Haptoglobin Administration for Intravascular Hemolysis: A Systematic Review.

Introduction Exogenous haptoglobin administration may enhance plasma-free hemoglobin (pfHb) clearance during hemolysis, and reduce its end-organ damage: we sought to systematically review and summarize available evidence on the use of haptoglobin as a treatment for hemolysis of any cause. Methods We included studies describing haptoglobin administration as treatment or prevention of hemolysis-related complications. Only studies with a control group reporting at least one of the outcomes of interest were included in the quantitative synthesis. Primary outcome was the change in pfHb concentration 1 hour after haptoglobin infusion. Results Among 573 articles, 13 studies were included in the review (677 patients, 52.8% received haptoglobin). Median initial haptoglobin intravenous bolus was 4000 (2000, 4000) IU. Haptoglobin was associated with lower pfHb 1 hour (SMD -11.28; 95% CI -15.80 to -6.75; p<0.001) and 24 hours (SMD -2.65; 95% CI -4.73 to -0.57; p=0.001) after infusion. There was no difference in all-cause mortality between haptoglobin-treated patients and control group (OR 1.41; 95% CI 0.49 to 4.95; p=0.520). Haptoglobin was associated with a lower incidence of acute kidney injury (OR 0.64; 95% CI 0.44-0.93; p=0.020). No adverse events or side effects associated with haptoglobin use were reported. Conclusions Haptoglobin administration has been used in patients with hemolysis from any cause to treat or prevent hemolysis-associated adverse events. Haptoglobin may reduce levels of pfHb and preserve kidney function without increase in adverse events.

Recognizing patients as candidates for temporary mechanical circulatory support along the spectrum of cardiogenic shock.

A growing body of evidence indicates that the benefits of temporary mechanical circulatory support (tMCS) in patients with cardiogenic shock (CS) is dependent on its aetiology and timing of implantation. As such, appropriate diagnosis, screening, selection, and treatment is crucial to achieving good outcomes with tMCS. Here, the latest guidance on CS phenotypes and diagnostics for correctly identifying tMCS candidates is discussed. This includes comprehensive overviews of patient screening with attention given to differences in CS presentation between the sexes, and contraindications for mechanical circulatory support.

Monitoring MCS patients on the intensive care unit: integrating haemodynamic assessment, laboratory data, and imaging techniques for timely detection of deterioration and recovery.

Monitoring of the patient supported with a temporary mechanical circulatory support (tMCS) is crucial in achieving the best possible outcome. Monitoring is a continuous and labour-intensive process, as cardiogenic shock (CS) patients can rapidly deteriorate and may require new interventions within a short time period. Echocardiography and invasive haemodynamic monitoring form the cornerstone of successful tMCS support. During monitoring, it is particularly important to ensure that adequate end-organ perfusion is achieved and maintained. Here, we provide a comprehensive overview of best practices for monitoring the CS patient supported by a micro-axial flow pump, veno-arterial extracorporeal membrane oxygenation, and both devices simultaneously (ECMELLA approach). It is a complex process that encompasses device control, haemodynamic control and stabilization, monitoring of interventions, and assessment of end-organ function. The combined, continuous, and preferably protocol-based approach of echocardiography, evaluation of biomarkers, end-organ assessment, and haemodynamic parameters is crucial in assessing this critically ill CS patient population.

Bedside intra-aortic balloon pump insertion in cardiac intensive care unit: A single-center experience.

BACKGROUND: In contemporary Cardiac Intensive Care Unit (CICU), bedside intra-aortic balloon pump (IABP) insertion under echocardiographic guidance may be an attractive option for selected patients with cardiogenic shock (CS). Currently available data on this approach are limited. AIM: This study aimed to assess the feasibility and safety of bedside IABP insertion, as compared to fluoroscopic-guided insertion in the Catheterization Laboratory (CathLab), and to describe the clinical features of patients receiving bedside IABP insertion using a standardized technique in real-world CICU practice. METHODS: We prospectively evaluated all patients admitted the CICU who received transfemoral IABP between June 2020 and October 2021. The overall study cohort was divided according to implant strategy in bedside and CathLab groups. The primary outcome was correct radiographic IABP positioning at the first bedside chest X-ray obtained after insertion. Secondary outcomes included IABP-related complications. RESULTS: Among 115 patients, bedside IABP insertion was performed in 35 (30.4%) cases, mainly presenting with CS-related to acute decompensated heart failure (ADHF) (68.6 vs 33.8%; p < 0.001), with lower LVEF, higher proportion of right ventricular involvement and higher need of inotropes/vasopressors, compared to those receiving CathLab insertion. Bedside IABP insertion resulted feasible and safe, with similar rates of correct IABP positioning (82.9 vs. 82.5%; p = 0.963) and IABP-related major vascular complications (5.7 vs. 5.0%; p = 0.874), as compared to CathLab positioning. CONCLUSION: This study suggests the feasibility and safety of bedside IABP insertion, which could be of relevant interest in patients with ADHF-related CS who may not need coronary angiography or other urgent CathLab procedures.

Amiodarone in ventricular arrhythmias: still a valuable resource?

Ventricular arrhythmias still represent an important cause of morbidity and mortality, especially in patients with heart failure and reduced left ventricular ejection fraction. Amiodarone is a Class III Vaughan-Williams anti-arrhythmic drug widely used in ventricular arrhythmias for its efficacy and low pro-arrhythmogenic effect. On the other hand, a significant limitation in its use is represented by toxicity. In this review, the pharmacology of the drug is discussed to provide the mechanistic basis for its clinical use. Moreover, all the latest evidence on its role in different clinical settings is provided, including the prevention of sudden cardiac death, implanted cardioverter defibrillators, ischemic and non-ischemic cardiomyopathies. A special focus is placed on everyday clinical practice learning points, such as dosage, indications, and contraindications from the latest guidelines.

Use of extracorporeal membrane oxygenation in high-risk acute pulmonary embolism: A systematic review and meta-analysis.

Extracorporeal membrane oxygenation (ECMO) represents a therapeutic option for cardiopulmonary support in patients with high-risk pulmonary embolism (PE); however, no definite consensus exists on ECMO use in high-risk PE. Hence, we aim to provide insights into its real-world use pooling together all available published experiences. We performed a systematic review and pooled analysis of all published studies (up to April 17, 2020) investigating ECMO support in high-risk PE. All studies including at least four patients were collectively analyzed. Study outcomes were early all-cause death (primary endpoint) and relevant in-hospital adverse events. A total of 21 studies were included in the pooled analysis (n = 635 patients). In this population (mean age 47.8 ± 17.3 years, 44.5% females), ECMO was indicated for cardiac arrest in 62.3% and immediate ECMO support was pursued in 61.9% of patients. Adjunctive reperfusion therapies were implemented in 57.0% of patients. Pooled estimate rate of early all-cause mortality was 41.1% (95% CI 27.7%-54.5%). The most common in-hospital adverse event was major bleeding, with an estimated rate of 28.6% (95%CI 21.0%-36.3%). At meta-regression analyses, no significant impact of multiple covariates on the primary endpoint was found. In this systematic review of patients who received ECMO for high-risk PE, pooled all-cause mortality was 41.1%. Principal indication for ECMO was cardiac arrest, cannulation was chiefly performed at presentation, and major bleeding was the most common complication.

The impact of the coronary sinus reducer upon left ventricular function in patients with refractory angina pectoris.

OBJECTIVES: To evaluate the impact of coronary sinus (CS) Reducer implantation upon left ventricular (LV) function. BACKGROUND: CS Reducer implantation is associated with symptomatic relief in patients with refractory angina. The effects of the device upon left ventricular function remains unknown. METHODS: Prior to device implantation and at 4-months, resting ventricular volumes and function were measured using cardiac magnetic resonance (CMR). Stress CMR was performed to extract quantitative indices of myocardial perfusion (myocardial perfusion reserve index-MPRI). RESULTS: Nineteen patients (18 males, 66.0 [IQR 56.0-77.0] years), underwent successful Reducer implantation. Sixteen (84%) patients improved by at least 1 CCS class. Four months after Reducer implantation, we noticed a significant improvement in LV ejection fraction (LVEF) (61 [IQR 47-71] to 66 [IQR 57-72] %; p = .009), a reduction in LV end-diastolic volume (LVEDV)/Body surface area (BSA) (65.7 [IQR 57.4-89.6] to 64.7 [IQR 53.7-74.1] mL/m2 ; p = .036) and a reduction in LV end-systolic volume (LVESV)/BSA (28.7 [IQR 18.6-38.8] to 20.0 [IQR 15.0-31.4] mL/m2 ; p = .007). Patients with reduced EF (EF < 50%, n = 6) presented a greater increase of EF at follow up compared to patients with preserved EF (11.3 [IQR 6.5-54.5] vs. 3.8 [IQR 0.6-9.1] %; p = .029). The observed decrease in LVESV/BSA was greater in patients with reduced EF (23.6 [IQR 11.6-33.8] vs. 4.2 [IQR -2.0 to 8.4] mL/m2 ; p = .005). A significant increase in transmural MPRI was observed 4 months after Reducer implantation (p < .011). CONCLUSIONS: CS Reducer improved angina symptoms and improved left ventricular function. The improvement was pronounced in the subgroup of patients with reduced ejection fraction. Myocardial perfusion improvement could represent the underlying mechanism for the observed benefits.

One-year clinical outcome of biodegradable polymer sirolimus-eluting stent in diabetic patients: Insight from the ULISSE registry (ULtimaster Italian multicenter all comerS Stent rEgistry).

BACKGROUND: The ULISSE registry evaluated the real-world performance of the Ultimaster® biodegradable polymer sirolimus-eluting stent (BP-SES) in a multicenter-independent cohort of patients undergoing percutaneous coronary intervention, including a large proportion of diabetes mellitus (DM) patients. METHODS: In this subgroup analysis, 1,660 consecutive patients, 2,422 lesions, treated with BP-SES enrolled in the ULISSE registry were divided in two groups: DM (485 patients, 728 lesions) and non-DM (1,175 patients, 1,694 lesions). Primary endpoint was target lesion failure (TLF), a composite endpoint of cardiac-death, target-vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR) at 1-year. Secondary endpoint was TLR at 1-year. RESULTS: At 1-year follow-up TLF occurred in 5% overall patients and was significantly higher in DM patients (8 vs. 3.7%; p = .001), due to more cardiac deaths (3.4 vs. 1.1%; p = .002). TLR occurred in 3.2% overall patients, and it was not significantly higher in DM compared to non-DM patients (4.4 vs. 2.8%; p = .114). The incidence of stent thrombosis was low and similar between groups (0.4 vs. 0.9%; p = .526). Insulin-treated DM (ITDM) patients showed higher rate of TLF as compared to non-ITDM patients (13 vs. 6.5%; p = .041), but similar rate of TLR (6 vs. 4%; p = .405). After adjustment for relevant comorbidities, DM was not significantly associated with TLF or cardiac death in patients undergoing BP-SES implantation. CONCLUSIONS: This study is the first all-comers evaluation of BP-SES in DM patients. Our findings show that DM patients, mostly those with ITDM, still represent a vulnerable population and experience significantly higher rate of TLF. Overall BP-SES efficacy is considerable, although not statistically significant higher rate of TLR is still present in DM compared to non-DM patients.

Impella as Bridge to Durable Left Ventricular Assist Device in Acute Myocardial Infarction Cardiogenic Shock Patients.

Implantation of durable left ventricular assist device (LVAD) in cardiogenic shock (CS) patients after acute myocardial infarction (AMI) poses specific challenges (small left ventricular size, acute infarct area, need for antithrombotic therapy, status Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 1 with impaired organ function and derangements in coagulation and inflammatory parameters) which may affect outcomes. We reviewed data of all AMI-CS patients who were implanted LVAD after Impella support at a referral center with the aim to analyze feasibility, timing, and outcomes of durable LVAD implantation after tMCS with Impella due to AMI-CS. Twenty-one patients were treated between 2013 and 2023: all were in Society for Cardiovascular Angiography & Interventions (SCAI) class D-E and INTERMACS 1-2 at presentation, median LV ejection fraction (EF) and LV end-diastolic diameter (EDD) were 15 (10-20)% and 57 (54-60) mm, respectively. Eleven patients (52%) were supported with Impella CP, seven with Impella 5.0 (33%), and three (14%) with Impella 2.5. Axillary cannulation was performed in nine patients (43%). Five patients (24%) had concomitant venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Median duration of Impella support was 12 (8-14) days. Overall, the use of Impella was characterized by low rate of complications and allowed successful bridge to durable LVAD in all patients, with 100% 30 day survival rate.

Cat Scratch Endocarditis.

We reported a case of blood culture-negative infective endocarditis on a native valve, where the clinical presentation was exclusively related to extensive cerebral ischemia secondary to multiple systemic septic cardioembolic events. The cause was ascribed to subacute Bartonella henselae infection, presumably transmitted by cat scratch, documented by positive serologic findings.

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.

Pulmonary artery elastance as a predictor of hospital mortality in heart failure cardiogenic shock.

AIMS: The initial bundle of cares strongly affects haemodynamics and outcomes in acute decompensated heart failure cardiogenic shock (ADHF-CS). We sought to characterize whether 24 h haemodynamic profiling provides superior prognostic information as compared with admission assessment and which haemodynamic parameters best predict in-hospital death. METHODS AND RESULTS: All patients with ADHF-CS and with available admission and 24 h invasive haemodynamic assessment from two academic institutions were considered for this study. The primary endpoint was in-hospital death. Regression analyses were run to identify relevant predictors of study outcome. We included 127 ADHF-CS patients [65 (inter-quartile range 52-72) years, 25.2% female]. Overall, in-hospital mortality occurred in 26.8%. Non-survivors were older, with greater CS severity. Among admission variables, age [odds ratio (OR) = 1.06; 95% confidence interval (CI): 1.02-1.11; Padj = 0.005] and CPIRAP (OR = 0.62 for 0.1 increment; 95% CI: 0.39-0.95; Padj = 0.034) were found significantly associated with in-hospital death. Among 24 h haemodynamic univariate predictors of in-hospital death, pulmonary elastance (PaE) was the strongest (area under the curve of 0.77; 95% CI: 0.68-0.86). PaE (OR = 5.98; 95% CI: 2.29-17.48; Padj < 0.001), pulmonary artery pulsatility index (PAPi, OR = 0.77; 95% CI: 0.62-0.92; Padj = 0.013) and age (OR = 1.06; 95% CI: 1.02-1.11; Padj = 0.010) were independently associated with in-hospital death. Best cut-off for PaE was 0.85 mmHg/mL and for PAPi was 2.95; cohort phenotyping based on these PaE and PAPi thresholds further increased in-hospital death risk stratification; patients with 24 h high PaE and low PAPi exhibited the highest in-hospital mortality (56.2%). CONCLUSIONS: Pulmonary artery elastance has been found to be the most powerful 24 h haemodynamic predictor of in-hospital death in patients with ADHF-CS. Age, 24 h PaE, and PAPi are independently associated with hospital mortality. PaE captures right ventriclar (RV) afterload mismatch and PAPi provides a metric of RV adaptation, thus their combination generates four distinct haemodynamic phenotypes, enhancing in-hospital death risk stratification.

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.

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.

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.

Mixed Shock Complicating Cardiogenic Shock: Frequency, Predictors, and Clinical Outcomes.

BACKGROUND: Patients presenting with cardiogenic shock (CS) are at risk of developing mixed shock (MS), characterized by distributive-inflammatory phenotype. However, no objective definition exists for this clinical entity. METHODS: We assessed the frequency, predictors, and prognostic relevance of MS complicating CS, based on a newly proposed objective definition. MS complicating CS was defined as an objective shock state secondary to both an ongoing cardiogenic cause and a distributive-inflammatory phenotype arising at least 12 hours after the initial CS diagnosis, as substantiated by predefined longitudinal changes in hemodynamics, clinical, and laboratory parameters. RESULTS: Among 213 consecutive patients admitted at 2 cardiac intensive care units with CS, 13 with inflammatory-distributive features at initial presentation were excluded, leading to a cohort of 200 patients hospitalized with pure CS (67±13 years, 96% Society of Cardiovascular Angiography and Interventions CS stage class C or higher). MS complicating CS occurred in 24.5% after 120 (29-216) hours from CS diagnosis. Lower systolic arterial pressure (P=0.043), hepatic injury (P=0.049), and suspected/definite infection (P=0.013) at CS diagnosis were independent predictors of MS development. In-hospital mortality (53.1% versus 27.8%; P=0.002) and hospital stay (21 [13-48] versus 17 [9-27] days; P=0.018) were higher in the MS cohort. At logistic multivariable analysis, MS diagnosis (odds ratio [OR], 3.00 [95% CI, 1.39-6.63]; Padj=0.006), age (OR, 1.06 [95% CI, 1.03-1.10] years; Padj<0.001), admission systolic arterial pressure <100 mm Hg (OR, 2.41 [95% CI, 1.19-4.98]; Padj=0.016), and admission serum creatinine (OR, 1.61 [95% CI, 1.19-2.26]; Padj=0.003) conferred higher odds of in-hospital death, while early temporary mechanical circulatory support was associated with lower in-hospital death (OR, 0.36 [95% CI, 0.17-0.75]; Padj=0.008). CONCLUSIONS: MS complicating CS, objectively defined leveraging on longitudinal changes in distributive and inflammatory features, occurs in one-fourth of patients with CS, is predicted by markers of CS severity and inflammation at CS diagnosis, and portends higher hospital mortality.

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.