Comparison of a Pure Plug-Based Versus a Primary Suture-Based Vascular Closure Device Strategy for Transfemoral Transcatheter Aortic Valve Replacement: The CHOICE-CLOSURE Randomized Clinical Trial.

BACKGROUND: Transcatheter aortic valve replacement is an established treatment option for patients with severe symptomatic aortic stenosis and is most commonly performed through the transfemoral access route. Percutaneous access site closure can be achieved using dedicated plug-based or suture-based vascular closure device (VCD) strategies, but randomized comparative studies are scarce. METHODS: The CHOICE-CLOSURE trial (Randomized Comparison of Catheter-based Strategies for Interventional Access Site Closure during Transfemoral Transcatheter Aortic Valve Implantation) is an investigator-initiated, multicenter study, in which patients undergoing transfemoral transcatheter aortic valve replacement were randomly assigned to vascular access site closure using either a pure plug-based technique (MANTA, Teleflex) with no additional VCDs or a primary suture-based technique (ProGlide, Abbott Vascular) potentially complemented by a small plug. The primary end point consisted of access site- or access-related major and minor vascular complications during index hospitalization, defined according to the Valve Academic Research Consortium-2 criteria. Secondary end points included the rate of access site- or access-related bleeding, VCD failure, and time to hemostasis. RESULTS: A total of 516 patients were included and randomly assigned. The mean age of the study population was 80.5±6.1 years, 55.4% were male, 7.6% of patients had peripheral vascular disease, and the mean Society of Thoracic Surgeons score was 4.1±2.9%. The primary end point occurred in 19.4% (50/258) of the pure plug-based group and 12.0% (31/258) of the primary suture-based group (relative risk, 1.61 [95% CI, 1.07-2.44], P=0.029). Access site- or access-related bleeding occurred in 11.6% versus 7.4% (relative risk, 1.58 [95%CI: 0.91-2.73], P=0.133) and device failure in 4.7% versus 5.4% (relative risk, 0.86, [95% CI, 0.40-1.82], P=0.841) in the respective groups. Time to hemostasis was significantly shorter in the pure plug-based group (80 [32-180] versus 240 [174-316] seconds, P<0.001). CONCLUSIONS: Among patients treated with transfemoral transcatheter aortic valve replacement, a pure plug-based vascular closure technique using the MANTA VCD is associated with a higher rate of access site- or access-related vascular complications but a shorter time to hemostasis compared with a primary suture-based technique using the ProGlide VCD. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04459208.

Comparison of Percutaneous Coronary Intervention Procedures and Outcomes for Recent and Acute ST-Elevation Myocardial Infarction.

Although the primary percutaneous coronary intervention (PCI) is an established treatment for acute ST-elevation myocardial infarction (STEMI), relevant guidelines do not recommend it for recent-STEMI cases with a totally occluded infarcted related artery (IRA). However, PCI is allowed in Japan for recent-STEMI cases, but little is known regarding its outcomes. We aimed to examine the details and outcomes of PCI procedures in recent-STEMI cases with a totally occluded IRA and compared the findings with those in acute-STEMI cases.Among the 903 consecutive patients admitted with acute coronary syndrome, 250 were treated with PCI for type I STEMI with a totally occluded IRA. According to the time between symptom onset and diagnosis, patients were divided into the recent-STEMI (n = 32) and acute-STEMI (n = 218) groups. The background, procedure details, and short-term outcomes were analyzed. No significant differences between the groups were noted regarding patient demographics, acute myocardial infarction severity, or IRA distribution. Although the stent number and type were similar, significant differences were observed among PCI procedures, including the number of guidewires used, rate of microcatheter or double-lumen catheter use, and application rate of thrombus aspiration. The thrombolysis rate in the myocardial infarction flow 3-grade post-PCI did not differ significantly between the groups. Both groups had a low frequency of procedure-related complications. The in-hospital mortality rates were 0% and 4.6% in the recent-STEMI and acute-STEMI groups, respectively (P > 0.05).Although recent-STEMI cases required complicated PCI techniques, their safety, success rate, and in-hospital mortality were comparable to those of acute-STEMI cases.

12-Month outcomes of transcatheter tricuspid valve repair with the PASCAL system for severe tricuspid regurgitation.

OBJECTIVES: We investigated the durability of tricuspid regurgitation (TR) reduction and the clinical outcomes through 12 months after transcatheter tricuspid valve repair (TTVr) with the PASCAL Transcatheter Valve Repair System. BACKGROUND: TTVr has rapidly developed and demonstrated favorable acute outcomes, but longer follow-up data are needed. METHODS: Overall, 30 patients (age 77 ± 6 years; 57% female) received PASCAL implantation from September 2017 to May 2019 and completed a clinical follow-up at 12 months. RESULTS: The TR etiology was functional in 25 patients (83%), degenerative in three (10%), and mixed in two (7%). All patients had TR severe or greater (massive or torrential in 80%) and heart failure symptoms (90% in NYHA III or IV) under optimal medical treatment. Single-leaflet device attachment occurred in two patients. Moderate or less TR was achieved in 23/28 patients (82%) at 30 days, which was sustained at 12 months (86%). Two patients underwent repeat TTVr due to residual torrential TR (day 173) and recurrence of severe TR (day 280), respectively. One-year survival rate was 93%; 6 patients required rehospitalization due to acute heart failure. NYHA functional class I or II was achieved in 90% and 6-minute walk distance improved from 275 ± 122 m at baseline to 347 ± 112 m at 12-month (+72 ± 82 m, p < .01). There was no stroke, endocarditis, or device embolization during the follow-up. CONCLUSIONS: Twelve-month outcomes from this multicenter compassionate use experience with the PASCAL System demonstrated high procedural success, acceptable safety, and significant clinical improvement.

Distribution of C-arm projections in native and bioprosthetic aortic valves cusps: Implication for BASILICA procedures.

OBJECTIVES: We sought to document aortic cusps fluoroscopic projections and their distributions using leaflet alignment which is a novel concept to optimize visualization of leaflets and for guiding BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent coronary artery obstruction) and determine whether these projections were feasible in catheter laboratory. BACKGROUND: Optimal fluoroscopic projections of aortic valve cusps have not been well described. METHODS: A total of 128 pre-transcatheter aortic valve replacement (pre-TAVR) computed tomographies (CT) (72 native valves and 56 bioprosthetic surgical valves) were analyzed. Using CT software (3Mensio, Pie medical imaging, the Netherlands), leaflet alignment was performed and the feasibility of these angles, which were defined as rate of obtainable with efforts (within LAO/RAO of 85° and CRA/CAU of 50°) were evaluated. RESULTS: High feasibility was seen in right coronary cusp (RCC) front view (100%) and left coronary cusp (LCC) side view (99.2%), followed by noncoronary cusp side view (95.3%). In contrast, low feasibility of RCC side view (7.8%) and LCC front view (47.6%) was observed. No statistical differences were seen between the distribution of native valves and bioprosthetic surgical valves. With patient/table tilt of 20°LAO and 10°CRA, the feasibility of RCC side view and LCC front view increased to 43.7 and 85.2%, respectively. CONCLUSION: Distributions of each cusp's leaflet alignment follows "sigmoid curve" which can provide better understanding of aortic valve cusp orientation in TAVR and BASILICA. RCC side view used in right cusp BASILICA is commonly unachievable in catheter laboratory and may improve with patient/table tilt.

Relationship Between Procedural Right Bundle Branch Block and 1-Year Outcome After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy　- A Retrospective Study.

BACKGROUND: Alcohol septal ablation (ASA) is a treatment option in patients with drug-refractory symptomatic hypertrophic obstructive cardiomyopathy (HOCM). In many patients, right bundle branch block (RBBB) develops during ASA because septal branches supply the right bundle branch. However, the clinical significance of procedural RBBB is uncertain.Methods and Results:We retrospectively reviewed 184 consecutive patients with HOCM who underwent ASA. We excluded 40 patients with pre-existing RBBB (n=10), prior pacemaker implantation (n=15), mid-ventricular obstruction type (n=10), and those lost to follow-up (n=5), leaving 144 patients for analysis. Patients were divided into 2 groups according to the development (n=95) or not (n=49) of procedural RBBB. ASA conferred significant decreases in the left ventricular pressure gradient (LVPG) in both the RBBB and no-RBBB group (from 74±48 to 27±27 mmHg [P<0.001] and from 75±45 to 31±33 mmHg [P<0.001], respectively). None of the RBBB patients developed further conduction system disturbances. The percentage reduction in LVPG at 1 year after the procedure was significantly greater in the RBBB than no-RBBB group (66±24% vs. 49±45%; P=0.035). Procedural RBBB was not associated with pacemaker implantation after ASA, but was associated with reduction in repeat ASA (odds ratio 0.34; 95% confidence interval 0.13-0.92; P=0.045). CONCLUSIONS: Although RBBB frequently occurs during the ASA procedure, it does not adversely affect clinical outcomes.

Percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy through non-left anterior descending septal perforators.

Percutaneous transluminal septal myocardial ablation (PTSMA) has become a significant treatment for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) despite maximal medical therapy. The target septal arteries usually arise from the left anterior descending artery (LAD). However, when septal perforators do not originate from the LAD, non-LAD septal perforators should be included as candidate-target septal branches that feed the hypertrophic septal myocardium, causing left ventricular outflow tract (LVOT) obstruction. Data pertaining to the procedure remain limited. We aimed to investigate PTSMA through the non-LAD septal perforators in patients with HOCM. In this case series review, we evaluated the baseline characteristics, echocardiographic features, and angiographic features, as well as symptoms and pressure gradient before and after PTSMA through the non-LAD septal perforators. Among 202 consecutive patients who underwent PTSMA for HOCM with LVOT obstruction, 21 had non-LAD septal branches that fed the hypertrophic septal myocardium and received alcohol ablation. Non-LAD septal perforators could be used as an alternative route for PTSMA in patients who experienced ineffective ablation of the septal branch that arises from the LAD. This unique procedure may improve response rates and overall outcomes of patients with HOCM.

MitraClip in Patients With Mitral Regurgitation and Left Ventricular Ejection Fraction <30%　- Potential Implications for the Treatment of Patients in Japan.

BACKGROUND: The effect of the unique Japanese indication for MitraClip based on left ventricular ejection fraction (LVEF) is unclear. Methods and Results: We analyzed 874 patients who underwent MitraClip because of mitral regurgitation (MR) and compared the characteristics and outcomes between patients with LVEF <30% and ≥30%. Patients with LVEF ≤30% accounted for 33% of the study population and had a higher prevalence of functional MR. Severity of MR after MitraClip was comparable, and LVEF <30% did not independently affect survival. CONCLUSIONS: Japanese unique indication based on LVEF may exclude one third of patients who were treated with MitraClip in Europe.

Chronic phase improvements in electrocardiographic and echocardiographic manifestations of left ventricular hypertrophy after alcohol septal ablation for drug-refractory hypertrophic obstructive cardiomyopathy.

After alcohol septal ablation (ASA), regression of left ventricular hypertrophy (LVH) has been observed in several studies using echocardiography or cardiac magnetic resonance, and favorable changes of myocardial excitation have been expected. However, no studies have focused on the alteration of electrocardiography (ECG) findings after ASA. Therefore, we evaluated serial changes in ECG parameters during the chronic phase after ASA for drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). From 1998 to 2014, we performed 187 ASA procedures in 157 drug-refractory HOCM patients. After excluding patients who underwent dual-chamber pacing therapy and who underwent staged or repeat ASA within 2 years after the index ASA, 25 patients without bundle branch block and additional pacemaker implantation were enrolled in the main study group. ECGs, echocardiograms, and clinical follow-up data were evaluated at baseline and, 1, 6, 12, and 24 months after ASA. Patients with bundle branch block or additional pacemaker implantation were assigned in a referential group (n = 79), in which the echocardiographic changes between baseline and at 1 year were evaluated. Sokolow-Lyon index (SLi), Cornell index, and total 12-lead QRS amplitude significantly decreased during 2-year follow-up after ASA. SLi and Cornell index significantly decreased from 6 to 12 months (p < 0.05 vs. p < 0.01). Changes in SLi were significantly associated with changes in the interventricular septal thickness (r = 0.54, p < 0.005), left ventricular mass index (r = 0.40, p = 0.050), and peak creatine phosphokinase level (r = -0.41, p = 0.042), but not in the Cornell index and 12-lead QRS amplitude. In the comparison between baseline and at 1 year, significant improvements in the interventricular septal thickness, posterior wall thickness, left atrial size, E/A ratio, and E/e' were observed in the echocardiographic study. Changes of SLi reflected regression of LVH after ASA with the best correlation. During the chronic phase after ASA, LVH regression was confirmed by echocardiographic and ECG parameters.

Heart Failure Interventions Targeting Impaired Left Ventricles in Structural Heart Disease.

PURPOSE OF REVIEW: Interventional techniques have been developed for a wide spectrum of mechanisms of heart failure (HF), especially in valvular heart disease and cardiomyopathies (ischaemic cardiomyopathy and hypertrophic cardiomyopathy). In this article, we review recent reports on catheter interventions to treat patients with HF. RECENT FINDINGS: Direct modification using the Parachute device and the REVIVENT-TC device for patients with impaired left ventricle with large infarct scars improves geometry and haemodynamic efficiency, resulting in a reduction of HF symptoms. Interatrial shunt therapy improves symptoms and quality of life in HF patients. Uniquely, left ventricular outflow tract obstruction has also been targeted in patients with transcatheter mitral valve implantation. For advanced stage HF patients with prohibitively high surgical risk, emerging transcatheter interventions make it possible to modify life-limiting symptoms. Further results on HF interventions are expected from ongoing clinical trials.

Relationship of Nonseptal Late Gadolinium Enhancement to Ventricular Tachyarrhythmia in Hypertrophic Cardiomyopathy.

OBJECTIVE: This study aimed to determine the relationship between the extent and the location of late gadolinium enhancement (LGE) and ventricular tachyarrhythmia or implantable cardioverter defibrillator (ICD) in hypertrophic cardiomyopathy (HCM). METHODS: We enrolled 115 patients with HCM and LGE. The location of LGE was divided into septal and nonseptal segments. Clinical backgrounds and LGE were compared in patients between with and without the arrhythmia or consequent ICD installation. RESULTS: There were significant differences in the number of risk markers, left ventricular ejection fraction, extent of global LGE, and extent of nonseptal LGE between the groups (P < 0.01). Multivariate analysis revealed that the number of risk markers and extent of nonseptal LGE contributed to ventricular tachyarrhythmia or ICD installation (P < 0.01). CONCLUSIONS: The nonseptal LGE is related to ventricular tachyarrhythmia or ICD installation. We should be vigilant for nonseptal LGE when applying LGE to risk stratification for HCM.

Time course of the antiplatelet effect after switching to clopidogrel from initial prasugrel therapy in patients with acute coronary syndrome.

Prasugrel is often replaced with clopidogrel after a certain period of time following coronary stenting. However, the time course of platelet aggregation during this replacement is unknown. We performed a prospective, single-arm study to monitor platelet reactivity before and after the replacement. Forty-five patients (mean age 62.6 ± 13 years, 40 male) who received coronary stenting for acute coronary syndrome were initially treated with the loading dose (20 mg) of prasugrel followed by the maintenance dose (3.75 mg/day) for 7 days, then switched to 75 mg/day of clopidogrel. The P2Y12 reaction unit (PRU) level was measured at baseline and selected time points. Prasugrel effectively suppressed PRU from 248 ± 59 at baseline to 145 ± 65 on day 1 (P < 0.001). The PRU value on the final day of prasugrel treatment (day 7) was 156 ± 68 (P < 0.001 vs. baseline). After switching to clopidogrel, PRU was consistently suppressed [146 ± 60, 139 ± 54, and 135 ± 60 on days 9, 11, and 13, respectively (P < 0.001, each point vs. baseline)]. Switching from the initial prasugrel therapy to clopidogrel using the maintenance dose does not cause a drug efficacy gap and stays effective for preventing stent thrombosis.

Different characteristics of cardiac biomarkers to decide and predict the culprit lesions in patients with suspicious acute coronary syndrome.

This multicenter prospective study was conducted to assess high-sensitivity troponin T (hs-TnT) and other biomarkers to decide and predict culprit lesions indicated for emergency percutaneous coronary intervention (PCI) in patients with suspicious acute coronary syndrome (ACS). We have reported Hs-TnT is the most sensitive biomarker for earlier diagnosis and decision making in patients with suspected ACS. In this study, we had conducted subanalysis investigating the usefulness for prediction of ACS culprit lesion. The patients with suspicious ACS and initially negative whole-blood rapid troponin T test, who underwent coronary angiogram (CAG), were enrolled (n = 74). Hs-TnT, quantitative assay for conventional troponin T (c-TnT), creatine kinase MB isozyme (CK-MB), and heart-type fatty acid-binding protein (H-FABP) were simultaneously measured. ACS culprit lesion was described as total occlusion, subtotal occlusion, and/or angiographical unstable lesion such as thrombosis, ulceration or irregularity. The CAG revealed that 49 cases had ACS lesions to be indicated for emergency PCI. The areas under the ROC curves and ROC-optimized cut-off of hs-TnT, c-TnT, CK-MB, and H-FABP were 0.75, 0.67, 0.68, and 0.75, respectively, and 18, 11, 2.0, and 4.6 ng/ml, respectively. In patients with total occlusion and 90-99 % of diameter stenosis (TIMI 2 or 3), hs-TnT could predict emergency PCI with significantly higher sensitivity compared with H-FABP (hs-TnT >14 ng/ml; 71 %, and H-FABP >6.2 ng/dl; 51 %, p = 0.021) and other biomarkers. Meanwhile, H-FABP displayed significant correlations with number of diseased vessels and presence of thrombotic lesion. The present study first revealed different characteristics of correlation between the angiographic culprit lesions and each cardiac biomarker. For prediction of ACS lesions requiring emergency PCI, hs-TnT had the highest sensitivity with satisfied analytical precision.

Distribution and Clinical Significance of High Signal Intensity of the Myocardium on T2-Weighted Images in 2 Phenotypes of Hypertrophic Cardiomyopathy.

OBJECTIVE: The aim of this study was to evaluate distribution and clinical significance of high signal intensity of the myocardium on T2-weighted images (T2-HI) in 2 phenotypes of hypertrophic cardiomyopathy (HCM). METHODS: Thirty-six patients with asymmetrical septal HCM (ASH) and 18 patients with apical HCM (APH) and their 864 myocardial segments were investigated. The distribution of T2-HI was compared with that of late gadolinium enhancement (LGE), and the relationships between T2-HI and clinical risk markers were evaluated. T2 values of the T2-HI were estimated with T2 mapping. RESULTS: The T2-HI was observed in 18 segments (3.1%) in 13 patients with ASH (36.1%) and in 12 segments (4.2%) in 8 patients with APH (44.4%). It was often localized outside LGE. The presence of T2-HI was related to syncope in ASH (P = 0.016). Furthermore, it had higher T2 values (61.1 milliseconds) than the reference myocardium (47.3 milliseconds). CONCLUSIONS: High signal intensity of the myocardium on T2-weighted images often locates outside LGE and reflects myocardial damage, which is related to syncope in ASH.

Magnetic resonance imaging of microvascular obstruction in hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation.

BACKGROUND: The clinical significance of microvascular obstruction (MO) in hypertrophic cardiomyopathy (HOCM) after percutaneous transluminal septal myocardial ablation (PTSMA) remains unknown. PURPOSE: To assess the relationship between the location of MO and the improvement in symptoms and pressure gradient after PTSMA in patients with HOCM. MATERIAL AND METHODS: Twenty-three patients with HOCM underwent MRI within 24 weeks after PTSMA. The MO was defined visually as the hypointense region adjacent to the left or right ventricular cavity, which was surrounded by myocardial infarction. The location of MO and improvement in clinical symptoms and pressure gradient at 3-6 months follow-up were assessed. RESULTS: MO was observed in 16 patients who underwent MRI within 7 weeks after PTSMA. Left-sided MO was observed in 12 patients, and right-sided MO was observed in four patients. Improvement in clinical symptoms and reduction in the pressure gradient were not sufficient in the patients with right-sided MO, while PTSMA was effective in the patients with the left-sided MO. CONCLUSION: The location of MO identified by MRI may be related to the effectiveness of PTSMA at the short-term follow-up. The left-sided MO is related to complete improvement in clinical symptoms and pressure gradients.

Myocardial fibrosis evaluated by Look-Locker and late gadolinium enhancement magnetic resonance imaging in apical hypertrophic cardiomyopathy: association with ventricular tachyarrhythmia and risk factors.

PURPOSE: To evaluate the distribution and extent of myocardial fibrosis identified by either contrast-enhanced Look-Locker or late gadolinium enhancement magnetic resonance imaging (LGE MRI) and their relationships between ventricular tachyarrhythmia or risk factors in apical hypertrophic cardiomyopathy (APH). MATERIALS AND METHODS: Twenty-five APH patients were examined using a 3.0 T or 1.5 T instrument. We used MRI to evaluate myocardial T1 values and scar. We compared the myocardial fibrosis assessed by contrast-enhanced Look-Locker or LGE MRI with ventricular tachyarrhythmia or risk factors for hypertrophic cardiomyopathy. RESULTS: Myocardial scar was present in 17 of the 25 patients with APH. Myocardial scar was distributed predominantly in the apical myocardium (P < 0.01), whereas myocardial T1 values did not differ between the apical, midventricular, and basal septum. The extent of myocardial scar according to 16-segment model and ejection fraction were related to ventricular tachyarrhythmia or risk factors in APH (P < 0.05 for both). The myocardial T1 value was not associated with the tachyarrhythmia or risk factors. CONCLUSION: In APH, the extent of myocardial scar on LGE MRI is associated with ventricular tachyarrhythmia and risk factors. Quantification of the myocardial T1 value is not necessary for its risk stratification.

Delayed enhancement magnetic resonance imaging in hypertrophic cardiomyopathy with Basal septal hypertrophy and preserved ejection fraction: relationship with ventricular tachyarrhythmia.

OBJECTIVE: This study aimed to determine the relationship between delayed enhancement magnetic resonance imaging (DE MRI) and ventricular tachyarrhythmia in patients with hypertrophic cardiomyopathy (HCM) with basal septal hypertrophy and preserved ejection fraction (EF). METHODS: One hundred seven patients with HCM with basal septal hypertrophy and EF greater than 50% underwent cine and DE MRI. Myocardial scar was identified with DE MRI. We assessed whether patient,s background, cine MRI findings, presence of myocardial scar, or number of scarred myocardial segments was related to the occurrence of ventricular tachyarrhythmia. RESULTS: Patient,s age, family history of HCM, and number of scarred segments differed between the patients with and without the arrhythmia. A family history of HCM and number of scarred segments were significantly related to ventricular tachyarrhythmia (P < 0.01). CONCLUSIONS: The number of scarred segments is the significant DE MRI parameter related to ventricular tachyarrhythmia in HCM with basal septal hypertrophy and preserved EF.

Morphological anomalies in obstructive hypertrophic cardiomyopathy: Insights from four-dimensional computed tomography and surgical correlation.

Hypertrophic cardiomyopathy (HCM) is a genetic disorder in which left ventricular outflow tract obstruction critically affects symptoms and prognosis. Traditionally, left ventricular outflow tract obstruction was primarily attributed to septal hypertrophy with systolic anterior motion of the mitral valve. However, recent evidence highlights significant contributions from the mitral valve and papillary muscle anomalies, as well as an apical-basal muscle bundle observed in HCM patients. Accurate morphological assessment is essential when considering septal reduction therapy. While transesophageal echocardiography and cardiac magnetic resonance are recommended for assessing the anomalous structures, four-dimensional computed tomography offers superior spatial resolution and multiplanar reconstruction capabilities. These features enable the evaluation of details of the morphological anomalies, such as the apical-basal muscle band, papillary muscle anomalies, subaortic stenosis, and right ventricular outflow tract obstruction. Based on the detailed assessment of these morphological features, four-dimensional computed tomography has been utilized for planning of surgical correction in a comprehensive HCM center. This approach facilitates the intervention strategies and may improve outcomes in septal reduction therapy for obstructive HCM.

Renin-angiotensin system inhibitors for patients with mild or moderate chronic kidney disease and heart failure with mildly reduced or preserved ejection fraction.

BACKGROUND: Renin-angiotensin system inhibitors (RASI) reduce adverse cardiovascular events in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤40% and mild or moderate chronic kidney disease (CKD). However, RASI administration rate and its association with long-term outcomes in patients with CKD complicated by HF with LVEF >40% remain unclear. METHODS: We analyzed 1923 consecutive patients with LVEF >40% registered within the multicenter database for hospitalized HF. We assessed RASI administration rate and its association with all-cause mortality among patients with mild or moderate CKD (estimated glomerular filtration rate [eGFR]: 30-60 mL/min/1.73 m2). Exploratory subgroups included patients grouped by age (<80, ≥80 years), sex, previous HF hospitalization, B-type natriuretic peptide (higher, lower than median), eGFR (30-44, 45-59 mL/min/1.73 m2), systolic blood pressure (<120, ≥120 mmHg), LVEF (41-49, ≥50%), and mineralocorticoid receptor antagonists (MRA) use. RESULTS: Among patients with LVEF >40%, 980 (51.0%) had mild or moderate CKD (age: 81 [74-86] years; male, 52.6%; hypertension, 69.7%; diabetes, 25.9%), and 370 (37.8%) did not receive RASI. RASI use was associated with hypertension, absence of atrial fibrillation, and MRA use. After multivariable adjustments, RASI use was independently associated with lower all-cause mortality over a 2-year median follow-up (hazard ratio: 0.58, 95% confidence interval: 0.43-0.79, P = 0.001), and the mortality rate difference was predominantly due to cardiac death, consistent in all subgroups. CONCLUSIONS: Approximately one-third of HF patients with mild or moderate CKD and LVEF >40% were discharged without RASI administration and demonstrated relatively guarded outcomes.