Acute kidney injury patterns in acute heart failure: The prognostic value of worsening renal function and its timing.

INTRODUCTION: Acute decompensated heart failure (ADHF) admissions are frequently complicated by different patterns of serum creatinine (SCr) elevation. We aimed to assess the prognostic impact of worsening renal function (WRF) based on the timing of its occurrence. METHODS: This was a retrospective cohort of patients admitted for ADHF. Standard WRF was defined as an increase in SCr of ≥0.3 mg/dl during hospitalization. WRF timing was classified as early (within 48 hours of admission) or late (>48 hours). Acute kidney injury (AKI) at admission was defined as a rise in SCr of ≥0.3 mg/dl from outpatient baseline measurement to first measurement at admission. The primary endpoint was a composite of all-cause mortality or hospitalization for cardiovascular events at one-year follow-up. RESULTS: Overall, 249 patients were included (mean age 77±11 years, 62% with preserved left ventricular ejection fraction). Early WRF occurred in 49 patients (19.7%) and was associated with a higher risk of the primary outcome (HR 2.49; 95% CI 1.66-3.73), whereas late WRF was not (p=0.411). After stratification for the presence of early WRF and/or AKI at admission, only patients with early WRF but no AKI at admission and patients with both AKI at admission and early WRF showed a higher risk of the primary outcome after multivariate Cox regression. CONCLUSION: Early WRF was associated with a higher risk of the primary outcome. The timing of WRF seems to be an important factor to take into account when considering the prognostic impact of creatinine variations during hospitalization for ADHF.

Beyond exercise oscillatory ventilations: the prognostic impact of loop gain in heart failure.

Exercise oscillatory ventilation (EOV) is a strong prognostic marker in patients with heart failure (HF) and left ventricular (LV) dysfunction. This phenomenon can be explained through a single quantitative measurement of ventilatory instability, the loop gain. Therefore, we aimed to evaluate whether loop gain could be a better tool than subjective EOV evaluation to identify HF patients with a higher risk of major cardiovascular complications. This was a single-center retrospective study that included patients with left ventricular ejection fraction (LVEF) ≤ 50% consecutively referred for cardiopulmonary exercise testing (CPET) from 2016-2020. Loop gain was measured through computational evaluation of the minute ventilation graph. Of the 250 patients included, the 66 that presented EOV also had higher values of loop gain, when compared to patients without EOV. Those with both EOV and higher loop gain had more severe HF, with higher NT-proBNP and VE/VCO2 slope as well as lower peak VO2 and LVEF. On multivariable analysis, loop gain was strongly correlated with the composite endpoint of cardiovascular death, urgent heart transplantation, urgent left ventricular assist device implantation or HF hospitalization, even after correcting for peak VO2, LVEF, VE/VCO2 slope and NT-proBNP. Presence of EOV was not prognostically significant in this analysis. Loop gain is an objective parameter that quantifies ventilatory instability and showed to have a strong prognostic value in a cohort of patients with HF and LVEF ≤ 50%, outperforming the classification of EOV.

Loop gain is an objective parameter that quantifies ventilatory instability and demonstrated strong prognostic value in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) ≤ 50%. Loop gain was strongly correlated with the composite endpoint of cardiovascular death, urgent heart transplantation, urgent left ventricular assist device implantation or HF hospitalization, even after correcting for peak VO2, LVEF, VE/VCO2 slope and NT-proBNP. Presence of exercise oscillatory ventilation was not prognostically significant when added to loop gain measurement.

Clinical outcomes in heart failure with reduced left ventricular ejection fraction and good functional capacity: The illusion of stability.

BACKGROUND: Heart failure (HF) remains a prevalent syndrome with significant morbidity and mortality. Optimal drug and device therapies are crucial to reduce the risk of death or HF admission. Yet, less symptomatic patients with good functional capacity are often perceived as having a low risk of adverse events and their attending physicians may suffer from prescription inertia or refrain from performing therapy optimization. Maximum or peak oxygen consumption (pVO2) assessed during cardiopulmonary exercise testing (CPET) is often used as a prognosis indicator and surrogate marker for functional capacity. Our goal was to assess clinical outcomes in a seemingly low risk HF population in Weber class A (pVO2>20 mL/kg/min) with reduced left ventricular ejection fraction (LVEF). METHODS: Single-center retrospective observational study enrolling consecutive HF patients with LVEF<40% (HFrEF) performing CPET between 2003 and 2018. Those with pVO2 >20 mL/kg/min were included. The primary endpoint was a composite of all-cause death or HF hospitalizations at two years after CPET. We also assessed the rates of N-terminal pro b-type natriuretic peptide (NT-proBNP) elevations at baseline. RESULTS: Seventy-two patients were included (mean age of 53±10 years; 86% male; 90% NYHA I-II; median LVEF 32%; median pVO2 24 mL/kg/min). At baseline, 93% had an NT-proBNP level >125 pg/mL (median NT-proBNP 388 [201-684] pg/mL). Overall, seven patients (10%) met the primary endpoint: three died (4%) and five (7%) had at least one HF admission. Among those who died, only one patient had an HF admission during follow up. CONCLUSION: In a clinically stable HFrEF population with good functional capacity, persistent neurohormonal activation was present in the majority, and one in ten patients died or had a HF admission at two years' follow-up. These findings support the urgent need to motivate clinicians to pursue optimal drug uptitration even in less symptomatic patients.

Predicting obstructive coronary artery disease in heart failure with reduced ejection fraction: A practical clinical score.

INTRODUCTION AND OBJECTIVES: Obstructive coronary artery disease (CAD) remains the most common etiology of heart failure with reduced ejection fraction (HFrEF). However, there is controversy whether invasive coronary angiography (ICA) should be used initially to exclude CAD in patients presenting with new-onset HFrEF of unknown etiology. Our study aimed to develop a clinical score to quantify the risk of obstructive CAD in these patients. METHODS: We performed a cross-sectional observational study of 452 consecutive patients presenting with new-onset HFrEF of unknown etiology undergoing elective ICA in one academic center, between January 2005 and December 2019. Independent predictors for obstructive CAD were identified. A risk score was developed using multivariate logistic regression of designated variables. The accuracy and discriminative power of the predictive model were assessed. RESULTS: A total of 109 patients (24.1%) presented obstructive CAD. Six independent predictors were identified and included in the score: male gender (2 points), diabetes (1 point), dyslipidemia (1 point), smoking (1 point), peripheral arterial disease (1 point), and regional wall motion abnormalities (3 points). Patients with a score ≤3 had less than 15% predicted probability of obstructive CAD. Our score showed good discriminative power (C-statistic 0.872; 95% CI 0.834-0.909: p<0.001) and calibration (p=0.333 from the goodness-of-fit test). CONCLUSIONS: A simple clinical score showed the ability to predict the risk of obstructive CAD in patients presenting with new-onset HFrEF of unknown etiology and may guide the clinician in selecting the most appropriate diagnostic modality for the assessment of obstructive CAD.

A case report of arrhythmogenic mitral valve disease: still a long way to go.

Background: Mitral valve prolapse (MVP) is a common valvular heart disease and has often been associated with an increased risk of sudden cardiac death (SCD). This underlines the pressing need for the establishment of consistent tools for arrhythmic risk prediction. Case summary: A 73-year-old man with previous diagnosis of MVP was referred to the cardiology outpatient consult for a 1-month history of near-syncope and light-headedness. He had no family history of SCD. Physical examination was unremarkable. Holter monitoring recorded frequent and multiple long episodes of non-sustained ventricular tachycardia (VT) and paroxysmal atrial fibrillation with controlled ventricular response. Echocardiogram revealed mitral bileaflet billowing, systolic curling, and annular disjunction, as well as increased peak systolic strain dispersion with two-dimensional speckle tracking. Cardiac magnetic resonance disclosed additional tricuspid annular dilatation and disjunction, as non-ischaemic late gadolinium enhancement on the left ventricular basal inferolateral wall. The Heart Team decided to implant a defibrillator as primary prevention for SCD due to arrhythmogenic mitral valve disease (AMVD) with high-risk features. The patient remained asymptomatic over the next 2 years, when he suffered an appropriate shock due to VT at 200 b.p.m. Discussion: Here, we present a case of a patient with AMVD with classic features of high arrhythmic risk but also with some unusual characteristics such as older age, male gender, and only little pronounced mitral valve billowing, emphasizing the wide heterogeneity and lack of knowledge surrounding this entity.

The updated pre-test probability model of the 2019 ESC guidelines improves prediction of obstructive coronary artery disease.

INTRODUCTION AND OBJECTIVES: The 2019 ESC guidelines on chronic coronary syndromes updated the method for estimating the pre-test probability (PTP) of obstructive coronary artery disease (CAD). We aimed to compare the performance of the new PTP method against the 2013 prediction model in patients with stable chest pain undergoing coronary computed tomography angiography (CCTA) for suspected CAD. METHODS: We conducted a single-center cross-sectional study enrolling 320 consecutive patients undergoing CCTA for suspected CAD. Obstructive CAD was defined as any ≥50% luminal stenosis on CCTA. Whenever invasive coronary angiography was subsequently performed, patients were reclassified accordingly. The two PTP prediction models were assessed for calibration, discrimination and the ability to change the downstream diagnostic pathway. RESULTS: The observed prevalence of obstructive CAD was 16.3% (n=52). The 2013 prediction model significantly overestimated the likelihood of obstructive CAD (relative overestimation of 130%, p=0.005), while the updated 2019 method showed good calibration (relative underestimation of 6.5%, p=0.712). The two approaches showed similar discriminative power, with C-statistics of 0.73 (95% CI: 0.66-0.80) and 0.74 (95% CI: 0.66-0.81) for the 2013 and 2019 methods, respectively (p=0.933). Reclassification of PTP using the new method resulted in a net reclassification improvement of 0.10 (p=0.001). CONCLUSIONS: The updated 2019 prediction model provides a more accurate estimation of pre-test probabilities of obstructive CAD than the previous model. Adoption of this new score may improve disease prediction and influence the selection of non-invasive testing.

Pectoralis major muscle quantification by cardiac MRI is a strong predictor of major events in HF.

Clinical overt cardiac cachexia is a late ominous sign in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The main goal of this study was to assess the feasibility and prognostic significance of muscle mass quantification by cardiac magnetic resonance (CMR) in HF with reduced LVEF. HF patients with LVEF < 40% (HFrEF) referred for CMR were retrospectively identified in a single center. Key exclusion criteria were primary muscle disease, known infiltrative myocardial disease and intracardiac devices. Pectoralis major muscles were measured on standard axial images at the level of the 3rd rib anteriorly. Time to all-cause death or HF hospitalization was the primary endpoint. A total of 298 HF patients were included (mean age 64 ± 12 years; 76% male; mean LVEF 30 ± 8%). During a median follow-up of 22 months (IQR: 12-33), 67 (22.5%) patients met the primary endpoint (33 died and 45 had at least 1 HF hospitalization). In multivariate analysis, LVEF [Hazard Ratio (HR): 0.950; 95% Confidence Interval (CI): 0.917-0.983; p = 0.003), NYHA class I-II vs III-IV (HR: 0.480; CI: 0.272-0.842; p = 0.010), creatinine (HR: 2.653; CI: 1.548-4.545; p < 0.001) and pectoralis major area (HR: 0.873; 95% CI: 0.821-0.929; p < 0.001) were independent predictors of the primary endpoint, when adjusted for gender and NT-pro-BNP levels. Pectoralis major size measured by CMR in HFrEF was independently associated with a higher risk of death or HF hospitalization. Further studies to establish appropriate age and gender-adjusted cut-offs of muscle areas are needed to identify high-risk subgroups.

Sleep-disordered breathing patterns in hospitalized patients with acute heart failure across the entire spectrum of ejection fraction.

BACKGROUND: Sleep-disordered breathing (SDB) is prevalent in heart failure (HF). Yet, scarce data exist on sleep-patterns in acute HF and differences in specific subgroups. Our goal was to assess SDB prevalence in hospitalized patients with decompensated HF across the entire spectrum of left ventricle ejection fraction (LVEF). METHODS: Single-center retrospective study enrolling patients admitted for acute HF between 2013 and 2018. All patients were screened for SDB with an ApneaLink™ Plus device before discharge while euvolemic and receiving oral therapy. Those with a sleep study time < 3 h were excluded. HF with reduced, moderately reduced, and preserved LVEF (HFrEF, HFmrEF, and HFpEF) was defined by a LVEF < 40%, 40-49%, and ≥ 50%, respectively. SDB was defined by an apnea-hypopnea index (AHI) ≥ 5/h. RESULTS: Overall, 221 patients were included (mean age 75 ± 11 years). Seventy-two (33%) had HFrEF, 26 (11%) HFmrEF, and 123 (56%) HFpEF. In total, 176 (80%) met the criteria for mild SDB, while 59% and 38% had an AHI ≥ 15/h or ≥ 30/h, respectively. SDB prevalence was high and similar between HFrEF, HFmrEF, and HFpEF. Yet, SDB was often more severe in HFrEF when compared to HFpEF. HFmrEF had intermediate characteristics, with an AHI closer to HFrEF. CONCLUSION: In a cohort of patients admitted for acute HF, SDB was highly prevalent in all subgroups, including HFmrEF. The pervasiveness and severity of SDB was particularly noted in HFrEF. These findings suggest that routine SDB screening may be warranted following acute HF.

Measuring lung water adds prognostic value in heart failure patients undergoing cardiac magnetic resonance.

To assess whether a simplified cardiac magnetic resonance (CMR)-derived lung water density (LWD) quantification predicted major events in Heart Failure (HF). Single-centre retrospective study of consecutive HF patients with left ventricular ejection fraction (LVEF) < 50% who underwent CMR. All measurements were performed on HASTE sequences in a parasagittal plane at the right midclavicular line. LWD was determined by the lung-to-liver signal ratio multiplied by 0.7. A cohort of 102 controls was used to derive the LWD upper limit of normal (21.2%). The primary endpoint was a composite of time to all-cause death or HF hospitalization. Overall, 290 patients (mean age 64 ± 12 years) were included. LWD measurements took on average 35 ± 4 s, with good inter-observer reproducibility. LWD was increased in 65 (22.4%) patients, who were more symptomatic (NYHA ≥ III 29.2 vs. 1.8%; p = 0.017) and had higher NT-proBNP levels [1973 (IQR: 809-3766) vs. 802 (IQR: 355-2157 pg/mL); p < 0.001]. During a median follow-up of 21 months, 20 patients died and 40 had ≥ 1 HF hospitalization. In multivariate analysis, NYHA (III-IV vs. I-II; HR: 2.40; 95%-CI: 1.30-4.43; p = 0.005), LVEF (HR per 1%: 0.97; 95%-CI: 0.94-0.99; p = 0.031), serum creatinine (HR per 1 mg/dL: 2.51; 95%-CI: 1.36-4.61; p = 0.003) and LWD (HR per 1%: 1.07; 95%-CI: 1.02-1.12; p = 0.007) were independent predictors of the primary endpoint. These findings were mainly driven by an association between LWD and HF hospitalization (p = 0.026). A CMR-derived LWD quantification was independently associated with an increased HF hospitalization risk in HF patients with LVEF < 50%. LWD is a simple, reproducible and straightforward measurement, with prognostic value in HF.

Dapagliflozin in a Real-World Chronic Heart Failure Population: How Many Are Actually Eligible?

BACKGROUND: In patients with heart failure (HF) and reduced ejection fraction (HFrEF) with or without type 2 diabetes mellitus, the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin was recently shown to reduce the risk of worsening HF or death from cardiovascular causes in the dapagliflozin in patients with heart failure and reduced ejection fraction (DAPA-HF) trial. Our goal was to investigate how many patients in a real-world setting would be eligible for dapagliflozin according to the DAPA-HF enrolment criteria. METHODS: This is a single-center retrospective study enrolling consecutive, unselected patients followed up in an HF clinic from 2013 to 2019. Key DAPA-HF inclusion criteria (i.e., left ventricular ejection fraction [LVEF] ≤40% and NT-proBNP ≥600 pg/mL [or ≥900 pg/mL if atrial fibrillation]) and exclusion criteria (estimated glomerular filtration rate [eGFR] <30 mL/kg/1.73 m2 and systolic blood pressure [SBP] <95 mm Hg) were considered. RESULTS: Overall, 479 patients (age 76 ± 13 years; 50.5% male; 78.9% hypertensive; 45.1% with an eGFR <60 mL/min/1.73 m2; 36.5% with TD2M; and 33.5% with ischaemic HF) were assessed. The median SBP was 128.5 (112.0-146.0) mm Hg, mean eGFR was 50.8 ± 23.7 mL/min/1.73 m2, and median NT-proBNP was 2,183 (IQR 1,010-5,310) pg/mL. Overall, 155 (32.4%) patients had LVEF ≤40%. According to the DAPA-HF trial key criteria, 90 patients (18.8%) would be eligible for dapagliflozin. The remainder would be excluded due to LVEF >40% (67.6%), eGFR <30 mL/min/1.73 m2 (19.4%), NT-proBNP below the cutoff (16.7%), and/or SBP <95 mm Hg (6.5%). If we center the analysis to those with LVEF ≤40%, 58.1% would be eligible for dapagliflozin. The remainder would be excluded due to an eGFR <30 mL/min/1.73 m2 (20%), NT-proBNP below the cutoff (16.1%), and/or SBP <95 mm Hg (8.4%). CONCLUSION: Roughly half of our real-world HFrEF cohort would be eligible for dapagliflozin according to the key criteria of the DAPA-HF trial. The main reason for non-eligibility was an eGFR <30 mL/min/1.73 m2. However, two-thirds of patients had LVEF >40%. These findings show that dapagliflozin is a promising complementary new drug in the therapeutic armamentarium of most patients with HFrEF, while highlighting the urgent need for disease-modifying drugs in mid-range and preserved LVEF and the need to assess the efficacy and safety of SLGT2i in advanced kidney disease patients. The results of ongoing SGLT2i trials in these LVEF subgroups are eagerly awaited.

Fulminant Eosinophilic Myocarditis: A Rare and Life-Threatening Presentation of Eosinophilic Granulomatosis With Polyangiitis.

We describe a case of fulminant eosinophilic myocarditis as the first presentation of eosinophilic granulomatosis with polyangiitis, promptly managed with extracorporeal membrane oxygenation. This case highlights the multidisciplinary work involving all health care professionals in the acute management of these patients and discusses it from an educational point of view. (Level of Difficulty: Intermediate.).

Diagnostic and therapeutic approach to cardioinhibitory reflex syncope: A complex and controversial issue. / Abordagem diagnóstica e terapêutica da síncope reflexa cardio­inibitória ­ A complexidade de um tema controverso.

Syncope is defined as a transient loss of consciousness due to global cerebral hypoperfusion and is one of the leading causes of emergency department admission. The initial approach should focus on excluding non-syncopal causes for loss of consciousness and risk stratification for cardiac cause, in order to ensure an appropriate etiological investigation and therapeutic approach. Vasovagal syncope (VVS), the most common type of syncope, should be assumed once other causes are excluded. Pathophysiologically, the vasovagal reflex is the result of a paradoxical autonomic response, leading to hypotension and/or bradycardia. VVS has not been shown to affect mortality, but morbidity may be considerable in those with recurrent syncopal episodes. The management of VVS includes both non-pharmacological and pharmacological measures that act on various levels of the reflex arc that triggers the syncopal episode. However, most are of uncertain benefit given the scarcity of high-quality supporting evidence. Pacemaker therapy may be considered in recurrent refractory cardioinhibitory reflex syncope, for which it is currently considered a robust intervention, as noted in the European guidelines. Non-randomized and unblinded studies have shown a potential benefit of pacing in recurrent VVS, but double-blinded randomized controlled trials have not consistently demonstrated positive results. We performed a comprehensive review of the current literature and recent advances in cardiac pacing and pacing algorithms in VVS, and discuss the diagnostic and therapeutic approach to the complex patient with recurrent VVS and reduced quality of life.

Iron deficiency in chronic and acute heart failure: A contemporary review on intertwined conditions.

Iron Deficiency (ID) is increasingly recognized as a prevalent comorbid condition in Heart Failure (HF). Despite this, the pathophysiological mechanisms for progressive ID in either chronic or acute HF are still poorly understood. Beyond the traditional factors for iron deficit in the general population, we ought to review the specificities of such paucity in the HF patient, particularly focusing on the interplay between heightened inflammation, overactivity of the sympathetic nervous system and the so-called cardio-renal-anaemia-ID syndrome. Currently, ID constitutes not only an independent prognostic marker but also a novel safe therapeutic target. Particularly, in selected stable HF patients with reduced left ventricular ejection fraction, intravenous (IV) iron improves symptomatic burden and reduces hospitalizations due to worsening HF. On this topic, the main trials of IV iron with either iron sucrose (Toblli et al., FERRIC-HF and IRON-HF) or ferric carboxymaltose (FAIR-HF, CONFIRM-HF and EFFECT-HF) will be summarized and discussed. Finally, we debate the gaps in knowledge of ID in special populations, namely the unreliability of routine plasmatic surrogate markers to assess iron status in acute and advanced HF, the challenging patient with both HF and Chronic Kidney Disease, as well as efficacy and safety concerns in these settings and the potential role of iron correction in cardiac resynchronization therapy candidates.

The Burden of Iron Deficiency in Heart Failure: Therapeutic Approach.

Heart failure (HF) is highlighted by its burdening symptom-limited exercise capacity and recurrent hospitalizations. Despite substantial advances regarding disease-modifying drugs in HF with reduced ejection fraction, additional therapeutic strategies to improve quality of life are invaluable. Currently, iron deficiency (ID) is overwhelmingly recognized in over 30% to 50% of patients with stable chronic HF, which worsens prognosis. The established pathophysiological mechanisms of progressive HF may be intertwined with increasing myocardial iron scarcity, wherein one begets the other. Most importantly, ID constitutes a novel target for symptom relief in carefully selected patients. In this regard, intravenous iron may be a safe and efficacious intervention, potentially reducing HF hospitalizations. We discuss the evidence and gaps in knowledge concerning iron therapy in HF and propose a practical, comprehensive, clinically oriented algorithm for timely adequate iron replenishment in different clinical scenarios. Finally, we further debate imperative decision-making before intervention and the drawbacks of such a strategy.