Biventricular Takotsubo syndrome complicated with cardiogenic shock and ventricular septal rupture: a case report.

Background: Takotsubo syndrome (TTS) mimics acute coronary syndromes but can lead to serious cardiac complications, emphasizing the need for improved understanding and management. Case summary: We describe a TTS case presented with cardiogenic shock due to ventricular septal rupture (VSR). Successful treatment involved mechanical circulatory support followed by VSR surgical closure. Discussion: Ventricular septal rupture is the rarest and deadliest complication associated with TTS. Prompt recognition and a multidisciplinary approach are crucial to achieve the best possible outcome.

Cardiac magnetic resonance patterns of left ventricular remodeling in patients with severe aortic stenosis referred to surgical aortic valve replacement.

Left ventricular (LV) hypertrophy is a common finding in patients with severe aortic stenosis (AS). Cardiac magnetic resonance (CMR) is the gold-standard technique to evaluate LV remodeling. Our aim was to assess the prevalence and describe the patterns of LV adaptation in AS patients before and after surgical aortic valve replacement (AVR). Prospective study of 130 consecutive patients (71y [IQR 68-77y], 48% men) with severe AS, referred for surgical AVR. Patterns of LV remodeling were assessed by CMR. Besides normal LV ventricular structure, four other patterns were considered: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, and adverse remodeling. At baseline CMR study: mean LV indexed mass: 81.8 ± 26.7 g/m2; mean end-diastolic LV indexed volume: 85.7 ± 23.1 mL/m2 and median geometric remodeling ratio: 0.96 g/mL [IQR 0.82-1.08 g/mL]. LV hypertrophy occurred in 49% of subjects (concentric 44%; eccentric 5%). Both normal LV structure and concentric remodeling had a prevalence of 25% among the cohort; one patient had an adverse remodeling pattern. Asymmetric LV wall thickening was present in 55% of the patients, with predominant septal involvement. AVR was performed in 119 patients. At 3-6 months after AVR, LV remodeling changed to: normal ventricular geometry in 60%, concentric remodeling in 27%, concentric hypertrophy in 10%, eccentric hypertrophy in 3% and adverse remodeling (one patient). Indexes of AS severity, LV systolic and diastolic function and NT-proBNP were significantly different among the distinct patterns of remodeling. Several distinct patterns of LV remodelling beyond concentric hypertrophy occur in patients with classical severe AS. Asymmetric hypertrophy is a common finding and LV response after AVR is diverse.

Histopathological Myocardial Changes in Patients with Severe Aortic Stenosis Referred for Surgical Valve Replacement: A CMR Correlation Study.

Myocardial fibrosis (MF) takes part in left ventricular (LV) remodeling in patients with aortic stenosis (AS), driving the transition from hypertrophy to heart failure. The structural changes that occur in this transition are not fully enlightened. AIM: to describe histopathology changes at endomyocardial biopsy (EMB) in patients with severe AS referred to surgical aortic valve replacement (AVR); to correlate them with LV tissue characterization from pre-operative cardiac magnetic resonance (CMR). METHODS: one-hundred-fifty-eight patients (73[68-77]years, 50%women) referred for surgical AVR because of severe symptomatic AS, with pre-operative CMR (n = 143) with late gadolinium enhancement (LGE), T1, T2 mapping and extracellular volume fraction (ECV) quantification. Intra-operative septal EMB was obtained in 129 patients. MF was assessed through Masson´s Trichrome histochemistry. Immunohistochemistry was performed for both inflammatory cells and extracellular matrix (ECM) characterization (Type I Collagen, Fibronectin, Tenascin C). RESULTS: non-ischemic LGE was present in 106 patients (67.1%) (median fraction:5.0% [2.0-9.7]). Native T1 was above normal: 1053 ms[1024-1071] and T2 within normal range (39.3 ms[37.3-42.0]). Median MF was 11.9%[6.54-19.97], with predominant type I collagen perivascular distribution (95.3%). Subendocardial cardiomyocyte ischemic-like changes were identified in 45% of EMB. There was no inflammation, despite ECM remodeling expression. MF quantification at EMB was correlated with LGE mass (p = 0.008) but not with global ECV (p = 0.125). CONCLUSION: patients with severe symptomatic AS referred for surgical AVR have unspecific histological myocardial changes, including signs of cardiomyocyte ischemic insult. ECM remodeling is ongoing, with MF heterogeneity. These features may be recognized by comprehensive CMR protocols. However, no single CMR parameter captures the burden of MF and histological myocardial changes in this setting.

Subendocardial "ischemic-like" state in patients with severe aortic stenosis: Insights from myocardial histopathology and ultrastructure.

BACKGROUND: Myocardial adaptation to severe aortic stenosis (AS) is a complex process that involves myocardial fibrosis (MF) beyond cardiomyocyte hypertrophy. Perfusion impairment is believed to be involved in myocardial remodeling in chronic pressure overload. AIM: To describe morphological and ultrastructural myocardial changes at endomyocardial tissue sampling, possibly reflecting subendocardial ischemia, in a group of patients with severe AS referred to surgical aortic valve replacement (AVR), with no previous history of ischemic cardiomyopathy. METHODS: One-hundred-fifty-eight patients (73 [68-77] years, 50% women) referred for surgical AVR because of severe symptomatic AS with preoperative clinical and imaging study and no previous history of ischemic cardiomyopathy. Intra-operative septal endomyocardial sampling was obtained in 129 patients. Tissue sections were stained with Masson´s Trichrome for MF quantification and periodic acid-Schiff (PAS) staining was performed to assess the presence of intracellular glycogen. Ultrastructure was analyzed through Transmission electron microscopy (TEM). RESULTS: MF totalized a median fraction of 11.90% (6.54-19.97%) of EMB, with highly prevalent perivascular involvement (95.3%). None of the samples had histological evidence of myocardial infarction. In 58 patients (45%) we found subendocardial groups of cardiomyocytes with cytoplasmatic enlargement, vacuolization and myofiber derangement, surrounded by extensive interstitial fibrosis. These cardiomyocytes were PAS positive, PAS-diastase resistant and Alcian Blue/PAS indicative of the presence of neutral intracellular glyco-saccharides. At TEM there were signs of cardiomyocyte degeneration with sarcomere disorganization and reduction, organelle rarefaction but no signs of intracellular specific accumulation. CONCLUSION: Almost half of the patients with severe AS referred for surgical AVR have histological and ultrastructural signs of subendocardial cardiomyocyte ischemic insult. It might be inferred that local perfusion imbalance contributes to myocardial remodeling and fibrosis in chronic pressure overload.

Is myocardial fibrosis appropriately assessed by calibrated and 2D strain derived integrated backscatter?

AIMS: Increased collagen content of the myocardium modifies tissue reflectivity and integrated backscatter (IBS) indexes are suggested as markers of myocardial fibrosis (MF). We sought to assess the correlation between calibrated (c) IBS and bidimensional (2D) strain derived IBS with left ventricular (LV) MF in patients with severe aortic stenosis (AS). METHODS AND RESULTS: We made a prospective observational cohort study including 157 patients with severe AS referred for surgical aortic valve replacement (AVR), with complete preoperative transthoracic echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) obtained from the anterior basal septum at the time of surgery. Two groups of 30 patients were specifically evaluated, with and without late gadolinium enhancement (LGE) at CMR. IBS was obtained at QRS peak from both parasternal long axis (PLAX) and apical-three-chamber (AP3C) views and measured in decibels (dB). Whole-cardiac cycle IBS at basal anterior septum was obtained from 2D longitudinal strain. Correlation analysis of reflectivity indexes was performed with global and segmental (anterior basal septum) values of native T1 and extracellular volume (ECV), and EMB collagen volume fraction (CVF) (Masson´s Trichrome). IBS values were compared in both group of patients (LGE + vs. LGE -). 60 patients (74 [36-74] years, 45% male) with high gradient (mean gradient: 63 ± 20mmHg), normal flow (45 ± 10mL/m2) AS and preserved left ventricular ejection fraction (60 ± 9%) were included. Basal septum cIBS was - 17.45 (-31.2-10.95) and - 9.17 ± 9.45dB from PLAX and A3C views, respectively. No significant correlations were found between IBS and both non-invasive CMR tissue characterization and CVF: median MF of 9.7(2.1-79.9)%. Acoustic indexes were not significantly different according to the presence of pre-operative LGE. CONCLUSION: In this group of patients with classical severe AS, IBS reflectivity indexes are of no added value to discriminate the presence of MF.

LGE prevalence and patterns in severe aortic stenosis: When "junctional" means the same.

BACKGROUND: Left ventricular (LV) remodeling in severe aortic valve stenosis (AS) is a complex process that goes beyond hypertrophic response. Reparative/replacement fibrosis is considered irreversible and has recognized value in both risk stratification and prognosis. Currently, cardiac magnetic resonance (CMR) is the gold-standard imaging technique for fibrosis identification through late gadolinium enhancement (LGE) assessment. However, its prevalence and distribution are quite variable among series. Our goal was to assess LGE prevalence and patterns in severe AS. METHODOLOGY: Single-center prospective cohort of 140 patients with severe symptomatic high-gradient AS (mean age 72 ± 8 years; mean valvular transaortic gradient 61 ± 18 mmHg; mean LV ejection fraction by echocardiogram 58 ± 9%) undergoing surgical aortic valve replacement. Those with previous myocardial infarction and/or non-ischemic cardiomyopathy were excluded. All patients performed 1.5 T LGE-CMR prior to surgery. RESULTS: Overall, 103 patients (74%) had non-ischemic LGE (median LGE mass 2.8 g [IQR 0.0-7.8] g), many of them with combined mid-wall and junctional enhancement pattern (36%). LGE was most frequently observed in the mid-basal segments of the interventricular septum. Seventy-four patients (53%) had non-exclusively junctional LGE. Contrary to those with junctional enhancement, patients with non-exclusively junctional LGE had higher LV volumes/mass, worse LV ejection fraction and worse global longitudinal strain. CONCLUSION: Among patients with severe, symptomatic, high-gradient AS, LGE is frequent, primarily affecting the mid-basal interventricular septum. Contrary to junctional LGE, the presence of non-junctional LGE seems to correlate with adverse markers of LV remodeling.

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.

Prevalence and significance of relative apical sparing in aortic stenosis: insights from an echo and cardiovascular magnetic resonance study of patients referred for surgical aortic valve replacement.

AIMS: This study aims to assess the prevalence of relative apical sparing pattern (RASP) in patients with severe symptomatic aortic stenosis (AS), referred for surgical aortic valve replacement (AVR), to evaluate its significance, possible relation to amyloid deposition, and persistence after surgery. METHODS AND RESULTS: Prospective study of 150 consecutive patients [age 73 (interquartile range: 68-77), 51% women], with severe symptomatic AS referred to surgical AVR. All patients underwent cardiac magnetic resonance (CMR) before surgery. RASP was defined by [average apical longitudinal strain (LS)/(average basal LS + average mid LS)] > 1 by echocardiography. AVR was performed in 119 (79.3%) patients. Both Congo red and sodium sulphate-Alcian blue (SAB) stain were used to exclude amyloid on septal myocardial biopsy. LV remodelling and tissue characterization parameters were compared in patients with and without RASP. Deformation pattern was re-assessed at 3-6 months after AVR.RASP was present in 23 patients (15.3%). There was no suspicion of amyloid at pre-operative CMR [native T1 value 1053 ms (1025-1076 ms); extracellular volume (ECV) 28% (25-30%)]. None of the patients had amyloid deposition at histopathology. Patients with RASP had significantly higher pre-operative LV mass and increased septal wall thickness. They also had higher N-terminal pro b-type natriuretic peptide (NT-proBNP) levels [1564 (766-3318) vs. 548 (221-1440) pg/mL, P = 0.010], lower LV ejection fraction (53.7 ± 10.5 vs. 60.5 ± 10.2%, P = 0.005), and higher absolute late gadolinium enhancement (LGE) mass [9.7 (5.4-14.1) vs. 4.8 (1.9-8.6) g, P = 0.016] at CMR. Follow-up evaluation after AVR revealed RASP disappearance in all except two of the patients. CONCLUSION: RASP is not specific of cardiac amyloidosis. It may also be found in severe symptomatic AS without amyloidosis, reflecting advanced LV disease, being mostly reversible after surgery.

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.

Life-Threatening Wunderlich Syndrome Associated with Apixaban and the Complexity of Anticoagulation Management in Bleeding Patients: A Case Report.

Wunderlich syndrome is a rare and possibly life-threatening haemorrhagic syndrome presenting as spontaneous nontraumatic renal rupture with subcapsular and perinephric haemorrhage. Apixaban, a direct oral anticoagulant recommended in patients with atrial fibrillation, has previously been associated with atraumatic solid organ rupture but, to date, no case of apixaban-related Wunderlich syndrome has been reported. We report a rare case of Wunderlich syndrome associated with apixaban while addressing the difficulties face by clinicians when managing anticoagulation in bleeding patients.

A síndrome de Wunderlich é uma síndrome hemorrágica rara caracterizada por rutura renal espontânea, não-traumática, com hemorragia subcapsular e peri-renal. O apixabano, um anticoagulante oral direto recomendado em doentes com fibrilação auricular, foi associado no passado a rutura atraumática de órgãos sólidos mas, à data, nenhum caso de síndrome de Wunderlich associada ao apixabano foi reportado. Reportamos um caso raro de síndrome de Wunderlich associada ao apixabano abordando concomitantemente as dificuldades na gestão da anticoagulação em doentes com hemorragia.

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.

Myocardial T1 mapping with magnetic resonance imaging - a useful tool to understand the diseased heart.

Cardiac magnetic resonance imaging (MRI) is increasingly used in clinical practice due to its versatility. T1 mapping of the myocardium, a recently introduced MRI technique that is becoming available enables quantitative tissue characterization, overcoming some of the limitations of late enhancement. This promising technique has the ability to identify diffuse myocardial fibrosis and is beginning to be used in the diagnostic and prognostic assessment of several heart diseases. In this review, we start by explaining the physical principles of myocardial T1 mapping and possible confounding factors in its measurement. We then analyze the evidence supporting its potential usefulness as a complement to the existing cardiac MRI methods. Finally, we discuss the current limitations of T1 mapping and possible areas of future research.

Immunoglobulin G4-related constrictive pericarditis and the importance of a thorough workup: a case report.

BACKGROUND: Constrictive pericarditis remains a problematic diagnosis and a thorough investigation is critical. Among possible aetiologies, immunoglobulin-G4 (IgG4)-related pericardial disease is an unusual cause of pericardial constriction. We report a challenging diagnostic case of pericardial constriction due to IgG4-related disease. CASE PRESENTATION: A 68-year old male with a history of inferior myocardial infarction with right ventricle (RV) involvement was thrice-hospitalized due to marked ascites and peripheral oedema. Systemic congestion was initially attributed to RV dysfunction due to previous infarction. Yet, at the final admission, a re-assessment echocardiogram followed by cardiac computed tomography, magnetic resonance and right heart catheterization raised a possible diagnosis of constrictive pericarditis with a finding of abnormal pulmonary venous return. Patient therefore underwent pericardiectomy and surgical correction of pulmonary venous return. Pericardium histology revealed an IgG4-related pericardial constriction. Patient was later discharged on corticosteroids with marked symptomatic improvement. CONCLUSION: IgG4-related disease remains a rare cause of pericardium constriction while also presenting a challenging diagnosis in everyday clinical practice. This case exemplifies the difficulties faced by clinicians when reviewing a possible case of constrictive pericarditis, while highlighting the importance of a multimodality assessment.

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.

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.