Diagnosis of heart failure with preserved ejection fraction: a systematic narrative review of the evidence.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a common condition in clinical practice, affecting more than half of patients with HF. HFpEF is associated with morbidity and mortality and with considerable healthcare resource utilization and costs. Therefore, early diagnosis is crucial to facilitate prompt management, particularly initiation of sodium-glucose co-transporter 2 inhibitors. Although European guidelines define HFpEF as the presence of symptoms with or without signs of HF, left ventricular EF ≥ 50%, and objective evidence of cardiac structural and/or functional abnormalities, together with elevated natriuretic peptide levels, the diagnosis of HFpEF remains challenging. First, there is no clear consensus on how HFpEF should be defined. Furthermore, diagnostic tools, such as natriuretic peptide levels and resting echocardiogram findings, are significantly limited in the diagnosis of HFpEF. As a result, some patients are overdiagnosed (i.e., elderly people with comorbidities that mimic HF), although in other cases, HFpEF is overlooked. In this manuscript, we perform a systematic narrative review of the diagnostic approach to patients with HFpEF. We also propose a comprehensible algorithm that can be easily applied in daily clinical practice and could prove useful for confirming or ruling out a diagnosis of HFpEF.

Combinational Diuretics in Heart Failure.

PURPOSE OF REVIEW: Diuretics are the cornerstone therapy for acute heart failure (HF) and congestion. Patients chronically exposed to loop diuretics may develop diuretic resistance as a consequence of nephron remodelling, and the combination of diuretics will be necessary to improve diuretic response and achieve decongestion. This review integrates data from recent research and offers a practical approach to current pharmacologic therapies to manage congestion in HF with a focus on combinational therapy. RECENT FINDINGS: Until recently, combined diuretic treatment was based on observational studies and expert opinion. Recent evidence from clinical trials has shown that combined diuretic treatment can be started earlier without escalating the doses of loop diuretics with an adequate safety profile. Diuretic combination is a promising strategy for overcoming diuretic resistance in HF. Further studies aiming to get more insights into the pathophysiology of diuretic resistance and large clinical trials confirming the safety and efficacy over standard diuretics regimens are warranted.

Sex differences in Cardiorenal Syndrome: Insights from CARDIOREN Registry.

PURPOSE OF THE WORK: Although sex-specific differences in heart failure (HF) or kidney disease (KD) have been analyzed separately, the predominant cardiorenal phenotype by sex has not been described. This study aims to explore the sex-related differences in cardiorenal syndrome (CRS) in a contemporary cohort of outpatients with HF. FINDINGS: An analysis of the Cardiorenal Spanish registry (CARDIOREN) was performed. CARDIOREN Registry is a prospective multicenter observational registry including 1107 chronic ambulatory HF patients (37% females) from 13 Spanish HF clinics. Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2 was present in 59.1% of the overall HF population, being this prevalence higher in the female population (63.2% vs. 56.6%, p = 0.032, median age: 81 years old, IQR:74-86). Among those with kidney dysfunction, women displayed higher odds of showing HF with preserved ejection fraction (HFpEF) (odds ratio [OR] = 4.07; confidence interval [CI] 95%: 2.65-6.25, p < 0.001), prior valvular heart disease (OR = 1.76; CI 95%:1.13-2.75, p = 0.014), anemia (OR: 2.02; CI 95%:1.30-3.14, p = 0.002), more advanced kidney disease (OR for CKD stage 3: 1.81; CI 95%:1.04-3.13, p = 0.034; OR for CKD stage 4: 2.49, CI 95%:1.31-4.70, p = 0.004) and clinical features of congestion (OR:1.51; CI 95%: 1.02-2.25, p = 0.039). On the contrary, males with cardiorenal disease showed higher odds of presenting HF with reduced ejection fraction (HFrEF) (OR:3.13; CI 95%: 1.90-5.16, p < 0.005), ischemic cardiomyopathy (OR:2.17; CI 95%: 1.31-3.61, p = 0.003), hypertension (OR = 2.11; CI 95%:1.18-3.78, p = 0.009), atrial fibrillation (OR:1.71; CI 95%: 1.06-2.75, p = 0.025), and hyperkalemia (OR:2.43, CI 95%: 1.31-4.50, p = 0.005). In this contemporary registry of chronic ambulatory HF patients, we observed sex-related differences in patients with combined heart and kidney disease. The emerging cardiorenal phenotype characterized by advanced CKD, congestion, and HFpEF was predominantly observed in women, whereas HFrEF, ischemic etiology, hypertension, hyperkalemia, and atrial fibrillation were more frequently observed in men.

Do Women Physicians Accept and Follow Heart Failure Guidelines More Than Men?

PURPOSE OF REVIEW: Our aim was to assess the degree of acceptance of the European Clinical Practice Guidelines (CPG) on heart failure (HF) among Spanish physicians according to sex. This was a cross-sectional study, employing Google Forms, conducted by a group of HF experts from the Region of Madrid (Spain), between November 2021 and February 2022, among specialists and residents of Cardiology, Internal Medicine, and Primary Care from Spain. RECENT FINDINGS: A total of 387 physicians-173 women (44.7%)-from 128 different centers completed the survey. Compared to men, women were significantly younger (38.2 ± 9.1 years vs. 40.6 ± 11.2 years; p = 0.024) and had fewer years of clinical practice (12.1 ± 8.1 years vs. 14.5 ± 10.7 years; p = 0.014). Briefly, women and men had a positive opinion of the guidelines and thought that implementing quadruple therapy is feasible in less than 8 weeks. Women followed more frequently than men the new paradigm of "4 pillars at lowest doses" and considered more frequently the establishment of quadruple therapy before implanting a cardiac device. Although they agreed about "low blood pressure" as the major limitation for achieving quadruple therapy in heart failure with reduced ejection fraction, there were discrepancies on the second most frequent barrier, and women were more proactive when initiating SGLT2 inhibitors. In a large survey including nearly 400 doctors from all over Spain to provide real-world opinion on 2021 ESC HF Guidelines and experience with SGLT2 inhibitors, women follow more frequently the new paradigm of "4 pillars at lowest doses", consider more frequently the establishment of quadruple therapy before implanting a cardiac device, and were more proactive when initiating SGLT2 inhibitors. Further studies confirming an association of sex with a better compliance of HF guidelines are needed.

Usefulness of Serial Multiorgan Point-of-Care Ultrasound in Acute Heart Failure: Results from a Prospective Observational Cohort.

Background and Objectives: Acute heart failure (AHF) is a common disease and a cause of high morbidity and mortality, constituting a major health problem. The main purpose of this study was to determine the impact of multiorgan ultrasound in identifying pulmonary hypertension (PH), a major prognostic factor in patients admitted due to AHF, and assess whether there are significant changes in the venous excess ultrasonography (VE × US) score or femoral vein Doppler at discharge. Materials and Methods: Patients were evaluated with a standard protocol of lung ultrasound, echocardiography, inferior vena cava (IVC) and hepatic, portal, intra-renal and femoral vein Doppler flow patterns at admission and on the day of discharge. Results: Thirty patients were enrolled during November 2021. The mean age was seventy-nine years (Standard Deviation-SD 13.4). Seven patients (23.3%) had a worsening renal function during hospitalization. Regarding ultrasound findings, VE × US score was calculated at admission and at discharge, unexpectedly remaining unchanged or even worsened (21 patients, 70.0%). The area under the curve for the lung score was 83.9% (p = 0.008), obtaining a cutoff value of 10 that showed a sensitivity of 82.6% and a specificity of 71.4% in the identification of intermediate and high PH. It was possible to monitor significant changes between both exams on the lung score (16.5 vs. 9.3; p < 0.001), improvement in the hepatic vein Doppler pattern (2.4 vs. 2.1; p = 0.002), improvement in portal vein Doppler pattern (1.7 vs. 1.4; p = 0.023), without significant changes in the intra-renal vein Doppler pattern (1.70 vs. 1.57; p = 0.293), VE × US score (1.3 vs. 1.1; p = 0.501), femoral vein Doppler pattern (2.4 vs. 2.1; p = 0.161) and IVC collapsibility (2.0 vs. 2.1; p = 0.420). Conclusions: Our study results suggest that performing serial multiorgan Point-of-Care ultrasound can help us to better identify high and intermediate probability of PH patients with AHF. Currently proposed multi-organ, venous Doppler scanning protocols, such as the VE × US score, should be further studied before expanding its use in AHF patients.

Clinical characteristics of wild-type transthyretin cardiac amyloidosis: disproving myths.

AIMS: Wild-type transthyretin amyloidosis (ATTRwt) is mostly considered a disease predominantly of elderly male, characterized by concentric LV hypertrophy, preserved LVEF, and low QRS voltages. We sought to describe the characteristics of a large cohort of ATTRwt patients to better define the disease. METHODS AND RESULTS: Clinical findings of consecutive ATTRwt patients diagnosed at 2 centres were reviewed. ATTRwt was diagnosed histologically or non-invasively (LV hypertrophy ≥12 mm, intense cardiac uptake at 99mTc-DPD scintigraphy and AL exclusion). Mutations in TTR were excluded in all cases. The study cohort comprised 108 patients (78.6 ± 8 years); 67 (62%) diagnosed invasively and 41 (38%) non-invasively. Twenty patients (19%) were females. An asymmetric hypertrophy pattern was observed in 25 (23%) patients. Mean LVEF was 52 ± 14%, with 39 patients (37%) showing a LVEF < 50%. Atrial fibrillation (56%) and a pseudo-infarct pattern (63%) were the commonest ECG findings. Only 22 patients fulfilled QRS low-voltage criteria while 10 showed LV hypertrophy on ECG. Although heart failure was the most frequent profile leading to diagnosis (68%), 7% of individuals presented with atrioventricular block and 11% were diagnosed incidentally. Almost one third (35; 32%) were previously misdiagnosed. CONCLUSION: The clinical spectrum of ATTRwt is heterogeneous and differs from the classic phenotype: women are affected in a significant proportion; asymmetric LV hypertrophy and impaired LVEF are not rare and only a minority have low QRS voltages. Clinicians should be aware of the broad clinical spectrum of ATTRwt to correctly identify an entity for which a number of disease-modifying treatments are under investigation.

Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome with multiple underlying causes. Wild-type transthyretin (TTR) amyloidosis (ATTRwt) is an underdiagnosed cause of HFpEF that might benefit from new specific treatments. ATTRwt can be diagnosed non-invasively by (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy. We sought to determine the prevalence of ATTRwt among elderly patients admitted due to HFpEF. METHODS AND RESULTS: We prospectively screened all consecutive patients ≥60 years old admitted due to HFpEF [left ventricular (LV) ejection fraction ≥50%] with LV hypertrophy (≥12 mm). All eligible patients were offered a (99m)Tc-DPD scintigraphy. The study included 120 HFpEF patients (59% women, 82 ± 8 years). A total of 16 patients (13.3%; 95% confidence interval: 7.2-19.5) showed a moderate-to-severe uptake on the (99m)Tc-DPD scintigraphy. All patients with a positive scan underwent genetic testing of the TTR gene, and no mutations were found. An endomyocardial biopsy was performed in four patients, confirming ATTRwt in all cases. There were no differences in age, gender, hypertension, diabetes, coronary artery disease, or atrial fibrillation between ATTRwt patients and patients with other HFpEF forms. Although patients with ATTRwt exhibited higher median N-terminal pro-brain natriuretic peptide (6467 vs. 3173 pg/L; P = 0.019), median troponin I (0.135 vs. 0.025 µg/L; P < 0.001), mean LV maximal wall thickness (17 ± 3.4 vs. 14 ± 2.5 mm; P = 0.001), rate of pericardial effusion (44 vs. 19%; P = 0.047), and rate of pacemakers (44 vs. 12%; P = 0.004), clinical overlap between ATTRwt and other HFpEF forms was high. CONCLUSION: ATTRwt is an underdiagnosed disease that accounts for a significant number (13%) of HFpEF cases. The effect of emerging TTR-modifying drugs should be evaluated in these patients.

Protocolized Natriuresis-Guided Decongestion Improves Diuretic Response: The Multicenter ENACT-HF Study.

BACKGROUND: The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload. METHODS: ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms. RESULTS: Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; P<0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; P<0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; P<0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; P=0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; P=0.852). CONCLUSIONS: A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.

Practical Approaches to the Management of Cardiorenal Disease beyond Congestion.

BACKGROUND: The coexistence of heart and kidney diseases, also called cardiorenal syndrome, is very common, leads to increased morbidity and mortality, and poses diagnostic and therapeutic difficulties. There is a risk-treatment paradox, such that patients with the highest risk are treated with lesser disease-modifying medical therapies. SUMMARY: In this document, different scientific societies propose a practical approach to address and optimize cardiorenal therapies and related comorbidities systematically in chronic cardiorenal disease beyond congestion. Cardiorenal programs have emerged as novel models that may assist in delivering coordinated and holistic management for these patients. KEY MESSAGES: (1) Cardiorenal disease is a ubiquitous entity in clinical practice and is associated with numerous barriers that limit medical treatment. (2) The present article focuses on the practical approaches to managing chronic cardiorenal disease beyond congestion to overcome some of these barriers and improve the treatment of this high-risk population.

Prevalence and clinical profile of kidney disease in patients with chronic heart failure. Insights from the Spanish cardiorenal registry.

INTRODUCTION AND OBJECTIVES: Patients with combined heart failure (HF) and chronic kidney disease (CKD) have been underrepresented in clinical trials. The prevalence of CKD in these patients and their clinical profile require constant evaluation. This study aimed to analyze the prevalence of CKD, its clinical profile, and patterns of use of evidence-based medical therapies in HF across CKD stages in a contemporary cohort of ambulatory patients with HF. METHODS: From October 2021 to February 2022, the CARDIOREN registry included 1107 ambulatory HF patients from 13 HF clinics in Spain. RESULTS: The median age was 75 years, 63% were male, and 48% had heart failure with reduced left ventricular ejection fraction (HFrEF). A total of 654 (59.1%) had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, and 122 (11%) patients with eGFR ≥ 60 mL/min/1.73 m2 had a urine albumin-creatinin ratio ≥ 30 mg/g. The most important variables associated with lower eGFR were age (R2=61%) and furosemide dose (R2=21%). The proportion of patients receiving an angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin II receptor blockers (ARB), an angiotensin receptor-neprilysin inhibitor (ARNi), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), or a mineralocorticoid receptor antagonist (MRA) progressively decreased with lower eGFR categories. Notably, 32% of the patients with HFrEF and an eGFR <30 mL/min/1.73 m2 received the combination of ACEI/ARB/ARNi+beta-blockers+MRA+SGLT2i. CONCLUSIONS: In this contemporary HF registry, 70% of patients had kidney disease. Although this population is less likely to receive evidence-based therapies, structured and specialized follow-up approaches within HF clinics may facilitate the adoption of these life-saving drugs.

Congestion as a crucial factor determining albuminuria in patients with cardiorenal disease.

Background: Albuminuria could potentially emerge as a novel marker of congestion in acute heart failure. However, the current evidence linking albuminuria and congestion in patients with congestive heart failure (CHF) remains somewhat scarce. This study aimed to evaluate the prevalence of albuminuria in a cohort of patients with CHF, identify the independent factors associated with albuminuria and analyse the correlation with different congestion parameters. Methods: This is a subanalysis of the Spanish Cardiorenal Registry, in which we enrolled 864 outpatients with heart failure and a value of urinary albumin:creatinine ratio (UACR) at the first visit. Results: The median age was 74 years, 549 (63.5%) were male and 438 (50.7%) had a reduced left ventricular ejection fraction. A total of 350 patients (40.5%) had albuminuria. Among these patients, 386 (33.1%) had a UACR of 30-300 mg/g and 64 (7.4%) had a UACR >300 mg/g. In order of importance, the independent variables associated with higher UACR were estimated glomerular filtration rate determined by the Chronic Kidney Disease Epidemiology Collaboration equation (R2 = 57.6%), systolic blood pressure (R2 = 21.1%), previous furosemide equivalent dose (FED; R2 = 7.5%), antigen carbohydrate 125 (CA125; R2 = 6.1%), diabetes mellitus (R2 = 5.6%) and oedema (R2 = 1.9%). The combined influence of oedema, elevated CA125 levels and the FED accounted for 15.5% of the model's variability. Conclusions: In patients with chronic stable heart failure, the prevalence of albuminuria is high. The risk factors of albuminuria in this population are chronic kidney disease and hypertension. Congestion parameters are also associated with increased albuminuria.

Clinical impact of remote heart failure management using the multiparameter ICD HeartLogic alert.

INTRODUCTION AND OBJECTIVES: The multiparametric implantable cardioverter-defibrillator HeartLogic index has proven to be a sensitive and timely predictor of impending heart failure (HF) decompensation. We evaluated the impact of a standardized follow-up protocol implemented by nursing staff and based on remote management of alerts. METHODS: The algorithm was activated in HF patients at 19 Spanish centers. Transmitted data were analyzed remotely, and patients were contacted by telephone if alerts were issued. Clinical actions were implemented remotely or through outpatient visits. The primary endpoint consisted of HF hospitalizations or death. Secondary endpoints were HF outpatient visits. We compared the 12-month periods before and after the adoption of the protocol. RESULTS: We analyzed 392 patients (aged 69±10 years, 76% male, 50% ischemic cardiomyopathy) with implantable cardioverter-defibrillators (20%) or cardiac resynchronization therapy defibrillators (80%). The primary endpoint occurred 151 times in 86 (22%) patients during the 12 months before the adoption of the protocol, and 69 times in 45 (11%) patients (P<.001) during the 12 months after its adoption. The mean number of hospitalizations per patient was 0.39±0.89 pre- and 0.18±0.57 postadoption (P<.001). There were 185 outpatient visits for HF in 96 (24%) patients before adoption and 64 in 48 (12%) patients after adoption (P<.001). The mean number of visits per patient was 0.47±1.11 pre- and 0.16±0.51 postadoption (P<.001). CONCLUSIONS: A standardized follow-up protocol based on remote management of HeartLogic alerts enabled effective remote management of HF patients. After its adoption, we observed a significant reduction in HF hospitalizations and outpatient visits.

Usefulness of Systemic Venous Ultrasound Protocols in the Prognosis of Heart Failure Patients: Results from a Prospective Multicentric Study.

Mortality and re-admission rates for decompensated acute heart failure (AHF) is increasing overall and risk stratification might be challenging. We sought to evaluate the prognostic role of systemic venous ultrasonography in patients hospitalized for AHF. We prospectively recruited 74 AHF patients with a NT-proBNP level above 500 pg/mL. Then, multi-organ ultrasound assessments (lung, inferior vena cava (IVC), pulsed-wave Doppler (PW-Doppler) of hepatic, portal, intra-renal and femoral veins) were performed at admission, discharge, and follow-up (for 90 days). We also calculated the Venous Excess Ultrasound System (VExUS), a new score of systemic congestion based on IVC dilatation and pulsed-wave Doppler morphology of hepatic, portal and intra-renal veins. An intra-renal monophasic pattern (area under the curve (AUC) 0.923, sensitivity (Sn) 90%, specificity (Sp) 81%, positive predictive value (PPV) 43%, and negative predictive value (NPV) 98%), a portal pulsatility > 50% (AUC 0.749, Sn 80%, Sp 69%, PPV 30%, NPV 96%) and a VExUS score of 3 corresponding to severe congestion (AUC 0.885, Sn 80%, Sp 75%, PPV 33%, and NPV 96%) predicted death during hospitalization. An IVC above 2 cm (AUC 0.758, Sn 93.l% and Sp 58.3) and the presence of an intra-renal monophasic pattern (AUC 0. 834, sensitivity 0.917, specificity 67.4%) in the follow-up visit predicted AHF-related re-admission. Additional scans during hospitalization or the calculation of a VExUS score probably adds unnecessary complexity to the assessment of AHF patients. In conclusion, VExUS score does not contribute to the guidance of therapy or the prediction of complications, compared with the presence of an IVC greater than 2 cm, a venous monophasic intra-renal pattern or a pulsatility > 50% of the portal vein in AHF patients. Early and multidisciplinary follow-up visits remain necessary for the improvement of the prognosis of this highly prevalent disease.

Predictors and outcomes of pacemaker implantation in patients with cardiac amyloidosis.

OBJECTIVE: We sought to investigate prevalence, incidence and prognostic implications of permanent pacemaker (PPM) implantation in patients with cardiac amyloidosis (CA), thereby identifying the predictors of time to PPM implantation. METHODS: Seven hundred eighty-seven patients with CA (602 men, median age 74 years, 571 transthyretin amyloidosis (ATTR), 216 light-chain amyloidosis (AL)) evaluated at two European referral centres were retrospectively included. Clinical, laboratory and instrumental data were analysed. The associations between PPM implantation and mortality, heart failure (HF) or a composite endpoint of mortality, cardiac transplantation and HF were analysed. RESULTS: 81 (10.3%) patients had a PPM before initial evaluation. Over a median follow-up time of 21.7 months (IQR 9.6-45.2), 81 (10.3%) additional patients (18 with AL (22.2%) and 63 with ATTR (77.8%)) underwent PPM implantation with a median time to implantation of 15.6 months (IQR 4.2-40), complete atrioventricular block was the most common indication (49.4%). Independent predictors of PPM implantation were QRS duration (HR 1.03, 95% CI 1.02 to 1.03, p<0.001) and interventricular septum (IVS) thickness (HR 1.1, 95% CI 1.03 to 1.17, p=0.003). The model to estimate the probability of PPM at 12 months and containing both factors showed a C-statistic of 0.71 and a calibration of slope of 0.98. CONCLUSIONS: Conduction system disease requiring PPM is a common complication in CA that affects up to 20.6% of patients. QRS duration and IVS thickness are independently associated with PPM implantation. A PPM implantation at 12 months model was devised and validated to identify patients with CA at higher risk of requiring a PPM and who require closer follow-up.

Case report: Alternative approach for management of refractory volume overload in heart failure: usefulness of venous leg compression.

Background: Management of patients with refractory congestion, is one of the most important challenges in the field of heart failure (HF). Diuretic therapy remains the most widely used therapy to achieve euvolemia. However, some patients experience fluid overload despite the use of high-dose diuretics and new strategies to overcome diuretic resistance are needed. Case Summary: We report an 85 years-old male patient admitted for decompensated HF with persistent tissue fluid overload (peripheral edema) for more than two weeks despite high dose of intravenous furosemide with the combination of other diuretics. At this point, we performed leg venous compression using elastic bandages for three days. After 72 h, edema disappeared, and additional weight loss was achieved (1 kg/day). No side effects were observed and the patient was discharged home euvolemic. Conclusion: Venous leg compression may be an alternative therapy in patients with persistent tissue fluid overload resistant to diuretics.

Intermittent inotropic support with levosimendan in advanced heart failure as destination therapy: The LEVO-D registry.

AIM: Patients with advanced heart failure (AHF) who are not candidates to advanced therapies have poor prognosis. Some trials have shown that intermittent levosimendan can reduce HF hospitalizations in AHF in the short term. In this real-life registry, we describe the patterns of use, safety and factors related to the response to intermittent levosimendan infusions in AHF patients not candidates to advanced therapies. METHODS AND RESULTS: Multicentre retrospective study of patients diagnosed with advanced heart failure, not HT or LVAD candidates. Patients needed to be on the optimal medical therapy according to their treating physician. Patients with de novo heart failure or who underwent any procedure that could improve prognosis were not included in the registry. Four hundred three patients were included; 77.9% needed at least one admission the year before levosimendan was first administered because of heart failure. Death rate at 1 year was 26.8% and median survival was 24.7 [95% CI: 20.4-26.9] months, and 43.7% of patients fulfilled the criteria for being considered a responder lo levosimendan (no death, heart failure admission or unplanned HF visit at 1 year after first levosimendan administration). Compared with the year before there was a significant reduction in HF admissions (38.7% vs. 77.9%; P < 0.0001), unplanned HF visits (22.7% vs. 43.7%; P < 0.0001) or the combined event including deaths (56.3% vs. 81.4%; P < 0.0001) during the year after. We created a score that helps predicting the responder status at 1 year after levosimendan, resulting in a score summatory of five variables: TEER (+2), treatment with beta-blockers (+1.5), Haemoglobin >12 g/dL (+1.5), amiodarone use (-1.5) HF visit 1 year before levosimendan (-1.5) and heart rate >70 b.p.m. (-2). Patients with a score less than -1 had a very low probability of response (21.5% free of death or HF event at 1 year) meanwhile those with a score over 1.5 had the better chance of response (68.4% free of death or HF event at 1 year). LEVO-D score performed well in the ROC analysis. CONCLUSION: In this large real-life series of AHF patients treated with levosimendan as destination therapy, we show a significant decrease of heart failure events during the year after the first administration. The simple LEVO-D Score could be of help when deciding about futile therapy in this population.

Impact of dapagliflozin on cardiac remodelling in patients with chronic heart failure: The DAPA-MODA study.

AIMS: Dapagliflozin improves the prognosis of patients with heart failure (HF), regardless of left ventricular ejection fraction (LVEF). However, its effect on cardiac remodelling parameters, specifically left atrial (LA) remodelling, is not well established. METHODS AND RESULTS: The DAPA-MODA trial (NCT04707352) is a multicentre, single-arm, open-label, prospective and interventional study that aimed to evaluate the effect of dapagliflozin on cardiac remodelling parameters over 6 months. Patients with stable chronic HF receiving optimized guideline-directed therapy, except for any sodium-glucose cotransporter 2 inhibitor, were included. Echocardiography was performed at baseline, 30 and 180 days, and analysed by a central core-lab in a blinded manner to both patient and time. The primary endpoint was the change in maximal LA volume index (LAVI). A total of 162 patients (64.2% men, 70.5 ± 10.6 years, 52% LVEF >40%) were included in the study. At baseline, LA dilatation was observed (LAVI 48.1 ± 22.6 ml/m2 ) and LA parameters were similar between LVEF-based phenotypes (≤40% vs. >40%). LAVI showed a significant reduction at 180 days (-6.6% [95% confidence interval -11.1, -1.8], p = 0.008), primarily due to a decrease in reservoir volume (-13.8% [95% confidence interval -22.5, -4], p = 0.007). Left ventricular geometry improved with significant reductions in left ventricular mass index (-13.9% [95% confidence interval -18.7, -8.7], p < 0.001), end-diastolic volume (-8.0% [95% confidence interval -11.6, -4.2], p < 0.001) and end-systolic volume (-11.9% [95% confidence interval -16.7, -6.8], p < 0.001) at 180 days. N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed a significant reduction at 180 days (-18.2% [95% confidence interval -27.1, -8.2], p < 0.001), without changes in filling Doppler measures. CONCLUSION: Dapagliflozin administration in stable out-setting patients with chronic HF and optimized therapy results in global reverse remodelling of cardiac structure, including reductions in LA volumes and improvement in left ventricular geometry and NT-proBNP concentrations.

Influence of the medical treatment schedule in new diagnoses patients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) guidelines recommend treating all patients with HF and reduced ejection fraction (HFrEF) with quadruple therapy, although they do not establish how to start it. This study aimed to evaluate the implementation of these recommendations, analyzing the efficacy and safety of the different therapeutic schedules. METHODS AND RESULTS: Prospective, observational, and multicenter registry that evaluated the treatment initiated in patients with newly diagnosed HFrEF and its evolution at 3 months. Clinical and analytical data were collected, as well as adverse reactions and events during follow-up. Five hundred and thirty-three patients were included, selecting four hundred and ninety-seven, aged 65.5 ± 12.9 years (72% male). The most frequent etiologies were ischemic (25.5%) and idiopathic (21.1%), with a left ventricular ejection fraction of 28.7 ± 7.4%. Quadruple therapy was started in 314 (63.2%) patients, triple in 120 (24.1%), and double in 63 (12.7%). Follow-up was 112 days [IQI 91; 154], with 10 (2%) patients dying. At 3 months, 78.5% had quadruple therapy (p < 0.001). There were no differences in achieving maximum doses or reducing or withdrawing drugs (< 6%) depending on the starting scheme. Twenty-seven (5.7%) patients had any emergency room visits or admission for HF, less frequent in those with quadruple therapy (p = 0.02). CONCLUSION: It is possible to achieve quadruple therapy in patients with newly diagnosed HFrEF early. This strategy makes it possible to reduce admissions and visits to the emergency room for HF without associating a more significant reduction or withdrawal of drugs or significant difficulty in achieving the target doses.

Utility of plasma CA125 as a proxy of intra-abdominal pressure in patients with acute heart failure.

AIMS: Increased intra-abdominal pressure (IAP) is now considered a potential contributor to organ damage and disease progression in acute heart failure (AHF). In this work, we aimed to determine if antigen carbohydrate 125 (CA125) is associated with IAP and to identify a cutpoint of CA125 useful for ruling out intra-abdominal hypertension (defined as IAP ≥ 12 mmHg). METHODS AND RESULTS: We prospectively evaluated a cohort of 53 patients admitted with AHF in which IAP was measured within the first 24-h of admission. The mean age was 80 ± 8 years, 31 (58.5%) were female, and 31 (58.5%) had left ventricular ejection fraction ≥50%. The median plasma levels of NT-proBNP and CA125 were 3830 pg/mL (2417-8929) and 45.8 U/mL (29.8-114.0), respectively. The median of IAP was 15 mmHg (11-17), and 39 (73%) patients had an IAP ≥ 12 mmHg. The diagnostic performance of CA125 for identifying an IAP ≥ 12 mmHg was tested using the receiving operating characteristic (ROC) curve. The cut-off for CA125 of 17.1 U/mL showed a sensitivity of 92%, a specificity of 50%, and an area under the ROC curve of 0.71. After multivariate adjustment, CA125 remained non-linearly and positively associated with higher IAP (P-value = 0.003), explaining almost 28% of the model's variability (R2: 27.6%). CONCLUSIONS: Patients with AHF and intra-abdominal hypertension had higher CA125 plasma levels. A baseline concentration of CA125 below 17.1 U/mL will increase the odds of identifying a subset of patients with normal IAP.

Frequency of hereditary transthyretin amyloidosis among elderly patients with transthyretin cardiomyopathy.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a cause of heart failure in the elderly. Although wild-type transthyretin amyloidosis is the most frequent form of ATTR-CM found in the elderly, hereditary transthyretin amyloidosis (ATTRv) can also occur. We sought to determine the prevalence of ATTRv among elderly ATTR-CM patients, identify predictors of ATTRv and evaluate the clinical consequences of positive genetic testing in this population. METHODS AND RESULTS: Prevalence of ATTRv in elderly ATTR-CM patients (≥70 years) was assessed in a cohort of 300 consecutive ATTR-CM patients (median age 78 years at diagnosis, 82% ≥70 years, 16% female, 99% Caucasian). ATTRv was diagnosed in 35 (12%; 95% confidence interval [CI] 3.1-8.8) and 13 (5.3%; 95% CI 5.6-26.7) patients in the overall cohort and in those ≥70 years, respectively. Prevalence of ATTRv among elderly female patients with ATTR-CM was 13% (95% CI 2.1-23.5). Univariate analysis identified female sex (odds ratio [OR] 3.66; 95% CI 1.13-11.85; p = 0.03), black ancestry (OR 46.31; 95% CI 3.52-Inf; p = 0.005), eye symptoms (OR 6.64; 95% CI 1.20-36.73; p = 0.03) and polyneuropathy (OR 10.05; 95% CI 3.09-32.64; p < 0.001) as the only factors associated with ATTRv in this population. Diagnosis of ATTRv in elderly ATTR-CM patients allowed initiation of transthyretin-specific drug treatment in 5 individuals, genetic screening in 33 relatives from 13 families, and identification of 9 ATTRv asymptomatic carriers. CONCLUSIONS: Hereditary transthyretin amyloidosis is present in a substantial number of ATTR-CM patients aged ≥70 years. Identification of ATTRv in elderly patients with ATTR-CM has clinical meaningful therapeutic and diagnostic implications. These results support routine genetic testing in patients with ATTR-CM regardless of age.