Impact of malnutrition in patients with severe heart failure.

AIM: The role of malnutrition among patients with severe heart failure (HF) is not well established. We evaluated the incidence, predictors, and prognostic impact of malnutrition in patients with severe HF. METHODS AND RESULTS: Nutritional status was measured using the geriatric nutritional risk index (GNRI), based on body weight, height and serum albumin concentration, with malnutrition defined as GNRI ≤98. It was assessed in consecutive patients with severe HF, defined by at least one high-risk 'I NEED HELP' marker, enrolled at four Italian centres between January 2020 and November 2021. The primary endpoint was all-cause mortality. A total of 510 patients with data regarding nutritional status were included in the study (mean age 74 ± 12 years, 66.5% male). Among them, 179 (35.1%) had GNRI ≤98 (malnutrition). At multivariable logistic regression, lower body mass index (BMI) and higher levels of natriuretic peptides (B-type natriuretic peptide [BNP] > median value [685 pg/ml] or N-terminal proBNP > median value [5775 pg/ml]) were independently associated with a higher likelihood of malnutrition. Estimated rates of all-cause death at 1 year were 22.4% and 41.1% in patients without and with malnutrition, respectively (log-rank p < 0.001). The impact of malnutrition on all-cause mortality was confirmed after multivariable adjustment for relevant covariates (adjusted hazard ratio 2.03, 95% confidence interval 1.43-2.89, p < 0.001). CONCLUSION: In a contemporary, real-world, multicentre cohort of patients with severe HF, malnutrition (defined as GNRI ≤98) was common and independently associated with an increased risk of mortality. Lower BMI and higher natriuretic peptides were identified as predictors of malnutrition in these patients.

Prognostic value of hypochloremia on mortality in patients with heart failure: a systematic review and meta-analysis.

AIMS: Electrolyte imbalances are common in patients with heart failure. Several studies have shown that a low serum chloride level is associated with adverse outcomes in hospitalized patients with acute heart failure and in outpatients with chronic heart failure. We performed a systematic review and meta-analysis to assess the association of hypochloremia with all-cause mortality in patients with heart failure. METHODS: Data search was conducted from inception through 1 February 2023, using the following MeSH terms: ('chloride' OR 'hypochloremia') AND 'heart failure'. Studies evaluating the association between serum chloride and all-cause mortality in patients with heart failure were included. The predefined primary outcome was all-cause mortality. Pooled hazard ratios and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effects model; fixed-effects model and leave-one-out sensitivity analyses were also performed. RESULTS: A total of 15 studies, involving 25 848 patients, were included. The prevalence of hypochloremia ranged from 8.6 to 31.5%. Follow-up time ranged from 6 to 67 months. Hypochloremia as a categorical variable was associated with an increased risk of all-cause mortality [hazard ratio 1.56; 95% confidence interval (CI) 1.38-1.75; P  < 0.001]. As a continuous variable, serum chloride was associated with all-cause mortality (hazard ratio per mmol/l decrease in serum chloride: 1.06; 95% CI 1.05-1.07; P  < 0.001). Results were confirmed by using several sensitivity analyses. CONCLUSION: Hypochloremia exhibits a significant prognostic value in patients with heart failure. Serum chloride can be used as an effective tool for risk stratifying in patients with heart failure.

Frailty according to the 2019 HFA-ESC definition in patients at risk for advanced heart failure: Insights from the HELP-HF registry.

AIMS: Frailty is highly prevalent in patients with heart failure (HF), but a concordant definition of this condition is lacking. The Heart Failure Association of the European Society of Cardiology (HFA-ESC) proposed in 2019 a new multi-domain definition of frailty, but it has never been validated. METHODS AND RESULTS: Patients from the HELP-HF registry were stratified according to the number of HFA-ESC frailty domains fulfilled and to the cumulative deficits frailty index (FI) quintiles. Prevalence of frailty and of each domain was reported, as well as the rate of the composite of all-cause death and HF hospitalization, its single components, and cardiovascular death in each group and quintile. Among 854 included patients, 37 (4.3%), 206 (24.1%), 365 (42.8%), 217 (25.4%), and 29 (3.4%) patients fulfilled zero, one, two, three, or four domains, respectively, while 179 patients had a FI < 0.21 and were considered not frail. The 1-year risk of adverse events increased proportionally to the number of domains fulfilled (for each criterion increase, all-cause death or HF hospitalization: hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.27-1.62; all-cause death: HR 1.72, 95% CI 1.46-2.02, HF hospitalizations: subHR 1.21, 95% CI 1.04-1.31; cardiovascular death: HR 1.77, 95% CI 1.45-2.15). Consistent results were found stratifying the cohort for FI quintiles. The FI as a continuous variable demonstrated higher discriminative ability than the number of domains fulfilled (area under the curve = 0.68 vs. 0.64, p = 0.004). CONCLUSION: Frailty in patients at risk for advanced HF, assessed via a multi-domain approach and the FI, is highly prevalent and identifies those at increased risk of adverse events. The FI was found to be slightly more effective in identifying patients at increased risk of mortality.

Real-world data of patients affected by advanced heart failure treated with implantable cardioverter defibrillator and left ventricular assist device: Results of a multicenter observational study.

BACKGROUND: Left ventricular assist device (L-VAD) implantation is increasingly used in patients with heart failure (HF) and most patients also have an implantable cardioverter defibrillator (ICD). Limited data are available on the incidence of ICD therapies and complications in this special setting. The aim of this study was to analyze the real-world incidence and predictors of ICD therapies, complications and interactions between ICD and L-VAD. METHODS: We conducted a multicenter retrospective observational study in patients with advanced HF implanted with ICD and a continuous-flow L-VAD, followed-up in five advanced HF centers in Northern Italy. RESULTS: A total of 234 patients (89.7% male, median age 59, 48.3% with ischemic etiology) were enrolled. After a median follow-up of 21 months, 66 patients (28.2%) experienced an appropriate ICD therapy, 22 patients (9.4%) an inappropriate ICD therapy, and 17 patients (7.3%) suffered from an interaction between ICD and L-VAD. The composite outcome of all ICD-related complications was reported in 41 patients (17.5%), and 121 (51.7%) experienced an L-VAD-related complication. At multivariable analysis, an active ventricular tachycardia (VT) zone and a prior ICD generator replacement were independent predictors of ICD therapies and of total ICD-related complications, respectively. CONCLUSIONS: Real-world patients with both L-VAD and ICD experience a high rate of ICD therapies and complications. Our findings suggest the importance of tailoring device programming in order to minimize the incidence of unnecessary ICD therapies, thus sparing the need for ICD generator replacement, a procedure associated to a high risk of complications.

GLP-1-ra and heart failure-related outcomes in patients with and without history of heart failure: an updated systematic review and meta-analysis.

AIMS: Glucagon-like peptide-1 receptor agonists (GLP1-ra) have shown to reduce cardiovascular (CV) events in patients with diabetes, including heart failure (HF) hospitalizations. However, whether such benefit consistently occurs in patients with history of HF remains uncertain. We performed a systematic review and meta-analysis to assess the impact of GLP1-ra on CV outcomes in patients with and without HF history. METHODS AND RESULTS: All randomized, placebo-controlled trials evaluating GLP1-ra and reporting CV outcomes stratified by HF history were searched in Pubmed from inception to November 12th, 2023. The primary outcome was HF hospitalizations. Secondary outcomes included CV death, the composite of CV death and hospitalizations for HF, and major adverse cardiovascular events (MACE). Hazard ratio (HR) and 95% confidence interval (CIs) were used as effect estimates and calculated with a random-effects model. 68,653 patients (GLP1-ra = 34,301, placebo = 34,352) from 10 trials were included. GLP1-ra reduced HF hospitalization (no HF: HR = 0.79, 95% CI 0.63-0.98; HF: HR = 1.00, 95% CI 0.82-1.24, pinteraction = 0.12), CV death (no HF: HR = 0.81, 95% CI 0.71-0.92; HF: HR = 0.97, 95% CI 0.81-1.15, pinteraction = 0.11), and the composite of HF hospitalizations and CV death (no HF: HR = 0.80, 95% CI 0.72-0.89; HF: HR = 1.00 95% CI 0.88-1.15, pinteraction = 0.010) only in patients without history of HF, despite a significant interaction between HF history and treatment effect was detected only for the latter. MACE were reduced in both subgroups without significant interaction between HF history and treatment effect (no HF: HR = 0.86, 95% CI 0.78-0.96; HF: HR = 0.83, 95% CI 0.72-0.95, pinteraction = 0.69). CONCLUSION: GLP1-ra do not decrease HF-hospitalization risk, despite a potential benefit in patients without history of HF, but are effective in reducing ischemic events irrespective of the presence of HF. PROSPERO-registered (CRD42022371264).

Characteristics and outcomes of patients with tricuspid regurgitation and advanced heart failure.

AIMS: To evaluate the role of tricuspid regurgitation in advanced heart failure. METHODS: The multicenter observational HELP-HF registry enrolled consecutive patients with heart failure and at least one 'I NEED HELP' criterion evaluated at four Italian centers between January 2020 and November 2021. Patients with no data on tricuspid regurgitation and/or receiving tricuspid valve intervention during follow-up were excluded. The population was stratified by no/mild tricuspid regurgitation vs. moderate tricuspid regurgitation vs. severe tricuspid regurgitation. Variables independently associated with tricuspid regurgitation, as well as the association between tricuspid regurgitation and clinical outcomes were investigated. The primary outcome was all-cause mortality. RESULTS: Among the 1085 patients included in this study, 508 (46.8%) had no/mild tricuspid regurgitation, 373 (34.4%) had moderate tricuspid regurgitation and 204 (18.8%) had severe tricuspid regurgitation. History of atrial fibrillation, any prior valve surgery, high dose of furosemide, preserved left ventricular ejection fraction, moderate/severe mitral regurgitation and pulmonary hypertension were found to be independently associated with an increased likelihood of severe tricuspid regurgitation. Estimated rates of 1-year all-cause death were of 21.4, 24.5 and 37.1% in no/mild tricuspid regurgitation, moderate tricuspid regurgitation and severe tricuspid regurgitation, respectively (log-rank P  < 0.001). As compared with nonsevere tricuspid regurgitation, severe tricuspid regurgitation was independently associated with a higher risk of all-cause mortality (adjusted hazard ratio 1.38, 95% confidence interval 1.01-1.88, P  = 0.042), whereas moderate tricuspid regurgitation did not. CONCLUSION: In a contemporary, real-world cohort of patients with advanced heart failure, several clinical and echocardiographic characteristics are associated with an increased likelihood of severe tricuspid regurgitation. Patients with severe tricuspid regurgitation have an increased risk of mortality.

Clinical burden and predictors of non-cardiovascular mortality and morbidity in advanced heart failure.

BACKGROUND: The changing demographic of heart failure (HF) increases the exposure to non-cardiovascular (non-CV) events. We investigated the distribution of non-CV mortality/morbidity and the characteristics associated with higher risk of non-CV events in patients with advanced HF. METHODS: Patients from the HELP-HF registry were stratified according to the number of 2018 HFA-ESC criteria for advanced HF. Endpoints were non-CV mortality and non-CV hospitalization. Competing risk analyses were performed assessing the association between HFA-ESC criteria and study outcomes and the additional predictors of non-CV endpoints. RESULTS: One thousand one hundred and forty-nine patients were included (median age 77 years-IQR 69-83). At 6, 12, 18 and 22 months, cumulative incidence of CV vs non-CV mortality was 13% vs 5%, 17% vs 8%, 20% vs 12%, 23% vs 12%, and of CV vs non-CV hospitalization was 26% vs 11%, 38% vs 17%, 45% vs 20%, 50% vs 21%. HFA-ESC criteria were associated with increasing adjusted risk of CV death, whereas no association was observed for CV hospitalization, non-CV death and non-CV hospitalization. Predictors of non-CV death were age, chronic obstructive pulmonary disease, dementia, preserved ejection fraction, >1 HF hospitalization and hemoglobin. CONCLUSIONS: Patients with advanced HF are exposed to high, even though not predominant, burden of non-CV outcomes. HFA-ESC criteria aid to stratify the risk of CV death, but are not associated with lower competing risk of non-CV outcomes. Alternative factors can be useful to define the patients with advanced HF at risk of non-CV events in order to better select patients for treatments specifically reducing CV risk.

Guideline-directed medical therapy in severe heart failure with reduced ejection fraction: An analysis from the HELP-HF registry.

AIM: Persistent symptoms despite guideline-directed medical therapy (GDMT) and poor tolerance of GDMT are hallmarks of patients with advanced heart failure (HF) with reduced ejection fraction (HFrEF). However, real-world data on GDMT use, dose, and prognostic implications are lacking. METHODS AND RESULTS: We included 699 consecutive patients with HFrEF and at least one 'I NEED HELP' marker for advanced HF enrolled in a multicentre registry. Beta-blockers (BB) were administered to 574 (82%) patients, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor-neprilysin inhibitors (ACEi/ARB/ARNI) were administered to 381 (55%) patients and 416 (60%) received mineralocorticoid receptor antagonists (MRA). Overall, ≥50% of target doses were reached in 41%, 22%, and 56% of the patients on BB, ACEi/ARB/ARNI and MRA, respectively. Hypotension, bradycardia, kidney dysfunction and hyperkalaemia were the main causes of underprescription and/or underdosing, but up to a half of the patients did not receive target doses for unknown causes (51%, 41%, and 55% for BB, ACEi/ARB/ARNI and MRA, respectively). The proportions of patients receiving BB and ACEi/ARB/ARNI were lower among those fulfilling the 2018 HFA-ESC criteria for advanced HF. Treatment with BB and ACEi/ARB/ARNI were associated with a lower risk of death or HF hospitalizations (adjusted hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48-0.84, and HR 0.74, 95% CI 0.58-0.95, respectively). CONCLUSIONS: In a large, real-world, contemporary cohort of patients with severe HFrEF, with at least one marker for advanced HF, prescription and uptitration of GDMT remained limited. A significant proportion of patients were undertreated due to unknown reasons suggesting a potential role of clinical inertia either by the prescribing healthcare professional or by the patient. Treatment with BB and ACEi/ARB/ARNI was associated with lower mortality/morbidity.

Role of ejection fraction in patients at risk for advanced heart failure: insights from the HELP-HF registry.

AIMS: Patients with heart failure (HF) with reduced ejection fraction (EF) (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF) may all progress to advanced HF, but the impact of EF in the advanced setting is not well established. Our aim was to assess the prognostic impact of EF in patients with at least one 'I NEED HELP' marker for advanced HF. METHODS AND RESULTS: Patients with HF and at least one high-risk 'I NEED HELP' criterion from four centres were included in this analysis. Outcomes were assessed in patients with HFrEF (EF ≤ 40%), HFmrEF (EF 41-49%), and HFpEF (EF ≥ 50%) and with EF analysed as a continuous variable. The prognostic impact of medical therapy for HF in patients with EF < 50% and EF > 50% was also evaluated. All-cause death was the primary endpoint, and cardiovascular death was a secondary endpoint. Among 1149 patients enrolled [mean age 75.1 ± 11.5 years, 67.3% males, 67.6% hospitalized, median follow-up 260 days (inter-quartile range 105-390 days)], HFrEF, HFmrEF, and HFpEF were observed in 699 (60.8%), 122 (10.6%), and 328 (28.6%) patients, and 1 year mortality was 28.3%, 26.2%, and 20.1, respectively (log-rank P = 0.036). As compared with HFrEF patients, HFpEF patients had a lower risk of all-cause death [adjusted hazard ratio (HRadj ) 0.67, 95% confidence interval (CI) 0.48-0.94, P = 0.022], whereas no difference was noted for HFmrEF patients. After multivariable adjustment, a lower risk of all-cause death (HRadj for 5% increase 0.94, 95% CI 0.89-0.99, P = 0.017) and cardiovascular death (HRadj for 5% increase 0.94, 95% CI 0.88-1.00, P = 0.049) was observed at higher EF values. Beta-blockers and renin-angiotensin system inhibitors or sacubitril/valsartan were associated with lower mortality in both EF < 50% and EF ≥ 50% groups. CONCLUSIONS: Among patients with HF and at least one 'I NEED HELP' marker for advanced HF, left ventricular EF is still of prognostic value.

Prognostic role of mitral regurgitation in patients with advanced heart failure.

AIM: The impact of mitral regurgitation (MR) in patients with advanced heart failure (HF) is poorly known. We aimed to evaluate the impact of MR on clinical outcomes of a real-world, contemporary, multicentre population with advanced HF. METHODS: The HELP-HF registry enrolled patients with HF and at least one "I NEED HELP" criterion, at four Italian centres between January 2020 and November 2021. The population was stratified by none/mild MR vs. moderate MR vs. severe MR. Outcomes of interest were all-cause, cardiovascular (CV) death, the composite of all-cause death or first HF hospitalization, first HF hospitalization and recurrent HF hospitalizations. RESULTS: Among 1079 patients, 429 (39.8%) had none/mild MR, 443 (41.1%) had moderate MR and 207 (19.2%) had severe MR. Patients with severe MR were most likely to be inpatients, present with cardiogenic shock, need intravenous loop diuretics and inotropes/vasopressors, have lower ejection fraction and higher natriuretic peptides. Estimated rates of all-cause death, CV death, and the composite of all-cause death or first HF hospitalization at 1 year increased with increasing MR severity. Compared with no/mild MR, severe MR was independently associated with an increased risk of CV death (adjusted HR 1.61, 95% CI 1.04-2.51, p = 0.033) and recurrent HF hospitalizations (adjusted HR 1.49, 95% CI 1.08-2.06, p = 0.015), but not with and increased risk of all-cause death, first HF hospitalization and composite outcome. CONCLUSIONS: In unselected patients with advanced HF, severe MR was common and independently associated with an increased risk of CV death and of recurrent HF hospitalizations.

Clinical and prognostic implications of heart failure hospitalization in patients with advanced heart failure.

BACKGROUND: Hospitalization is associated with poor outcomes in patients with heart failure, but its prognostic role in advanced heart failure is still unsettled. We evaluated the prognostic role of heart failure hospitalization in patients with advanced heart failure. METHODS: The multicenter HELP-HF registry enrolled consecutive patients with heart failure and at least one high-risk 'I NEED HELP' marker. Characteristics and outcomes were compared between patients who were hospitalized for decompensated heart failure (inpatients) or not (outpatients) at the time of enrolment. The primary endpoint was the composite of all-cause mortality or first heart failure hospitalization. RESULTS: Among the 1149 patients included [mean age 75.1 ±â€Š11.5 years, 67.3% men, median left ventricular ejection fraction (LVEF) 35% (IQR 25-50%)], 777 (67.6%) were inpatients at the time of enrolment. As compared with outpatients, inpatients had lower LVEF, higher natriuretic peptides and a worse clinical profile. The 1-year rate of the primary endpoint was 50.9% in inpatients versus 36.8% in outpatients [crude hazard ratio 1.70, 95% confidence interval (CI) 1.39-2.07, P < 0.001]. At multivariable analysis, inpatient status was independently associated with a higher risk of the primary endpoint (adjusted hazard ratio 1.54, 95% CI 1.23-1.93, P < 0.001). Among inpatients, the independent predictors of the primary endpoint were older age, lower SBP, heart failure association criteria for advanced heart failure and glomerular filtration rate 30 ml/min/1.73 m2 or less. CONCLUSION: Hospitalization for heart failure in patients with at least one high-risk 'I NEED HELP' marker is associated with an extremely poor prognosis supporting the need for specific interventions, such as mechanical circulatory support or heart transplantation.

Detailed Assessment of the "I Need Help" Criteria in Patients With Heart Failure: Insights From the HELP-HF Registry.

BACKGROUND: The "I Need Help" markers have been proposed to identify patients with advanced heart failure (HF). We evaluated the prognostic impact of these markers on clinical outcomes in a real-world, contemporary, multicenter HF population. METHODS: We included consecutive patients with HF and at least 1 high-risk "I Need Help" marker from 4 centers. The impact of the cumulative number of "I Need Help" criteria and that of each individual "I Need Help" criterion was evaluated. The primary end point was the composite of all-cause mortality or first HF hospitalization. RESULTS: Among 1149 patients enrolled, the majority had 2 (30.9%) or 3 (22.6%) "I Need Help" criteria. A higher cumulative number of "I Need Help" criteria was independently associated with a higher risk of the primary end point (adjusted hazard ratio for each criterion increase, 1.19 [95% CI, 1.11-1.27]; P<0.001), and patients with >5 criteria had the worst prognosis. Need of inotropes, persistently high New York Heart Association classes III and IV or natriuretic peptides, end-organ dysfunction, >1 HF hospitalization in the last year, persisting fluid overload or escalating diuretics, and low blood pressure were the individual criteria independently associated with a higher risk of the primary end point. CONCLUSIONS: In our HF population, a higher number of "I Need Help" criteria was associated with a worse prognosis. The individual criteria with an independent impact on mortality or HF hospitalization were need of inotropes, New York Heart Association class or natriuretic peptides, end-organ dysfunction, multiple HF hospitalizations, persisting edema or escalating diuretics, and low blood pressure.

Bridging the gap in the symptomatic heart failure patient journey: insights from the Italian scenario.

BACKGROUND: The prognosis for heart failure (HF) patients remains poor, with a high mortality rate, and a marked reduction in quality of life (QOL) and functional status. This study aims to explore the ongoing needs of HF management and the epidemiology of patients followed by Italian HF clinics, with a specific focus on cardiac contractility modulation (CCM). RESEARCH DESIGN AND METHODS: Data from patients admitted to 14 HF outpatients clinics over 4 weeks were collected and compared to the results of a survey open to physicians involved in HF management operating in Italian centers. RESULTS: One hundred and five physicians took part in the survey. Despite 94% of patients receive a regular follow-up every 3-6 months, available therapies are considered insufficient in 30% of cases. Physicians reported a lack of treatment options for 23% of symptomatic patients with reduced ejection fraction (EF) and for 66% of those without reduced EF. Approximately 3% of HF population (two patients per month per HF clinic) meets the criteria for immediate CCM treatment, which is considered a useful option by 15% of survey respondents. CONCLUSIONS: Despite this relatively small percentage, considering total HF population, CCM could potentially benefit numerous HF patients, particularly the elderly, by reducing hospitalizations, improving functional capacity and QOL.

Ischemic Etiology in Advanced Heart Failure: Insight from the HELP-HF Registry.

In patients with advanced heart failure (HF), defined according to the presence of at least one I-NEED-HELP criterium, the updated 2018 Heart Failure Association of the European Society of Cardiology (HFA-ESC) criteria for advanced HF identify a subgroup of patients with HF with worse prognosis, but whether ischemic etiology has a relevant prognostic impact in this very high-risk cohort is unknown. Patients from the HELP-HF registry were stratified according to ischemic etiology and presence of advanced HF based on 2018 HFA-ESC criteria. The primary end point was a composite of all-cause death and HF hospitalization at 1 year. Secondary end points were all-cause death, HF hospitalization, and cardiovascular death at 1 year. Ischemic etiology was a leading cause of HF, in both patients with advanced and nonadvanced HF (46.1% and 42.4%, respectively, p = 0.337). The risk of the primary end point (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.58) and all-cause mortality (HR 1.37, 95% CI 1.06 to 1.76) was increased in ischemic as compared with nonischemic patients. The risk of the primary end point was consistently higher in ischemic patients in both patients with advanced and nonadvanced HF (advanced HF, HR 1.50 95% CI 1.04 to 2.16; nonadvanced HF, HR 1.25 95% CI 1.01 to 1.56, pinteraction = 0.333), driven by an increased risk of mortality, mainly because of cardiovascular causes. In conclusion, ischemic etiology is the most common cause of HF in patients with at least one I-NEED-HELP marker and with or without advanced HF as defined by the 2018 HFA-ESC definition. In both patients with advanced and not-advanced HF, ischemic etiology carried an increased risk of worse prognosis.

Atrial arrhythmias and heart failure: A "modern view" of an old paradox.

BACKGROUND: Heart failure (HF) and atrial arrhythmias (AAs) are two clinical conditions that characterize the daily clinical practice of cardiologists. In this perspective review, we analyze the shared etiopathogenetic pathways of atrial arrhythmias, which are the most common cause of atrial arrhythmias-induced cardiomyopathy (AACM) and HF. HYPOTHESIS: The aim is to explore the pathophysiology of these two conditions considering them as a "unicum", allowing the definition of a cardiovascular continuum where it is possible to predict the factors and to identify the patient phenotype most at risk to develop HF due to atrial arrhythmias. METHODS: Potentially eligible articles, identified from the Electronic database (PubMed), and related references were used for a literature search that was conducted between January 2022 and January 2023. Search strategies were designed to identify articles that reported atrial arrhythmias in association with heart failure and vice versa. For the search we used the following keywords: atrial arrhythmias, atrial fibrillation, heart failure, arrhythmia-induced cardiomyopathy, tachycardiomyopathy. We identified 620 articles through the electronic database search. Out of the 620 total articles we removed 320 duplicates, thus selecting 300 eligible articles. About 150 titles/abstracts were excluded for the following reasons: no original available data, no mention of atrial arrhythmias and heart failure crosstalk, very low quality analysis or evidence. We excluded also non-English articles. When multiple articles were published on the same topic, the articles with the most complete set of data were considered. We preferentially included all papers that could provide the best evidence in the field. As a result, the present review article is based on a final number of 104 references. RESULTS: While the pathophysiology of AACM and Heart Failure with reduced ejection fraction (HFrEF) has been studied in detail over the years, the causal link between atrial arrhythmias and heart failure with Preserved Ejection Fraction (HFpEF) has been often subject of interest. HFpEF is strictly related to AAs, which has always been considered significant risk factor. In this review we described the pathophysiological links between atrial fibrillation and heart failure. Furthermore, we illustrated and discussed the preclinical and clinical predicting factors of AF and HFpEF, and the corresponding targets of the available therapeutic agents. Finally, we outlined the patient phenotype at risk of developing AF and HFpEF (Central Illustration). CONCLUSIONS: In this review, we underline how these two clinical conditions (AF and HFpEF) represent a "unicum" and, therefore, should be considered as a single disease that can manifest itself in the same phenotype of patients but at different times. Furthermore, considering that today we have few therapeutic strategies to treat these patients, it would be good to make an early diagnosis in the initial stages of the disease or intervene even before the development of signs and symptoms of HF. This is possible only by paying greater attention to patients with predisposing factors and carrying out a targeted screening with the correct diagnostic methods. A systemic approach aimed at improving the immuno-metabolic profile of these patients by lowering the body mass index, threatening the predisposing factors, lowering the mean heart rate and reducing the sympathetic nervous system activation is the key strategy to reduce the clinical impact of this disease.

Edge-to-edge percutaneous mitral repair for functional ischaemic and non-ischaemic mitral regurgitation: a systematic review and meta-analysis.

AIM: Randomized controlled trials comparing the use of the MitraClip device in addition to guideline directed medical therapy (GDMT) to GDMT alone in patients with secondary mitral regurgitation (MR) have shown conflicting results. However, if these differences could be due to the underlying MR aetiology is still unknown. Therefore, we aimed to evaluate if the effects of percutaneous edge-to-edge repair with MitraClip implantation could differ in patients with ischaemic (I-MR) and non-ischaemic mitral regurgitation (NI-MR). METHODS AND RESULTS: PubMed, Embase, BioMed Central, and the Cochrane Central Register of Controlled Trials were searched for all studies including patients with secondary MR treated with the MitraClip device. Data were pooled using a random-effects model. Primary endpoint was the composite of all-cause death and heart failure-related hospitalization. Secondary endpoints were the single components of the primary endpoint, New York Heart Association functional Classes III and IV, and mitral valve re-intervention. Seven studies enrolling 2501 patients were included. Patients with I-MR compared with patients with NI-MR had a similar risk of the primary endpoint (odds ratio: 1.17; 95% confidence interval: 0.93 to 1.46; I2 : 0%). The risk of all-cause death was increased in patients with I-MR (odds ratio: 1.31; 95% confidence interval: 1.07 to 1.62; I2 : 0%), while no differences were observed between the two groups in terms of the other secondary endpoints. CONCLUSIONS: The risk of mortality after MitraClip implantation is lower in patients with NI-MR than in those with I-MR. No absolute differences in the risk of heart failure related hospitalization were observed between groups.

New Onset of Eosinophilic Granulomatosis with Polyangiitis Following mRNA-Based COVID-19 Vaccine.

Anti-SARS-CoV-2 vaccines are safe and effective, also in individuals with allergic and immune-mediated diseases (IMDs). There are reports suggesting that vaccines may be able to trigger de-novo or exacerbate pre-existing IMDs in predisposed individuals. Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis characterized by asthma, eosinophilia, and eosinophil-rich granulomatous inflammation in various tissues. We describe the case of a 63-year-old man who experienced cardiac, pulmonary, and neurological involvement one day after the administration of the booster dose of anti-SARS-CoV-2 vaccine (mRNA-1273). A diagnosis of EGPA was made and the patient was treated with high-dose steroids and cyclophosphamide, with a good clinical response. Interestingly, our patient had experienced a significant worsening of his pre-existing asthma six months earlier, just after the first two vaccine shots with the ChAdOx1 anti-SARS-CoV-2 vaccine. It is impossible to know whether our patient would have had developed EGPA following natural SARS-CoV-2 infection or at some point in his life regardless of infectious stimuli. Nevertheless, our report may suggest that caution should be paid during the administration of additional vaccine doses in individuals who experienced an increase in IMD severity that persisted over time following previous vaccine shots.

Prognostic impact of the updated 2018 HFA-ESC definition of advanced heart failure: results from the HELP-HF registry.

AIMS: The Heart Failure Association of the European Society of Cardiology (HFA-ESC) proposed a definition of advanced heart failure (HF) that has not been validated, yet. We assessed its prognostic impact in a consecutive series of patients with high-risk HF. METHODS AND RESULTS: The HELP-HF registry enrolled consecutive patients with HF and at least one high-risk 'I NEED HELP' marker, evaluated at four Italian centres between 1st January 2020 and 30th November 2021. Patients meeting the HFA-ESC advanced HF definition were compared to patients not meeting this definition. The primary endpoint was the composite of all-cause mortality or first HF hospitalization. Out of 4753 patients with HF screened, 1149 (24.3%) patients with at least one high-risk 'I NEED HELP' marker were included (mean age 75.1 ± 11.5 years, 67.3% male, median left ventricular ejection fraction [LVEF] 35% [interquartile range 25%-50%]). Among them, 193 (16.8%) patients met the HFA-ESC advanced HF definition. As compared to others, these patients were younger, had lower LVEF, higher natriuretic peptides and a worse clinical profile. The 1-year rate of the primary endpoint was 69.3% in patients with advanced HF according to the HFA-ESC definition versus 41.8% in the others (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.82-2.74, p < 0.001). The prognostic impact of the HFA-ESC advanced HF definition was confirmed after multivariable adjustment for relevant covariates (adjusted HR 1.98, 95% CI 1.57-2.50, p < 0.001). CONCLUSIONS: The HFA-ESC advanced HF definition had a strong prognostic impact in a contemporary, real-world, multicentre high-risk cohort of patients with HF.

[ANMCO Position paper: Care pathway for advanced heart failure patients candidate for heart transplantation/ventricular assist device]. / Position paper ANMCO: Percorso assistenziale del paziente con insufficienza cardiaca avanzata candidabile a trapianto/assistenza ventricolare meccanica.

Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.