accepting their illness narratives, adjusting their level of independence and intimacy, and utilizing humor. Moreover, our analysis showed that each couple utilized a unique mix of dyadic coping strategies. To the best of our knowledge, the current study is the first to explore the dyadic coping strategies of couples coping with an LVAD. Our results may constitute a base for developing dyadic intervention programs and clinical recommendations to improve the quality of life and relationships of patients and their spouses while coping with LVAD implementation.

Background: Among Left Ventricular Assist Device (LVAD) implanted patients, body image modifications might occur. Objectives: To explore the associations between sexual functioning, confidence in LVAD technology, personal wellbeing, and body image. Methods: The cross-sectional study included 30 conveniently recruited LVAD implanted patients who completed Body Image Scale, sexual functioning, confidence in LVAD technology, and Personal Wellbeing Index questionnaires. The associations between the research variables were examined with multiple regression analyses. Results: The mean age of the participants was 63 (SD=10), 90% were men. The mean scores were: sexual functioning 2.43 (SD=1.20, range 1-5); confidence in LVAD technology 2.63 (SD=1.04, range 1-5); Well-Being Index 6.61 (SD=1.53, range 0-10); and body image 14.5 (SD=4.17, range 5-20). Sexual functioning (p

Background Filamin C is a cytoskeletal protein expressed in cardiac cells. Nonsense variations in the filamin C gene (FLNC) were associated with dilated and arrhythmogenic cardiomyopathies. Methods and results We identified an intronic variation in FLNC gene (c.3791-1G > C) in three unrelated Ashkenazi Jewish families with variable expression of arrhythmia and cardiomyopathy. cDNA was prepared from a mutation carrier's cultured skin fibroblasts. Quantitative PCR demonstrated a reduction in total FLNC transcript, and no other FLNC splice variants were found. Single-nucleotide polymorphism (SNP) analysis revealed heterozygous variations in the genomic DNA that were not expressed in the messenger RNA. Immunohistochemical analysis of cardiac sections detected a normal distribution of filamin C protein in the heart ventricles. Conclusion The transcript that included the FLNC variant was degraded. Haploinsufficiency in filamin C underlies arrhythmogenic cardiomyopathy with variable symptoms.

Heart failure (HF) is common and associated with a poor prognosis, despite advances in treatment. Over the last decade cardiovascular outcome trials with sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus have demonstrated beneficial effects for three SGLT2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) in reducing hospitalisations for HF. More recently, dapagliflozin reduced the risk of worsening HF or death from cardiovascular causes in patients with chronic HF with reduced left ventricular ejection fraction, with or without type 2 diabetes mellitus. A number of additional trials in HF patients with reduced and/or preserved left ventricular ejection fraction are ongoing and/or about to be reported. The present position paper summarises recent clinical trial evidence and discusses the role of SGLT2 inhibitors in the treatment of HF, pending the results of ongoing trials in different populations of patients with HF.

BACKGROUND: The assessment of self-care behaviour is important for tailoring care to patients and evaluating the effectiveness of heart failure (HF) disease-management programmes. The European HF Self-care Behaviour (EHFScB) scale is a validated instrument used worldwide. AIM: The purpose of the study was to evaluate psychometric properties of the Hebrew version of the nine-item EHFScB scale in Israeli patients with HF. METHOD: To develop the Hebrew version of the EHFScB scale, forward and back translation was performed. The psychometric evaluation was based on data from 102 patients with HF (mean age 61±12 yr, male 75%, New York Heart Association [NYHA] class II 42% and NYHA class III 51%) included in two cross-sectional studies performed in 2007 and 2015-2017 in an Israeli hospital. Content validity, construct validity, known-groups validity, and discriminant validity were assessed. Reliability was evaluated with internal consistency. RESULTS: Content validity and useability were confirmed by HF experts and patients with HF. Construct validity was tested using factor analysis and two factors were extracted (factor 1: consulting behaviour; factor 2: adherence to the regimen). Known-groups validity testing revealed a significant difference before and after an educational intervention in the total score (n=40 [41.6±23.8] vs [67.6±21.8]; pFunding agencies: Swedish National Science Council [K2013-69X-22302-01-3, 2016-01390]; Swedish National Science Council/Swedish research council for health, working life and welfare (VR-FORTE) [2014-4100]; Swedish Heart and Lung AssociationSwedish Heart-Lung Foundation [E0

To identify predictors and evaluate outcomes of posttransplant diabetes mellitus (PTDM) and to investigate the effect of treatment modalities on outcomes. The database of a tertiary medical center was searched for all adult patients without prior diabetes who underwent lung, liver, or heart transplantation between January 1, 2012 and June 30, 2018. Patients in whom PTDM (defined as HbA1C ≥ 6.5% at least 3 months post transplantation) developed during follow-up (mean 3.32 years) were identified. Risk factors for PTDM, determined by regression analysis and clinical outcomes [all-cause mortality, severe infections, graft loss, and major adverse cardiovascular events (MACE)], were compared between those who developed PTDM and those who did not; in the former, insulin-based therapy was compared with non-insulin regimen. The cohort included 281 transplant recipients: 158 lung, 109 liver, and 14 heart. PTDM was diagnosed in 60 (21.35%) patients at a mean of 11.3 ± 12.89 months post transplantation. The only significant independent risk factor for PTDM was age (HR 1.028, 95% CI = 1.002–1.054, P = 0.0314). PTDM was associated with higher rates of severe infections (HR 2.565, 95% CI = 1.626–4.050, P

Background Left ventricular assist devices (LVADs) support the diseased heart of patients with advanced heart failure and are used as a bridge to heart transplantation or as destination therapy for patients ineligible for heart transplantation. Body image changes, as well as anxiety and depression, are prevalent among patients with an implanted LVAD. Objective The aim of this study was to investigate whether a relationship exists between body image and personal well-being among patients with an implanted LVAD and, if it does, whether it is moderated by anxiety and depression. Methods In this cross-sectional correlational study, a convenience sample of 30 adult patients with an implanted LVAD (mean age, 63 +/- 10; 90% male) from the outpatient facility of a tertiary medical center completed validated instruments including the Body Image Scale, Cosmetic Scale, Hospital Anxiety and Depression Scale, and Personal Well-being Index, from October 2017 to February 2018. Results were subjected to multivariate linear regression and bootstrap moderation analyses. Results Eleven patients (37%) had below-average personal well-being scores, and 14 patients (47%) had below-average body image scores. Seven (23%) had either anxiety or depression, and 11 (37%) had both anxiety and depression. Body image was found to be a significant predictor of personal well-being (t = 2.16, P = .04). When anxiety and depression were present, body image (t = 2.08, P = .049), depression (t = 2.53, P = .018), and the interaction between body image and depression (t = -2.1, P = .047) were significantly associated with personal well-being. Conclusions Body image significantly predicted personal well-being among patients with an implanted LVAD. Depression alone, or depression combined with anxiety, moderated the relationships between body image and personal well-being. The current results may help to heighten healthcare providers awareness of body image perception among patients with an implanted LVAD.

International audience; Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.

Sudden death is a devastating complication of heart failure (HF). Current guidelines recommend an implantable cardioverter-defibrillator (ICD) for prevention of sudden death in patients with HF and reduced ejection fraction (HFrEF) specifically those with a left ventricular ejection fraction

[Abstract] The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of the LVAD-supported patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD-supported patients. The expected and non-expected device-related and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of the LVAD implanting centres. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to experience comorbidities common in the older population. The probability of an LVAD-supported patient presenting with medical emergency to a local emergency department, internal, or surgical ward of a non-LVAD implanting centre is increasing. The purpose of this trilogy is to supply the immediate tools needed by the non-LVAD specialized physician: ambulance clinicians, emergency ward physicians, general cardiologists, internists, anaesthesiologists, and surgeons, to comply with the medical needs of this fast-growing population of LVAD-supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department and from the emergency department to the internal or surgical wards and eventually to the discharge home from the hospital back to the general practitioner. In this first part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, after the introduction on the assist devices technology in general, definitions and structured approach to the assessment of the LVAD-supported patient in the ambulance and emergency department is presented including cardiopulmonary resuscitation for LVAD-supported patients.

Background Adequate self-care behaviour is essential for patients with a left ventricular assist device (LVAD) to prevent complications, prolong life, and optimise quality of life. However, there were no valid and reliable measurements available to assess self-care behaviour among patients with LVAD. We have previously developed the 33-item LVAD self-care behaviour scale. Objectives To evaluate psychometric properties of the 33-item LVAD self-care behaviour scale. Methods and results Data on 127 patients with a LVAD in Israel, Japan, and the USA were analysed (mean age 51±14.3, 81% male). Exploratory factor analysis extracted three factors, and 13 items were excluded from the scale. Internal consistency assessed by Cronbach’s alpha was acceptable for the total scale (α = 0.80) and the three subscales: Factor 1: Monitoring (α = 0.81), Factor 2: Heart failure self-care (α = 0.67), and Factor 3: LVAD self-care (α = 0.63). The 20-item version of the LVAD self-care behaviour scale had sufficient convergent validity with another scale that assessed self-care related to the driveline of LVAD (r = 0.47, p Conclusions The 20-item version of the LVAD self-care behaviour scale showed adequate validity and reliability. The scale is ready for use in clinical practice and research. Additional testing might further optimise the scale.

Takotsubo syndrome is an acute heart failure syndrome with a pathogenesis that is attributed to sympathetic stimulation. This case report describes a unique case of a 5 month heart‐transplanted female patient who developed apical ballooning on an echocardiography exam performed following an emotional stress event. Detailed clinical investigations and imaging techniques confirmed the diagnosis of Takatsubo syndrome. Our case indicates that Takatsubo's cardiomyopathy should be included in the differential diagnosis of heart‐transplanted patients presenting with sudden graft dysfunction mimicking acute graft rejection or acute coronary syndrome.

Aims Cognitive impairment (CI) in heart failure (HF) patients has mostly been studied in single countries in specific health care settings. Sociodemographic and clinical predictors of the global CI and CI dimensions are still unclear. We described CI in a diverse HF population recruited in several countries and in different health care settings and investigated sociodemographic and clinical factors associated with the global and specific CI dimensions in HF patients. Methods and results A secondary analysis from the baseline data of the Wii-HF trial. Patients (n = 605) were enrolled in Sweden, Italy, Israel, The Netherlands, Germany, and the United States. We used the Montreal Cognitive Assessment to evaluate CI and the 6 minute walk test (6MWT) to measure exercise capacity. Patients were on average 67 years old (SD, 12), and 86% were in New York Heart Association Class II and III. The mean Montreal Cognitive Assessment score was 24 (SD, 4), and 67% of patients had at least a mild CI. The item evaluating short-term memory had a considerable proportion of low scoring patients (28.1%). Worse CI was associated with patients older age, lower education, and lower 6MWT scores (R-2 = 0.27). CI dimension scores were differently associated with specific clinical and demographic variables, but the 6MWT scores were associated with five out of seven CI dimension scores. Conclusions CI is an important problem in HF patients, with specific challenges in regard to memory. Exercise capacity is a modifiable factor that could be improved in HF patients with the potential to improve cognition and other outcomes in this population. Funding Agencies|Swedish National Science Council [K2013-69X-22302-01-3, 2016-01390]; Swedish National Science Council/Swedish Research Council for Health, Working Life and Welfare (VR-FORTE) [2014-4100]; Swedish Heart and Lung AssociationSwedish Heart-Lung Foundation [E085/12]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20130340, 20160439]; Vardal Foundation [2014-0018]; Medical Research Council of Southeast Sweden [FORSS 474681]

OBJECTIVES The immunogenicity of two-dose severe acute respiratory syndrome coronavirus 2 vaccine is lower among heart transplant (HTx) recipients, compared with the general population. Our aim was to assess the immunogenicity of a third-dose vaccine in HTx recipients. METHODS This is a prospective cohort study of HTx recipients who received a third dose of the BNT162b2 vaccine. Immunogenicity was assessed by serum levels of anti-spike immunoglobulin G (S-IgG), taken at baseline and 14–28 days after the third dose. Titres above 50 U/ml were interpreted positive. RESULTS We Included 42 HTx recipients at a median age of 65 years [interquartile range (IQR) 58–70]. At baseline, the median of 27 days (IQR 13–42) before the third dose and the median titre of the whole group was 18 U/ml (IQR 4–130). Only 14 patients (33%) were S-IgG seropositive. After the third dose, the proportion of seropositive patients increased significantly to 57% (P = 0.05) and the median titre increased significantly to 633 U/ml (IQR 7–6104, P < 0.0001). Younger age at HTx (OR per 1-year decrease 1.07, P = 0.05), low tacrolimus serum level (OR per 1-unit decrease 2.28, P = 0.02), mammalian target of rapamycin use (OR 13.3, P = 0.003), lack of oral steroids use (OR 4.17, P = 0.04) and lack of calcineurin inhibitor use (71% of responders vs 100% non-responders received calcineurin inhibitors, P = 0.01) were predictors of seropositive result after the third dose. However, no significant association was detected following adjustment for baseline S-IgG titre. CONCLUSIONS Third-dose booster of BNT162b2 vaccine significantly increased immunogenicity among HTx recipients who previously received a two-dose vaccine.

Background We report the first use of Heartmate 3 (HM3) in a Congenitally corrected Transposition of the Great Arteries (ccTGA) as a Systemic Ventricular Assist Device (SVAD) to treat HF. Case presentation A 55 years old man with a Congenitally corrected Transposition of the Great Arteries (ccTGA) a rare condition in which Heart Failure (HF) is a common presentation in adult life and survival without heart transplantation is hardly an option. Systemic Ventricular Assist Device (SVAD) can be an option if an organ does not become available. We present the first ever implantation of HM3 LVAD (Abbott Inc, Chicago IL) implanted to this patient as a bridge to transplantation, demonstrating the safety and feasibility of the procedure. Due to the unique mediastinal configuration, 3D cardiac CT reconstruction should be used for planning the procedure—intra ventricular placement of the inflow as well as mediastinal placemat of the outflow and pump. Conclusions This successful first use of HM3 as a SVAD for ccTGA patients, opens a novel treatment option for these patients as a bridge for heart transplant or as definitive treatment.

[Abstract] The improvement in left ventricular assist device (LVAD) technology and scarcity of donor hearts have increased dramatically the population of the LVAD-supported patients and the probability of those patients to present to the emergency department with expected and non-expected device-related and patient-device interaction complications. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to suffer from other co-morbidities common in the older population. In this second part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the LVAD-supported patient presenting to the emergency department with bleeding, neurological event, pump thrombosis, chest pain, syncope, and other events are presented. The very challenging issue of declaring death in an LVAD-supported patient, as the circulation is artificially preserved by the device despite no other signs of life, is also discussed in detail.

Endothelial microvascular dysfunction is a known mechanism of vascular pathology in cardiac amyloidosis (CA). Scientific evidence regarding the possible protective role of the amyloid transthyretin (ATTR) stabilizer, tafamidis, is lacking. Circulating endothelial progenitor cells (cEPCs) have an important role in the process of vascular repair. We aimed to examine the effect of tafamidis on cEPCs.Study population included patients with ATTR-CA. cEPCs were assessed using flow cytometry by the expression of CD34Tafamidis induced the activation of the cEPCs pathway, possibly promoting endothelial repair in ATTR-CA.

Patients with heart failure (HF) are at an increased risk of hospital admissions. The aim of this report is to describe the feasibility, safety and accuracy of a novel wireless left atrial pressure (LAP) monitoring system in patients with HF.The V-LAP Left Atrium Monitoring systEm for Patients With Chronic sysTOlicDiastolic Congestive heart Failure (VECTOR-HF) study is a prospective, multicenter, single-arm, open-label, first-in human clinical trial to assess the safety, performance and usability of the V-LAP system (Vectorious Medical Technologies) in patients with New York Heart Association class III HF. The device was implanted in the interatrial septum via a percutaneous, trans-septal approach guided by fluoroscopy and echocardiography. Primary endpoints included the successful deployment of the implant, the ability to perform initial pressure measurements and safety outcomes.To date, 24 patients have received implants of the LAP-monitoring device. No device-related complications have occurred. LAP was reported accurately, agreeing well with wedge pressure at 3 months (Lin concordance correlation coefficient = 0.850). After 6 months, New York Heart Association class improved in 40% of the patients (95% CI = 16.4%-63.5%), while the 6-minute walk test distance had not changed significantly (313.9 ± 144.9 vs 232.5 ± 129.9 meters; P = 0.076).The V-LAP left atrium monitoring system appears to be safe and accurate.

OBJECTIVES In this study, we aimed to determine the comparative outcomes of patients supported with continuous-flow left ventricular assist devices (LVADs): HeartMate 2 (HM2), HeartWare (HW) and HeartMate 3 (HM3) in a real-world setting. METHODS The study was an investigator-initiated comparative retrospective analysis of patients who underwent continuous-flow LVAD implantation at our institution between 2008 and 2017. The follow-up duration was 18 months after implantation. RESULTS The study included 105 continuous-flow LVAD-supported patients of whom 51% (n = 54), 24% (25) and 25% (26) underwent implantation of HM2, HW and HM3, respectively. During follow-up, patients who were supported with HM3 versus either HM2 or HW LVADs demonstrated a lower risk of stroke (0% vs 26%, P CONCLUSIONS HM3 device currently presents better prognostic and adverse events profiles when compared with the HM2 or the HW LVADs. A larger-scale head-to-head comparison between the devices is warranted in order to confirm our findings.

A 53-year-old female patient, an active smoker, received a diagnosis in early 2019 of poor-risk, metastatic renal cell carcinoma with invasion of the inferior vena cava and hepatic veins. Pre-treatment transthoracic echocardiography (TTE) revealed thrombotic involvement of the right atrium with

The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re-interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium-glucose co-transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter-defibrillators in non-ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta-analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure.

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion. Jaarsma, T (corresponding author), Univ Linkoping, Fac Hlth Sci, Kungsgatan 40, S-60174 Norrkoping, Sweden. tiny.jaarsma@liu.se