Revascularization and outcomes in ischaemic left ventricular dysfunction after heart failure admission: The RevascHeart study.

AIMS: Despite numerous trials on revascularization in patients with heart failure (HF) and ischaemic left ventricular (LV) dysfunction, its role remains unsettled. Guideline-directed medical therapy (GDMT) for HF has shown benefits on outcomes. This multicentre study aims to compare long-term mortality between revascularization and GDMT in patients with ischaemic LV dysfunction following admission for HF. METHODS AND RESULTS: Between 2012 and 2023, 408 patients admitted for HF with a LV ejection fraction (LVEF) of 40% or less and documented coronary artery disease (CAD) were included. Patients were categorized into two groups based on their initial treatment decision: revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) or GDMT. The primary outcome was rate of all-cause or cardiovascular mortality, and secondary outcomes included type of revascularization (PCI vs. CABG) and LV reverse remodelling. After a median 44.6-month follow-up, 100 patients (33%) died in the revascularization group, compared to 44 (43%) in the GDMT group. Multivariate analysis showed no significant benefit of revascularization on all-cause mortality (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.48-1.39, p = 0.45) or cardiovascular mortality (HR 0.97, 95% CI 0.62-1.52, p = 0.90) compared to GDMT. Neither CABG (HR 0.74, 95% CI 0.51-1.08, p = 0.13) nor PCI (HR 0.98, 95% CI 0.62-1.55, p = 0.93) demonstrated a mortality reduction compared to GDMT. Both groups experienced significant reductions in LV size and improvements in LVEF, greater in the revascularization group. CONCLUSION: Revascularization did not outperform GDMT in ischaemic LV dysfunction following HF admission in this retrospective analysis. Larger prospective studies are needed to clarify the potential role of revascularization in improving outcomes.

Prediction of left ventricular thrombus after myocardial infarction: a cardiac magnetic resonance-based prospective registry.

BACKGROUND: Left ventricular thrombus (LVTh) is a severe complication after ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: We aim to predict LVTh occurrence by cardiac magnetic resonance (CMR) using clinical, echocardiographic, and electrocardiographic (ECG) variables readily available at admission. METHODS: We included 590 reperfused STEMI patients who underwent early (1-week) and/or late (6-month) CMR in our institution. Baseline clinical, echocardiographic (left ventricular ejection fraction -LVEF-) and ECG data (summatory of ST-segment elevation -sum-STE- and Q-wave and residual ST-elevation >1 mm -Q-STE-) during admission were registered. Multivariate binary logistic regression models and receiver operating characteristic curves were computed for LVTh prediction. RESULTS: LVTh was detected by CMR in 43 (7.3 %) patients and was predicted by previous chronic coronary syndrome (CCS, HR 4.74 [1.82-12.35], p = 0.001), anterior STEMI (HR 10.93 [2.47-48.31], p = 0.002), LVEF (HR 0.96 [0.93-0.99] per %, p = 0.008), maximum sum-STE (HR 1.04 [1.01-1.07] per mm, p = 0.04), and Q-STE (HR 1.31 [1.08-1.6] per lead, p = 0.008). High-risk patients with both major (anterior STEMI and Q-STE in ≥1 leads) and 1-3 minor (CCS, maximum sum-STE >10 mm, LVEF <50%) factors showed the highest LVTh risk (19.6 % within 6 months). The model showed excellent discrimination ability (area under the curve=0.85 [0.81-0.9], p < 0.001). Simplified 4-variable (excluding sum-STE) and 3-variable (also excluding CCS) risk scores showed similar discrimination ability and were externally validated. CONCLUSIONS: LVTh within 6 months post-STEMI can be predicted using pre-discharge clinical (anterior infarction and CCS), echocardiographic (LVEF), and ECG (sum-STE and Q-STE) data. Our results can help select patients who should undergo CMR after STEMI for LVTh detection.

Prognostic role of persistent angina after percutaneous revascularization in chronic coronary syndrome with altered angiography and stress CMR.

INTRODUCTION AND OBJECTIVES: In patients with established chronic coronary syndrome (CCS), the significance of persistent angina is controversial. We aimed to evaluate the prognostic role of persistent angina in symptomatic CCS patients with abnormal stress cardiovascular magnetic resonance (CMR) and altered angiographic findings undergoing percutaneous revascularization. METHODS: We analyzed 334 CCS patients with Canadian Cardiovascular Society angina class ≥ 2, perfusion deficits on stress CMR and severe lesions in angiography who underwent medical therapy optimization plus CMR-guided percutaneous revascularization. We investigated the association of persistent angina at 6 months postintervention with subsequent cardiac death, myocardial infarction, and hospital admission. RESULTS: All patients had angina class ≥ 2 (mean: 2.8 ± 0.7), abnormal stress CMR (mean ischemic burden: 5.8 ± 2.7 segments), and severe angiographic lesions. The angina resolution rates were 81% at 6 months, and 81%, 81%, and 77% at 1, 2, and 5 years, respectively. During a median follow-up of 8.9 years, persistent angina was independently associated with higher rates of subsequent cardiac death (13% vs 4%; HR, 3.7; 95%CI, 1.5-9.2; P = .005), myocardial infarction (24% vs 6%; HR, 4.9; 95%CI, 2.4-9.9; P < .001), and hospital admission for heart failure (27% vs 13%; HR, 2.7; 95%CI, 1.5-5.2; P = .001). CONCLUSIONS: In CCS patients with robust diagnostic evidence from symptoms, stress CMR, and angiography, persistent angina after percutaneous revascularization is a strong predictor of subsequent cardiac death, myocardial infarction, and hospital admission for heart failure.

Hospitalization of Symptomatic Patients With Heart Failure and Moderate to Severe Functional Mitral Regurgitation Treated With MitraClip: Insights From RESHAPE-HF2.

BACKGROUND: For patients with functional mitral regurgitation (FMR) and symptomatic heart failure (HF), randomized trials of mitral transcatheter edge-to-edge repair (M-TEER) have produced conflicting results. OBJECTIVES: This study sought to assess the impact of M-TEER on hospitalization rates, and explore the effects of M-TEER on patients who did or did not have a history of recent HF hospitalizations before undergoing M-TEER. METHODS: RESHAPE-HF2 (Randomized Investigation of the MitraClip Device in Heart Failure: 2nd Trial in Patients with Clinically Significant Functional Mitral Regurgitation) included patients with symptomatic HF and moderate to severe FMR (mean effective regurgitant orifice area 0.25 cm2; 14% >0.40 cm2, 23% <0.20 cm2) and showed that M-TEER reduced recurrent HF hospitalizations with and without the addition of cardiovascular (CV) death and improved quality of life. We now report the results of prespecified analyses on hospitalization rates and for the subgroup of patients (n = 333) with a HF hospitalization in the 12 months before randomization. RESULTS: At 24 months, the time to first event of CV death or HF hospitalization (HR: 0.65; 95% CI: 0.49-0.85; P = 0.002), the rate of recurrent CV hospitalizations (rate ratio [RR]: 0.75; 95% CI: 0.57-0.99; P = 0.046), the composite rate of recurrent CV hospitalizations and all-cause mortality (RR: 0.74; 95% CI: 0.57-0.95; P = 0.017), and of recurrent CV death and CV hospitalizations (RR: 0.76; 95% CI: 0.58-0.99; P = 0.040), were all lower in the M-TEER group. The RR of recurrent hospitalizations for any cause was 0.82 (95% CI: 0.63-1.07; P = 0.15) for patients in the M-TEER group vs control group patients. Patients randomized to M-TEER lost fewer days due to death or HF hospitalization (13.9% [95% CI: 13.0%-14.8%] vs 17.4% [95% CI: 16.4%-18.4%] of follow-up time; P < 0.0001, and 1,067 vs 1,776 total days lost; P < 0.0001). Patients randomized to M-TEER also had better NYHA functional class at 30 days and at 6, 12, and 24 months of follow-up (P < 0.0001). A history of HF hospitalizations before randomization was associated with worse outcomes and greater benefit with M-TEER on the rate of the composite of recurrent HF hospitalizations and CV death (Pinteraction = 0.03) and of recurrent HF hospitalizations within 24 months (Pinteraction = 0.06). CONCLUSIONS: These results indicate that a broader application of M-TEER in addition to optimal guideline-directed medical therapy should be considered among patients with symptomatic HF and moderate to severe FMR, particularly in those with a history of a recent hospitalization for HF.

Patiromer Facilitates Angiotensin Inhibitor and Mineralocorticoid Antagonist Therapies in Patients With Heart Failure and Hyperkalemia.

BACKGROUND: Hyperkalemia (HK) is associated with suboptimal renin-angiotensin system (RAS) inhibitor and mineralocorticoid receptor antagonist (MRA) use in heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: This study sought to assess characteristics and RAS inhibitor/MRA use in patients receiving patiromer during the DIAMOND (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) run-in phase. METHODS: Patients with HFrEF and HK or past HK entered a run-in phase of ≤12 weeks with patiromer-facilitated RAS inhibitor/MRA optimization to achieve ≥50% recommended RAS inhibitor dose, 50 mg/d MRA, and normokalemia. Patients achieving these criteria (randomized group) were compared with the run-in failure group (patients not meeting the randomization criteria). RESULTS: Of 1,038 patients completing the run-in, 878 (84.6%) were randomized and 160 (15.4%) were run-in failures. Overall, 422 (40.7%) had HK entering run-in with a similar frequency in the randomized and run-in failure groups (40.3% vs 42.5%; P = 0.605). From start to the end of run-in, in the randomized group, an increase was observed in target RAS inhibitor and MRA use in patients with HK (RAS inhibitor: 76.8% to 98.6%; MRA: 35.9% to 98.6%) and past HK (RAS inhibitor: 60.5% to 98.1%; MRA: 15.6% to 98.7%). Despite not meeting the randomization criteria, an increase after run-in was observed in the run-in failure group in target RAS inhibitor (52.5% to 70.6%) and MRA use (15.0% to 48.1%). This increase was observed in patients with HK (RAS inhibitor: 51.5% to 64.7%; MRA: 19.1% to 39.7%) and past HK (RAS inhibitor: 53.3% to 75.0%; MRA: 12.0% to 54.3%). CONCLUSIONS: In patients with HFrEF and HK or past HK receiving suboptimal RAS inhibitor/MRA therapy, RAS inhibitor/MRA optimization increased during patiromer-facilitated run-in.

Patiromer for Heart Failure Medication Optimization in Patients With Current or Past Hyperkalemia: DIAMOND Subanalysis.

BACKGROUND: For heart failure with reduced ejection fraction (HFrEF), suboptimal use of renin-angiotensin-aldosterone system inhibitors (RAASis), including mineralocorticoid receptor antagonists (MRAs), due to hyperkalemia, may be improved by potassium binders. OBJECTIVES: This prespecified analysis of the phase 3 DIAMOND (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) trial assessed the effect of patiromer in patients with HFrEF and either current or past hyperkalemia. METHODS: Patients with HFrEF and current or past (within 1 year before enrollment) hyperkalemia (serum potassium [sK+] >5.0 mmol/L) entered a single-blind, run-in phase to optimize RAASis while receiving patiromer. They were subsequently randomized, double-blind, to continue patiromer or change to placebo. RESULTS: Of the 1,038 patients who completed run-in, 354 (83.9%) of 422 with current hyperkalemia and 524 (85.1%) of 616 with past hyperkalemia achieved RAASi optimization and were randomized to treatment. During the double-blind phase, patiromer lowered sK+ levels compared with placebo in both the current and past hyperkalemia subgroups: difference in adjusted mean change from baseline: -0.12 (95% CI: -0.17 to -0.07) and -0.08 (95% CI: -0.12 to -0.05), respectively; Pinteraction = 0.166. Patiromer was more effective than placebo in maintaining MRA at target dose in patients with current vs past hyperkalemia (HR: 0.45 [95% CI: 0.26-0.76] vs HR: 0.85 [95% CI: 0.54-1.32]; Pinteraction = 0.031). Adverse events were similar between subgroups. CONCLUSIONS: The use of patiromer facilitates achieving target doses of RAASis in patients with HFrEF with either current or past hyperkalemia. For those with current hyperkalemia before RAASi optimization, use of patiromer may be more beneficial in helping to maintain sK+ control and achieve MRA target dose. (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure [DIAMOND]; NCT03888066).

Interatrial Shunt Treatment for Heart Failure: The Randomized RELIEVE-HF Trial.

BACKGROUND: An interatrial shunt may provide an autoregulatory mechanism to decrease left atrial pressure and improve heart failure (HF) symptoms and prognosis. METHODS: Patients with symptomatic HF with any left ventricular ejection fraction (LVEF) were randomized 1:1 to transcatheter shunt implantation versus a placebo procedure, stratified by reduced (≤40%) versus preserved (>40%) LVEF. The primary safety outcome was a composite of device-related or procedure-related major adverse cardiovascular or neurological events at 30 days compared with a prespecified performance goal of 11%. The primary effectiveness outcome was the hierarchical composite ranking of all-cause death, cardiac transplantation or left ventricular assist device implantation, HF hospitalization, outpatient worsening HF events, and change in quality of life from baseline measured by the Kansas City Cardiomyopathy Questionnaire overall summary score through maximum 2-year follow-up, assessed when the last enrolled patient reached 1-year follow-up, expressed as the win ratio. Prespecified hypothesis-generating analyses were performed on patients with reduced and preserved LVEF. RESULTS: Between October 24, 2018, and October 19, 2022, 508 patients were randomized at 94 sites in 11 countries to interatrial shunt treatment (n=250) or a placebo procedure (n=258). Median (25th and 75th percentiles) age was 73.0 years (66.0, 79.0), and 189 patients (37.2%) were women. Median LVEF was reduced (≤40%) in 206 patients (40.6%) and preserved (>40%) in 302 patients (59.4%). No primary safety events occurred after shunt implantation (upper 97.5% confidence limit, 1.5%; P<0.0001). There was no difference in the 2-year primary effectiveness outcome between the shunt and placebo procedure groups (win ratio, 0.86 [95% CI, 0.61-1.22]; P=0.20). However, patients with reduced LVEF had fewer adverse cardiovascular events with shunt treatment versus placebo (annualized rate 49.0% versus 88.6%; relative risk, 0.55 [95% CI, 0.42-0.73]; P<0.0001), whereas patients with preserved LVEF had more cardiovascular events with shunt treatment (annualized rate 60.2% versus 35.9%; relative risk, 1.68 [95% CI, 1.29-2.19]; P=0.0001; Pinteraction<0.0001). There were no between-group differences in change in Kansas City Cardiomyopathy Questionnaire overall summary score during follow-up in all patients or in those with reduced or preserved LVEF. CONCLUSIONS: Transcatheter interatrial shunt implantation was safe but did not improve outcomes in patients with HF. However, the results from a prespecified exploratory analysis in stratified randomized groups suggest that shunt implantation is beneficial in patients with reduced LVEF and harmful in patients with preserved LVEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03499236.

High-sensitivity C-reactive protein and risk of clinical outcomes in patients with acute heart failure.

Inflammation is relevant in the pathogenesis and progression of heart failure (HF). Previous studies have shown that elevated high-sensitivity C-reactive protein (hsCRP) are associated with greater severity and may be associated with adverse outcomes. In this study, we sought to evaluate the prognostic role of hsCRP in a non-selected cohort of patients with acute HF. We prospectively included a multicenter cohort of 3,395 patients following an admission for acute HF. HsCRP levels were evaluated during the first 24 h following admission. Study endpoints were the risks of all-cause mortality, CV-mortality, and total HF readmissions. The mean age was 74.2 ± 11.2 years and 1,826 (53.8%) showed a left ventricular ejection fraction (LVEF) ≥ 50%. Median hsCRP was 12.9 mg/L (5.4-30 mg/L). Over a median follow-up of 1.8 (0.6-4.1) years, 1,574 (46.4%) patients died, and 1,341 (39.5%) patients were readmitted for worsening HF. After multivariable adjustment, hsCRP values were significantly and positively associated with a higher risk of all-cause and CV mortality (p = 0.003 and p = 0.001, respectively), as well as a higher risk of recurrent HF admissions (p < 0.001). These results remained consistent across important subgroups, such as LVEF, sex, age, or renal function. In patients with acute HF, hsCRP levels were independently associated with an increased risk of long-term death and total HF readmissions.

Looking for the ideal medication for heart failure with reduced ejection fraction: a narrative review.

The main goals of the pharmacological treatment of Heart failure with reduced ejection fraction (HFrEF) are the reduction of mortality and the prevention of hospitalizations. However, other outcomes such as improvements in cardiac remodeling and clinical status, functional capacity and quality of life, should be taken into account. Also, given the significant inter-individual and intra-individual variability of HF, and the fact that patients usually present with comorbidities, an appropriate treatment for HFrEF should exert a clinical benefit in most patient profiles irrespective of their characteristics or the presence of comorbidities, while providing organ protection beyond the cardiovascular system. The aim of this narrative review is to determine which are the proven effects of the guideline-directed treatments for HFrEF on five key clinical outcomes: cardiovascular mortality and hospitalization due to HF, sudden death, reverse cardiac remodeling, renal protection and evidence in hospitalized patients. Publications that fulfilled the pre-established selection criteria were selected and reviewed. Renin-angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), sodium-glucose co-transporter 2 inhibitors (SGLT2i) show a benefit in terms of mortality and hospitalization rates. ARNI, BB, and MRA have demonstrated a significant positive effect on the incidence of sudden death. ARB, ARNI, BB and SGLT2i have been associated with clear benefits in reverse cardiac remodeling. Additionally, there is consistent evidence of renal protection from ARB, ARNI, and SGLT2i in renal protection and of benefits for hospitalized patients from ARNI and SGLT2i. In conclusion, the combination of drugs that gather most beneficial effects in HFrEF, beyond cardiovascular mortality and hospitalization, would be ideally pursued.

Translating the 2021 ESC heart failure guideline recommendations in daily practice: Results from a heart failure survey. A scientific statement of the ESC Council for Cardiology Practice and the Heart Failure Association of the ESC.

AIMS: Real-world data show that guidelines are insufficiently implemented, and particularly guideline-directed medical therapies (GDMT) are underused in patients with heart failure and reduced ejection fraction (HFrEF) in clinical practice. The Council for Cardiology Practice and the Heart Failure Association of the European Society of Cardiology (ESC) developed a survey aiming to (i) evaluate the perspectives of the cardiology community on the 2021 ESC heart failure (HF) guidelines, (ii) pinpoint disparities in disease management, and (iii) propose strategies to enhance adherence to HF guidelines. METHODS AND RESULTS: A 22-question survey regarding the diagnosis and treatment of HFrEF was delivered between March and June 2022. Of 457 physicians, 54% were general cardiologists, 19.4% were HF specialists, 18.9% other cardiac specialists, and 7.7% non-cardiac specialists. For diagnosis, 52.1% employed echocardiography and natriuretic peptides (NPs), 33.2% primarily used echocardiography, and 14.7% predominantly relied on NPs. The first drug class initiated in HFrEF was angiotensin-converting enzyme inhibitors/angiotensin receptor-neprilysin inhibitor (ACEi/ARNi) (91.2%), beta-blockers (BB) (73.8%), mineralocorticoid receptor antagonists (MRAs) (53.4%), and sodium-glucose cotransporter 2 (SGLT2) inhibitors (48.1%). The combination ACEi/ARNi + MRA+ BB was preferred by 39.3% of physicians, ACEi/ARNi + SGLT2 inhibitors + BB by 33.3%, and ACEi/ARNi + BB by 22.2%. The time required to initiate and optimize GDMT was estimated to be <1 month by 8.3%, 1-3 months by 52%, 3-6 months by 31.8%, and >6 months by 7.9%. Compared to general cardiologists, HF specialists/academic cardiologists reported lower estimated time-to-initiation, and more commonly preferred a parallel initiation of GDMT rather than a sequential approach. CONCLUSION: Participants generally followed diagnostic and treatment guidelines, but variations in HFrEF management across care settings or HF specialties were noted. The survey may raise awareness and promote standardized HF care.

Awareness, access, and adoption of natriuretic peptides for diagnosis of heart failure.

AIMS: This survey investigates natriuretic peptide (NP) testing in community and hospital settings, assessing awareness, accessibility, and utilization. METHODS AND RESULTS: This investigator-initiated survey, conceived within the HFA of the European Society of Cardiology, comprised 14 questions. It underwent validation and pilot testing to ensure question readability and online system functionality. The survey was accessible for 87 days, from 5 April 2023 to 1 July 2023 via a web platform. There were 751 healthcare professionals across 99 countries who responded. Of them, 92.5% had access to NPs testing in hospital whereas 34.3% had no access to NTproBNP in community settings. Access to point of care NP testing was uncommon (9.6%). Public insurance fully covered NPs testing in 31.0% of cases, with private insurance providing coverage in 37.9%. The majority (84.0%) of participants believed that the medical evidence supporting NPs testing was strong, and 54.7% considered it cost-effective. Also, 35.8% found access, awareness, and adoption to be in favour of NPs testing both in hospital and community settings. Strategies to optimize NP testing involved regular guideline updates (57.9%), prioritizing NPs testing for dyspnoea assessment (36.4%), and introducing clinician feedback mechanisms (21.2%). Notably, 40% lacked a community-based HF diagnostic pathway for referring high-NP patients for echocardiography and cardiology evaluation. CONCLUSIONS: This survey reveals NP awareness, access, and adoption across several countries. Highlighting the importance of community-based early heart failure diagnosis and optimizing HF diagnostic pathways remains a crucial, unmet opportunity to improve patient outcomes.

Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation.

BACKGROUND: Whether transcatheter mitral-valve repair improves outcomes in patients with heart failure and functional mitral regurgitation is uncertain. METHODS: We conducted a randomized, controlled trial involving patients with heart failure and moderate to severe functional mitral regurgitation from 30 sites in nine countries. The patients were assigned in a 1:1 ratio to either transcatheter mitral-valve repair and guideline-recommended medical therapy (device group) or medical therapy alone (control group). The three primary end points were the rate of the composite of first or recurrent hospitalization for heart failure or cardiovascular death during 24 months; the rate of first or recurrent hospitalization for heart failure during 24 months; and the change from baseline to 12 months in the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS; scores range from 0 to 100, with higher scores indicating better health status). RESULTS: A total of 505 patients underwent randomization: 250 were assigned to the device group and 255 to the control group. At 24 months, the rate of first or recurrent hospitalization for heart failure or cardiovascular death was 37.0 events per 100 patient-years in the device group and 58.9 events per 100 patient-years in the control group (rate ratio, 0.64; 95% confidence interval [CI], 0.48 to 0.85; P = 0.002). The rate of first or recurrent hospitalization for heart failure was 26.9 events per 100 patient-years in the device group and 46.6 events per 100 patient-years in the control group (rate ratio, 0.59; 95% CI, 0.42 to 0.82; P = 0.002). The KCCQ-OS score increased by a mean (±SD) of 21.6±26.9 points in the device group and 8.0±24.5 points in the control group (mean difference, 10.9 points; 95% CI, 6.8 to 15.0; P<0.001). Device-specific safety events occurred in 4 patients (1.6%). CONCLUSIONS: Among patients with heart failure with moderate to severe functional mitral regurgitation who received medical therapy, the addition of transcatheter mitral-valve repair led to a lower rate of first or recurrent hospitalization for heart failure or cardiovascular death and a lower rate of first or recurrent hospitalization for heart failure at 24 months and better health status at 12 months than medical therapy alone. (Funded by Abbott Laboratories; RESHAPE-HF2 ClinicalTrials.gov number, NCT02444338.).

Circulating biomarkers of myocardial remodelling: current developments and clinical applications.

Myocardial remodelling, entailing cellular and molecular changes in the different components of the cardiac tissue in response to damage, underlies the morphological and structural changes leading to cardiac remodelling, which in turn contributes to cardiac dysfunction and disease progression. Since cardiac tissue is not available for histomolecular diagnosis, surrogate markers are needed for evaluating myocardial remodelling as part of the clinical management of patients with cardiac disease. In this setting, circulating biomarkers, a component of the liquid biopsy, provide a promising approach for the fast, affordable and scalable screening of large numbers of patients, allowing the detection of different pathological features related to myocardial remodelling, aiding in risk stratification and therapy monitoring. However, despite the advances in the field and the identification of numerous potential candidates, their implementation in clinical practice beyond natriuretic peptides and troponins is mostly lacking. In this review, we will discuss some biomarkers related to alterations in the main cardiac tissue compartments (cardiomyocytes, extracellular matrix, endothelium and immune cells) which have shown potential for the assessment of cardiovascular risk, cardiac remodelling and therapy effects. The hurdles and challenges for their translation into clinical practice will also be addressed.

Patiromer-Facilitated Renin-Angiotensin-Aldosterone System Inhibitor Utilization in Patients with Heart Failure with or without Comorbid Chronic Kidney Disease: Subgroup Analysis of DIAMOND Randomized Trial.

INTRODUCTION: Renin-angiotensin-aldosterone system inhibitor (RAASi; including mineralocorticoid receptor antagonists [MRAs]) benefits are greatest in patients with heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD); however, the risk of hyperkalemia (HK) is high. METHODS: The DIAMOND trial (NCT03888066) assessed the ability of patiromer to control serum potassium (sK+) in patients with HFrEF with/without CKD. Prior to randomization (double-blind withdrawal, 1:1), patients on patiromer had to achieve ≥50% recommended doses of RAASi and 50 mg/day of MRA with normokalemia during a run-in period. The present analysis assessed the effect of baseline estimated glomerular filtration rate (eGFR) in subgroups of ≥/<60, ≥/<45 (prespecified), and ≥/<30 mL/min/1.73 m2 (added post hoc). RESULTS: In total, 81.3, 78.9, and 81.1% of patients with eGFR <60, <45, and <30 mL/min/1.73 m2 at screening achieved RAASi/MRA targets. A greater efficacy of patiromer versus placebo to control sK+ in patients with more advanced CKD was reported (p-interaction ≤ 0.027 for all eGFR subgroups). Greater effects on secondary endpoints were observed with patiromer versus placebo in patients with eGFR <60 and <45 mL/min/1.73 m2. Adverse effects were similar between patiromer and placebo across subgroups. CONCLUSION: Patiromer enabled use of RAASi, controlled sK+, and minimized HK risk in patients with HFrEF, with greater effect sizes for most endpoints noted in patient subgroups with lower eGFR. Patiromer was well tolerated by patients in all eGFR subgroups.

Lower heart rate in patients with acute heart failure: the role of left ventricular ejection fraction.

BACKGROUND: The clinical impact of heart rate (HR) in heart failure with preserved ejection fraction (HFpEF) is a matter of debate. Among those with HFpEF, chronotropic incompetence (CI) has emerged as a pathophysiological mechanism linked to the severity of the disease. In this study, we sought to evaluate whether admission heart rate in acute heart failure differs along left ventricular ejection fraction (LVEF). METHODS: We included retrospectively 3,712 consecutive patients admitted for acute heart failure (AHF) in the Cardiology department of a third level center. HR values were assessed at presentation. LVEF was assessed by transthoracic echocardiogram during the index admission and stratified into four categories: reduced ejection fraction (≤40%), mildly reduced ejection fraction (41-49%), preserved ejection fraction (50-64%) and supranormal ejection fraction (≥65%). The association between HR and LVEF was assessed by multivariate linear and multinomial regression analyses. RESULTS: The mean age of the sample was 73,9 ± 11.3 years, 1,734 (47,4%) were women, and 1,214 (33,2%), 570 (15,6%), 1,229 (33,6%) and 648 (17,7%) patients showed LVEF ≤40%, 41-49%, 50-64%, and ≥65% respectively. The median HR at admission was 95 (IQR 78-120) beats per minute and 1,653 were on atrial fibrillation (45.2%). There was an inverse relationship between HR at admission and LVEF. Lower HR was significantly associated with a higher LVEF in the whole sample (p < 0,001). This inverse relationship was found in sinus rhythm but not in patients with atrial fibrillation. CONCLUSION: HR at admission for AHF is a predictor of LVEF but only in patients with sinus rhythm.

Biomarkers of lung congestion and injury in acute heart failure.

Acute heart failure (AHF) classification and management are primarily based on lung congestion and/or hypoperfusion. The quantification of the vascular and tissue lung damage is not standard practice though biomarkers of lung injury may play a relevant role in this context. Haemodynamic stress promotes alveolar and vascular derangement with loss of functional units, impaired lung capillary permeability and fluid swelling. This culminates in a remodelling process with activation of inflammatory and cytokines pathways. Four families of lung surfactant proteins (i.e., SP-A, SP-B, SP-C, and SP-D), essential for the membrane biology and integrity are released by alveolar type II pneumocites. With deregulation of fluid handling and gas exchange pathways, SPs become sensitive markers of lung injury. We report the pathobiology of lung damage; the pathophysiological and clinical implications of alveolar SPs along with the newest evidence for some classical HF biomarkers that have also shown to reflect a vascular and/or a tissue lung-related activity.