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Abstract Background The optimal endovascular treatment (EVT) for chronic total occlusion (CTO) lesions in patients with peripheral artery disease (PAD) has remained unestablished. We encountered a patient with PAD in whom CTO was successfully treated using a novel technique that involved intravascular ultrasound (IVUS) and angled guiding catheter: IVUS Preceding with Angled guiDing catheter (I-PAD) technique. Case presentation A 74-year-old male presented with intermittent claudication attributed to CTO of the right external iliac artery. EVT was performed via the right common femoral artery. We retrogradely advanced the I-PAD system (i.e. partially extending the IVUS transducer portion from the tip of the angled guiding catheter) in the CTO lesion under the real-time guidance of IVUS imaging. We successfully traversed the CTO lesion without the use of a guidewire in approximately three minutes. The procedure concluded successfully without any procedure-related complications, following optimal stenting. Conclusions The I-PAD might be an effective technique to accurately, quickly, and safely pass through CTO lesions.

Abstract Aims Remote dielectric sensing (ReDS) represents a contemporary non‐invasive technique reliant on electromagnetic energy to quantify pulmonary congestion. Its prognostic significance within the context of heart failure (HF) patients remains elusive. This study aimed to assess the prognostic implications of residual pulmonary congestion, as gauged by the ReDS system, among patients admitted due to congestive HF. Methods and results We enrolled hospitalized HF patients who underwent ReDS assessments upon admission and discharge in a blinded manner, independent of attending physicians. We evaluated the prognostic impact of the ReDS ratio between admission and discharge on the primary outcome, which encompassed all‐cause mortality and HF‐related re‐hospitalizations. A cohort of 133 patients (median age 78 [72, 84] years, 78 male [59%]) was included. Over a median observation period of 363 days post‐index discharge, an escalated ReDS group (ReDS ratio > 100%), determined through statistical calculation, emerged as an independent predictor of the primary outcome, exhibiting an adjusted hazard ratio of 4.37 (95% confidence interval 1.13–16.81, P = 0.032). The cumulative incidence of the primary outcome was notably higher in the increased ReDS group compared with the decreased ReDS group (50.1% vs. 8.5%, P = 0.034). Conclusions Elevated ReDS ratios detected during the index hospitalization could serve as a promising prognostic indicator in HF patients admitted for treatment. The clinical ramifications of ReDS‐guided HF management warrant validation in subsequent studies.

Abstract Background Frailty pervades the demographic of individuals afflicted by chronic kidney disease (CKD) and exhibits a robust correlation with a less favorable prognosis. Nonetheless, the evaluation and prognostication of frailty within the incipient stages of dialysis initiation remain shrouded in ambiguity. The necessity arises for an uncomplicated metric that holistically assesses frailty among aged CKD patients, one which lends itself to pragmatic clinical application. Methods In our prospective endeavor, we conducted assessments using the “KIHON checklist (KCL),” a questionnaire comprising 25 points, thoughtfully crafted by the Japanese Ministry of Health, Labour and Welfare to provide a thorough evaluation of the elderly population. This assessment was administered at the commencement of hemodialysis in patients aged 65 years or older. Subsequently, we analyzed the prognostic ramifications of the initial KCL scores on the composite primary endpoint, which encompassed the undesirable outcomes of either being bedridden or succumbing to mortality. Results A total of 24 patients (median age 76 years, 20 men) were included. The median KCL score was 6 [4, 10] points, and it was significantly correlated with the number of components in the revised Japanese Cardiovascular Health Study, which is a diagnostic criterion for frailty (p

Abstract Background Sodium zirconium cyclosilicate (SZC) has recently emerged as a therapeutic option for the management of acute hyperkalemia. Nevertheless, the relative effectiveness, safety, and financial considerations of SZC therapy versus conventional hemodialysis therapy remain uncertain. Methods In this retrospective study, we embarked upon a comparative analysis encompassing the financial aspects, safety profiles, and efficacy metrics associated with SZC therapy and hemodialysis in patients grappling with acute hyperkalemia. No patients had systemic congestion or uremia. Results A total of 21 patients (median 81 years old, 14 men) were included; 14 received SZC therapy and seven underwent hemodialysis. Acute hyperkalemia improved immediately within several days without any procedure-related adverse events, regardless of therapeutic interventions (p

Abstract Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient’s conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e′) (E/e′). Adjusted least-squares mean (LSM) change in E/e′ was − 0.8 (95% confidence interval [CI] − 1.49 to − 0.04) in the azilsartan group and 0.2 (95% CI − 0.49 to 0.94) in the candesartan group, providing the LSM differences of − 1.0 (95% CI − 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was – 2.7 mL/m2 with azilsartan vs 1.4 mL/m2 with candesartan (P = 0.091). The frequency of adverse events related to hypotension and hyperkalemia did not differ between the groups. The current study did not provide strong evidence that azilsartan improves LV diastolic dysfunction, and further confirmatory study is required.

Background: Impaired gastric motility in the form of constipation may often occur in elderly patients with chronic heart failure. Candidates for trans-catheter aortic replacement (TAVR) are of old age and have multiple comorbidities, probably including constipation. However, the clinical implication of a history of constipation in patients receiving TAVR remains unknown. Methods: Patients who underwent TAVR at our large academic center between 2015 and 2022 were eligible. The prognostic impact of the prescribed laxative type and number, which was assumed as the severity of constipation, on the incidence of death or heart failure readmission two years after index discharge was investigated. Results: A total of 344 patients were included. Median age was 85 years, and 99 patients were men. Patients with any laxatives (N = 166) had higher systolic blood pressure, higher plasma B-type natriuretic peptide levels, and a lower prescription rate of renin–angiotensin system inhibitors at the time of index discharge after TAVR (p < 0.05 for all). The number of laxative types was independently associated with the composite primary outcome with an adjusted hazard ratio of 1.83 (95% confidence interval 1.27–2.63, p = 0.001) with a cutoff of one type of laxative used, which significantly stratified the 2-year cumulative incidence of the primary outcome (18% versus 7%, p = 0.001). Conclusions: The presence of constipation was associated with worse clinical outcomes following TAVR. The prognostic impact of an aggressive intervention for constipation remains a future concern in this cohort.

Background: The clinical impact of the withdrawal of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on all-cause readmission in patients with heart failure remains unknown. Methods: We enrolled a total of 212 consecutive patients who were hospitalized for heart failure and received SGLT2i during their index hospitalization between February 2016 and July 2022. Of these patients, 51 terminated SGLT2i during or after their index hospitalization. We evaluated the prognostic impact of the withdrawal of SGLT2i on the primary outcome, which was defined as the all-cause readmission rate/times. Results: Over a median of 23.2 months, all-cause readmission occurred in 38 out of 51 patients (74.5%) withdrawn from SGLT2i and 93 out of 161 patients (57.8%) with continuation of SGLT2i (p = 0.099). The incidence of all-cause readmissions per year was 0.97 [0–1.50] in patients withdrawn from SGLT2i and 0.50 [0–1.03] in patients with continuation of SGLT2i (p = 0.030). There was no significant difference in total medical costs (62,906 [502–187,246] versus 29,236 [7920–180,305] JPY per month, p = 0.866) between both patient groups. Conclusions: Termination of SGLT2i may be associated with incremental all-cause readmission and no benefit in reducing total medical costs.

Background: Remote dielectric sensing (ReDS) systems can estimate the amount of lung fluid non-invasively and easily without expert techniques. The correlation between the elevated ReDS value and other modalities that estimate pulmonary congestion has been validated. The clinical implications of lower ReDS values, which may indicate hypovolemia, remain unknown. Methods: A total of 138 patients who were hospitalized for various cardiovascular-related problems and underwent ReDS value measurements at the index discharge in a blinded manner to the attending clinicians were eligible for inclusion. Patients with ReDS values > 30%, indicating the presence of pulmonary congestion, were excluded. The prognostic impact of lower ReDS values on all-cause readmission after index discharge was evaluated. Results: A total of 97 patients were included. The median age was 78 years, and 48 were men. The median ReDS value at index discharge was 26% (23%, 27%). A lower ReDS value correlated with smaller inferior vena cava maximum diameters (r = 0.46, p < 0.001) and higher blood urea nitrogen/creatinine ratios (r = −0.35, p < 0.001). A lower ReDS value (≤25%) was associated with a risk of all-cause readmissions with an unadjusted hazard ratio of 2.68 (95% confidence interval 1.09–6.59, p = 0.031) and an adjusted hazard ratio of 2.30 (95% confidence interval 0.92–5.78, p = 0.076). Its calculated cutoff of 25% significantly stratified the cumulative incidence of the primary outcome (36% versus 17%, p = 0.038). Conclusions: A lower ReDS value may indicate hypovolemia and be associated with the risk of all-cause readmission in patients hospitalized for cardiovascular diseases.

Background: Remote dielectric sensing (ReDS) systems can quantify the degree of pulmonary congestion rapidly and non-invasively. However, the clinical implications of ReDS-guided medication adjustment remain uncertain. Methods: Patients hospitalized to treat cardiovascular diseases, including heart failure, valvular disease, and coronary artery disease, and underwent ReDS measurement before index discharge between 2021 and 2022 were included. According to our institutional protocol, ReDS values were blinded to the attending clinicians until February 2022 (blind period). After the period, ReDS values were timely opened to the attending clinicians, and medications such as diuretics were adjusted according to the ReDS values (target value between 20% and 35%) before index discharge (open period). A composite primary outcome of all-cause death and heart failure readmissions was compared between the two groups. Results: A total of 183 patients were included (median 79 years old, 101 men), consisting of 138 patients in the blind period and 45 patients in the open period. During a median of 646 (401, 818) days after the index discharge, 33 patients experienced the primary outcome of interest. Management during the open period, where medications were adjusted according to ReDS values, was independently associated with a lower incidence of the primary outcome with an adjusted hazard ratio of 0.22 (95% confidence interval 0.05–0.94, p = 0.041), as compared with those of the blind period. Conclusions: According to the findings of the present retrospective study, ReDS-guided management may have the potential to reduce the risk of mortality and heart failure admission in individuals hospitalized for cardiovascular diagnoses. Further prospective randomized control trials involving those with a variety of background etiologies and clinical scenarios are warranted to validate our findings and establish optimal ReDS-guided management.

Background: Although the dynamic changes of atrial natriuretic peptide (ANP) expressions in a failing heart are well-documented, the clinical implications of detailed measurements of each ANP molecular form processed from proANP remain unclear. Methods: Patients screening was conducted on patients who were eligible for cardiac resynchronization therapy (CRT) between 2014 and 2019 in our institution. Blood samples and echocardiographic parameters were collected on the day before and six months after implantation. Total ANP, proANP, and N-terminal fragment of proANP (NT-proANP) were examined as predictive biomarkers for cardiac death, left ventricular assist device implantation, and heart failure hospitalization following CRT implantation. Results: A total of 86 subjects (mean age 70 years, 64 males) who underwent successful CRT implantation were enrolled. Plasma levels of total ANP, proANP, and NT-proANP were not normally distributed [25.8 pM (interquartile range: 11.1–53.1), 2.2 pM (1.0–5.4), and 4.1 nM (2.4–7.1), respectively]. Over a median follow-up of 2.7 years, 31 patients (2 deaths and 29 heart failure hospitalizations) reached the endpoints. Among the different ANP forms, only NT-proANP emerged as an independent predictor of the composite outcome (adjusted odds ratio of 2.542 in those with levels above vs. below the median, 95 % confidence interval 1.151–5.615, p = 0.021). NT-proANP levels were associated with left atrial volume and left diastolic functional parameters and decreased in response to echocardiographic improvements at six months post-implantation (16 ± 44 % decrease in responders vs 18 ± 60 % increase in non-responders, p = 0.005). Conclusion: Pre-implantation NT-proANP levels could serve as a predictive factor for clinical outcomes in recipients of CRT.

Abstract Background Oxidative stress is associated with atrial fibrillation recurrence following catheter ablation. Urinary isoxanthopterin (U‐IXP) is one of the noninvasive markers which reflect the reactive oxygen species; however, its ability to predict atrial tachyarrhythmias (ATAs) occurrence following catheter ablation remains uncertain. Methods Among the patients who received scheduled catheter ablation for atrial fibrillation, baseline U‐IXP levels were measured just before the procedure. The prognostic impact of baseline U‐IXP upon postprocedural ATAs occurrence was investigated. Results Among 107 patients (71 years old, 68% men), baseline U‐IXP level was 0.33 nmol/gCr on the median. During a mean of 603 days of follow‐up, 32 patients had ATAs. Baseline higher U‐IXP was independently associated with the occurrence of ATAs following catheter ablation with a hazard ratio of 4.69 (95% confidence interval: 1.82–12.37, p = .001) adjusted for the left atrial diameter, a persistent type, and hypertension which were potential confounders, with a cutoff of 0.46 nmol/gCr, which stratified cumulative incidence of ATAs occurrence ( p

Background: Significant pericardial effusion requires percutaneous drainage. Some patients experience recurrent pericardial effusion following index drainage, but its risk factors remain unknown. Such knowledge should further improve the clinical management of individuals presenting with pericardial effusion for risk stratification and the construction of therapeutic and management strategies beforehand. Methods: Patients who underwent percutaneous drainage for pericardial effusion between 2018 and 2023 were retrospectively included and were followed for 2 years or until November 2023. Baseline factors associated with recurrent pericardial effusion that required percutaneous drainage again were investigated to identify the high-risk cohort. Results: A total of 39 patients (83 years on median, 28 males) were included. During the 2-year observation period, 11 patients had the primary outcome. The left ventricular end-diastolic diameter at baseline was independently associated with the primary outcome with an adjusted hazard ratio of 0.88 (95% confidence interval 0.80–0.97, p = 0.013) with a cutoff of 42 mm, which significantly stratified the cumulative incidence of the primary outcome (53% versus 10%, p = 0.011). Conclusions: Recurrent pericardial effusion after percutaneous drainage is not a rare phenomenon. A smaller left ventricular endo-diastolic diameter was an independent risk factor for recurrent pericardial effusion. The clinical implications of our findings in daily clinical practice should be validated in future prospective studies. Further studies are warranted to clarify the underlying causality between them.

Background: Transcatheter edge-to-edge mitral valve repair (TEER) has emerged as a viable approach to addressing substantial secondary mitral regurgitation. In the contemporary landscape where ultimate heart failure-specific therapies, such as cardiac replacement modalities, are available, prognosticating a high-risk cohort susceptible to early cardiac mortality post-TEER is pivotal for formulating an effective therapeutic regimen. Methods: Our study encompassed individuals with secondary mitral regurgitation and chronic heart failure enlisted in the multi-center (Optimized CathEter vAlvular iNtervention (OCEAN)-Mitral registry. We conducted an assessment of baseline variables associated with cardiac death within one year following TEER. Results: Amongst the 1517 patients (median age: 78 years, 899 males), 101 experienced cardiac mortality during the 1-year observation period after undergoing TEER. Notably, a history of heart failure-related admissions within the preceding year, utilization of intravenous inotropes, and elevated plasma B-type natriuretic peptide levels emerged as independent prognosticators for the primary outcome (p < 0.05 for all). Subsequently, we devised a novel risk-scoring system encompassing these variables, which significantly stratified the cumulative incidence of the 1-year primary outcome (16%, 8%, and 4%, p < 0.001). Conclusions: Our study culminated in the development of a new risk-scoring system aimed at predicting 1-year cardiac mortality post-TEER.

Abstract Background Xanthine oxidase activity has a key role in the development of oxidative stress and progression of cardiovascular diseases. However, the change of xanthine oxidase activity following hemodialysis and its prognostic impact remain uncertain. Methods We prospectively included hemodialysis patients who did not take any anti-hyperuricemic agents and measured their xanthine oxidase activity before and after the index hemodialysis. The impact of change in xanthine oxidase activity during hemodialysis on cardiovascular death were investigated. Results A total of 46 patients (median 72 years old, 29 men) were included. During hemodialysis, a common logarithm of xanthine oxidase activity decreased significantly from 1.16 (0.94, 1.27) to 1.03 (0.80, 1.20) (p

Background: The safety and efficacy of atrial fibrillation (AF) ablation in individuals with heart failure (HF) with preserved ejection fraction (EF), particularly concerning the occurrence of post-procedural adverse events necessitating hospitalization, including anticoagulant-associated major bleeding, still lack conclusive determination. Methods: Data from patients with HF and AF who underwent catheter ablation for AF between 2019 and 2022 at our institution were retrospectively reviewed. All participants were divided into an EF < 50% group or an EF ≥ 50% group according to their baseline left ventricular EF. The composite incidence of the clinical events following catheter ablation was compared between the two groups: (1) all-cause death, (2) HF hospitalization, (3) stroke or systemic embolism, and (4) major bleeding. Results: A total of 122 patients (75 years old, 68 male) were included. Of them, 62 (50.8%) patients had an EF ≥ 50%. EF ≥ 50% was an independent predictor of the composite endpoint (adjusted odds ratio 6.07, 95% confidence interval 1.37–26.99, p = 0.018). The incidences of each adverse event were not significantly different between the two groups, except for a higher incidence of major bleeding in the EF ≥ 50% group (12.7% vs. 0%, p = 0.026). Conclusions: Among patients with HF coupled with AF, the incidence of adverse events following AF ablation proved notably elevated in patients with EF ≥ 50% in contrast to their counterparts with EF < 50%. This disparity primarily stems from a heightened occurrence of major bleeding within the EF ≥ 50% cohort. The strategy to reduce adverse events, especially in patients with EF ≥ 50%, remains the next concern.

Background: The optimal criteria for patient selection in the context of adaptive servo-ventilation (ASV) therapy remain a subject of ongoing investigation. We postulate that baseline plasma volume, assessable through several straightforward clinical parameters, might be correlated with a more pronounced reduction in plasma B-type natriuretic peptide (BNP) levels following mid-term ASV therapy. Methods: We included patients diagnosed with congestive heart failure who had received continuous ASV therapy for a minimum of three months. The primary outcome of interest was the extent of decline in logarithmically transformed plasma BNP levels, defined as a decrease of more than 0.10 during the 3-month ASV treatment period. Results: A total of 66 patients were included in the study. The median age of the cohort was 66 years, with 53 patients (80%) being male. The median plasma volume status at baseline was −16.9%, and patients were categorized into two groups based on this median value. Patients with elevated baseline plasma volume status experienced a statistically significant reduction in plasma BNP levels (p = 0.016), whereas those with lower plasma volume exhibited no significant change in BNP levels (p = 0.23). A higher baseline plasma volume status was independently associated with a significant reduction in plasma BNP levels, with an adjusted odds ratio of 1.036 (95% confidence interval: 1.01–1.07, p = 0.032). Conclusions: The presence of systemic congestion at baseline, quantified by the estimated plasma volume status, may serve as a crucial determinant of the efficacy of ASV therapy, leading to improvements in plasma BNP levels among patients suffering from congestive heart failure.

Background: Tolvaptan sodium phosphate (Samtas®; Otsuka Pharmaceutical, Tokyo, Japan) is a novel intravenous aquaretic diuretic aimed at individuals experiencing advanced congestion refractory to conventional diuretics and having difficulty with oral intake. Despite its potential, the true efficacy and practicality of this compound within real-world clinical settings remain obscure. Methods: A retrospective analysis of clinical data was conducted, examining trends among consecutive in-hospital patients diagnosed with congestive heart failure who underwent treatment with tolvaptan sodium phosphate at a prominent academic medical center between June 2022 and June 2023. Results: Twenty-one patients were enrolled (median age: 75 years, serum N-terminal pro B-type natriuretic peptide: 8941 pg/mL). Among them, 14 patients (67%) received non-invasive/invasive positive-pressure ventilation, and 17 patients (81%) concurrently received intravenous inotropes. Subsequent to the initiation of tolvaptan sodium phosphate treatment, a significant increase in urine volume was observed on the following day (p = 0.036). Urine osmolality decreased from 356 (318, 443) at baseline to 247 (176, 333) mOsm/kg after 4 h (p = 0.002). No occurrences of hypernatremia were recorded during the therapeutic period. Notably, two patients transitioned from tolvaptan sodium phosphate treatment to continuous hemodiafiltration due to insufficient efficacy. Conclusions: In routine clinical practice, intravenous tolvaptan sodium phosphate exhibits potential efficacy and practicability in the majority of congestive heart failure patients exhibiting refractory congestion, unstable hemodynamics, and challenges with oral intake.

Background: Transcatheter atrial septal closures for secundum atrial septal defects (ASD) have demonstrated favorable clinical outcomes. However, the impact of device implantation on the stiffness of the left atrium remains unclear. Method: Patients with secundum ASD undergoing transcatheter closure and follow-up right heart catheterization at six months were included. We investigated the relationship between post-procedural (E/e’ ratio)/(LAs strain) ratio, an index of left atrial stiffness, and baseline characteristics, including echocardiographic and hemodynamic parameters. Results: Forty patients were included (median 69 (56, 75) years, 12 men, and pulmonary systemic flow ratio 2.27 (1.96, 2.86)). Trans-catheter ASD closure was successfully performed without any major complications, accompanying a significant reduction in right ventricular to left ventricular size ratio from 1.04 (0.87, 1.13) to 0.74 (0.66, 0.86) (p < 0.01). The (E/e’ ratio)/(LAs strain) ratio was markedly elevated the day after the procedure and was further increased 6 months later (before: 0.25 (0.17, 0.34), 1 day later: 0.34 (0.27, 0.50), 6 months later: 0.43 (0.27, 0.76), p < 0.01). The groups with higher (E/e’ ratio)/(LAs strain) ratios at 6 months had significantly more severe heart failure conditions including lower cardiac output and higher plasma B-type natriuretic peptides. Conclusions: Patients undergoing transcatheter ASD closure experienced improvement in hemodynamics and clinical symptoms but an elevation in left atrial stiffness post-procedure. The clinical ramifications of this finding, particularly during the longer-term observation period subsequent to ASD closure, warrant further investigation.

Background: Ivabradine reduces heart rate by inhibiting the “funny current” expressed on the sinoatrial node and improves mortality and morbidity in patients with systolic heart failure and sinus tachycardia. The funny current is known to be expressed also on the atrioventricular node according to experimental studies. However, the impact of ivabradine on PR interval remained unknown. Methods: Patients with a left ventricular ejection fraction of less than 50% who received 1 month of ivabradine were screened. Electrocardiographic and echocardiographic data, particularly concerning heart rate, the PR interval, and trans-mitral flow pattern, were collected at baseline and 1-month follow-up. The primary endpoint was defined as the composite of cardiovascular death and hospital readmission for worsening heart failure following ivabradine administration. Results: In the cohort of 29 enrolled patients (median age: 66 years, 62% male), the median baseline heart rate was 86 beats per minute and the median PR interval was 168 milliseconds. Following ivabradine administration, a significant decrease of 20 beats per minute in the heart rate and a significant increase of 24 milliseconds in the PR interval were observed. The truncated interval of the A-wave, detected in the trans-mitral flow, consistently demonstrated a negative correlation with the PR interval both before and after the administration of ivabradine. During a median of 1.8 years of follow-up, six patients reached the primary endpoint. A combination of heart rate reduction and PR prolongation following ivabradine administration, both of which were independent factors associated with the primary endpoint (p < 0.05 for both), was associated with greater freedom from the primary endpoint compared with either/neither of them (p = 0.002). Conclusions: Ivabradine seems to prolong PR interval, which is a novel surrogate marker of favorable clinical outcomes in patients with systolic heart failure. This effect may be associated with the dynamics of the trans-mitral flow pattern, in conjunction with heart rate and the PR interval. Clinical implications of PR interval-guided ivabradine therapy remains the future concern.

Background: A recently proposed mechanism, the intestinal–cardiovascular relationship, serves as a framework to elucidate the interplay between these two systems. In our investigation, we assessed the prognostic implications of colon wall thickness, a marker correlated with intestinal congestion and dysfunction, in patients diagnosed with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). Methods: Patients diagnosed with severe aortic stenosis who underwent TAVR at our institution during the period spanning 2015 to 2022 were retrospectively enrolled. As part of the institutional protocol, patients underwent abdominal computed tomography upon admission, preceding TAVR. Our analysis aimed to assess the influence of colon wall thickness on the occurrence of either all-cause mortality or readmission due to heart failure within a two-year period. Results: A total of 345 patients were included. The median age was 85 (82, 88) years, and 99 patients were male. Baseline colon wall thickness was distributed widely, with a median value of 2.2 (2.0, 2.5) mm. Patients with thicker colon walls tended to have lower pulmonary artery pulsatility index values, indicating more impaired right ventricular function and more advanced malnutrition. A thicker colon wall was independently associated with 2-year death or heart failure readmission with a hazard ratio of 2.02 (95% confidence interval 1.01–14.07), adjusted for hemoglobin, age, and plasma B-type natriuretic peptide levels (p = 0.049), and significantly stratified the primary endpoint at a cutoff of 2.7 mm (25% versus 10%, p = 0.005). Conclusions: Our initial observation revealed that a thicker baseline colon wall correlated with increased rates of mid-term mortality and readmission due to heart failure subsequent to TAVR. Developing a comprehensive understanding of the underlying causality necessitates further in-depth investigations through subsequent studies.

Background: Small dense LDL-cholesterol is a recently discovered cardiovascular risk factor beyond LDL-cholesterol. Pemafibrate is a novel selective peroxisome proliferator-activated receptor-α modulator that reduces triglyceride levels. Given the significant association between triglycerides and small dense LDL-cholesterol levels, pemafibrate may reduce the levels of small dense LDL-cholesterol. Methods: Patients with hypertriglyceridemia who started pemafibrate therapy and continued it for >3 months between 2018 and 2022 were included in this retrospective study. The levels of small dense LDL-cholesterol, which was estimated using Sampson’s equation, consisting of the LDL-cholesterol and triglyceride levels, were compared between baseline and 3-month follow-up. Results: A total of 98 patients receiving pemafibrate therapy (median age: 63 years, 69 male) were eligible, including 33 patients (34%) who received concomitant statins. Small dense LDL-cholesterol levels decreased significantly during the course of 3-month pemafibrate therapy from 48.9 (IQR: 35.7, 57.9) mg/dL to 38.8 (IQR: 30.0, 45.1) mg/dL, regardless of the concomitant administration of statins (p < 0.001). The rate of cardiovascular events decreased significantly from the pre-treatment 1-year period to the treatment 1-year period (from 13 to 2 events, from 0.133 to 0.021 events per year, incidence rate ratio: 0.16, 95% confidence interval: 0.14–0.17, p < 0.001). Conclusions: Pemafibrate therapy may mitigate the concentrations of small dense LDL-cholesterol autonomously in patients manifesting hypertriglyceridemia within the authentic clinical milieu. The clinical importance of the diminishment in small dense LDL-cholesterol instigated via pemafibrate merits further scrutiny.

Background: The spleen seems to be a significant buffer of the effective circulating blood volume by changing its size dramatically according to hemodynamics. The cardio–splenic relationship has been recently proposed in the literature regarding heart failure cohorts, and the splenic size has been proposed as a prognostic factor in these cohorts. However, the clinical implication of the splenic size in patients receiving trans-catheter aortic valve replacement (TAVR) remains unknown. Methods: Patients who underwent TAVR at our institute between 2015 and 2022 were eligible. Of these, the patients whose abdominal computed tomography imaging was obtained before TAVR were included. The volume of the spleen was measured in all the participants. The prognostic impact of the indexed splenic volume (SVI) on the 2-year cardiac death or heart failure readmissions was evaluated. Results: A total of 343 patients (86 years, 98 males) were included. The median value of the peak velocity at the aortic valve was 4.4 (4.0, 4.8) m/s and the median SVI was 65.5 (48.9, 86.9) mL/m2. A lower SVI tended to be associated with a lower cardiac output, whereas a higher SVI was associated with a higher plasma volume. The SVI was independently associated with the 2-year cardiac death or heart failure readmission after TAVR with a hazard ratio of 1.09 (95% confidence interval 1.01–1.18, p = 0.041), adjusted for potential confounders. A calculated cutoff of SVI was 70.2 mL/m2, which significantly stratified the cumulative incidence of the primary outcome (10% versus 4%, p = 0.033). Conclusion: A high baseline SVI, which was associated with systemic congestion, was associated with a higher incidence of cardiac death or heart failure readmission after TAVR. Further studies are warranted to clarify the detailed cardio–splenic relationship and implication of measuring the SVI in this cohort.

Background: Individuals with heart failure displaying supra-normal left ventricular ejection fraction (snLVEF) may exhibit less favorable clinical outcomes in contrast to their counterparts with normal left ventricular ejection fraction (nLVEF). The distinctive characteristics and mid-term prognosis of individuals with severe aortic stenosis and snLVEF following transcatheter aortic valve replacement (TAVR) remain enigmatic. Methods: Among 7393 patients diagnosed with severe aortic stenosis who underwent TAVR between 2013 and 2019 and were enlisted in the optimized transcatheter valvular intervention (OCEAN-TAVI) multicenter registry (UMIN000020423), we selected patients with left ventricular ejection fraction (LVEF) ≥ 50%. snLVEF was defined as LVEF exceeding 65%. We compared the baseline characteristics and assessed three-year post-TAVR mortality and heart failure readmission rates between the snLVEF (LVEF > 65%) and nLVEF cohorts (LVER 50–65%). Results: Our study cohort comprised 5989 patients (mean age 84.4 ± 5.1 years and 1783 males). Among these, 2819 patients were categorized within the snLVEF cohort, while the remaining 3170 were allocated to the nLVEF group. Individuals within the snLVEF cohort were more likely to be female and displayed lower levels of natriuretic peptides, as well as smaller left ventricular dimensions in comparison to their nLVEF counterparts (p < 0.05 for all). The presence of snLVEF emerged as an independent predictor of the three-year composite endpoint relative to nLVEF, with an adjusted hazard ratio of 1.16 (95% confidence interval 1.02–1.31, p = 0.023) after accounting for several potential confounding factors. Conclusions: snLVEF was relatively common among candidates for TAVR with preserved ejection fraction. Patients harboring snLVEF appear to manifest a distinctive clinical profile and encounter less favorable clinical outcomes following TAVR in contrast to those characterized by nLVEF.

Abstract Aims/Introduction Diastolic cardiac dysfunction in type 2 diabetes (DD2D) is a critical risk of heart failure with preserved ejection fraction. However, there is no established biomarker to detect DD2D. We aimed to investigate the predictive impact of fragmented QRS (fQRS) on electrocardiography on the existence of DD2D. Materials and Methods We included in‐hospital patients with type 2 diabetes without heart failure symptoms who were admitted to our institution for glycemic management between November 2017 and April 2021. An fQRS was defined as an additional R′ wave or notching/splitting of the S wave in two contiguous electrocardiography leads. DD2D was diagnosed according to the latest guidelines of the American Society of Echocardiography. Results Of 320 participants, 122 patients (38.1%) had fQRS. DD2D was diagnosed in 82 (25.6%). An fQRS was significantly associated with the existence of DD2D (odds ratio 4.37, 95% confidence interval 2.33–8.20; p

(1) Background: Constipation is one of the most serious adverse effects of potassium-lowering agents and decreases patients’ quality of life. Sodium zirconium cyclosilicate (SZC) is a recently innovated potassium binder intended for patients with hyperkalemia. The impact of SZC on the worsening of constipation, as compared with conventional potassium binders, remains unknown. (2) Methods: Patients with hyperkalemia who continued SZC for over 3 months between July 2020 and May 2022 were included in this retrospective study. Patients who received other conventional potassium binders during the same period were included as a control group. Trends in the doses of anti-constipation agents during the 3-month therapeutic period were compared between the two groups as a surrogate for worsening constipation. (3) Results: A total of 50 patients (median age 74 years, 31 male) were included, consisting of 22 patients with SZC and 28 patients with other conventional potassium binders. All patients had hyperkalemia and chronic kidney disease at baseline. During the 3-month therapeutic period, serum potassium levels decreased significantly in both groups (p < 0.05 for both). The number of anti-constipation remained unchanged in the SZC group but tended to increase in the control group (p = 0.56 and p = 0.090, respectively). The total dose change in all anti-constipations was significantly lower in the SZC group than in the control group (p = 0.037). (4) Conclusions: Conventional potassium binders have a tendency to worsen constipation, whereas SZC may have the potential to improve hyperkalemia without worsening constipation. SZC may be recommended, particularly in elderly patients with ongoing or high-risk constipation.

Background: Percutaneous left atrial appendage occlusion (LAAO) therapy using the WATCHMAN system has been introduced to prevent thrombosis and minimize the use of anticoagulants in patients with non-valvular atrial fibrillation. Given the high risk of bleeding and stroke in elderly patients, these patients would be good candidates for this therapy. However, the efficacy and feasibility of LAAO therapy in elderly patients remains uncertain. Methods: Consecutive patients who underwent LAAO therapy using the WATCHMAN system in a large academic center between June 2020 and March 2023 were included. The safety and efficacy of LAAO therapy during the 1-year observation period in patients aged ≥85 years old were compared with those in the younger cohort. Results: A total of 188 patients (78.4 ± 6.9 years old, 133 male patients) were included. 34 patients were ≥85 years old, 96 were between 75 and 84 years old, and 58 were 2DS2-VASc score and were at greater risk of falling-related bleeding compared with the younger cohort. The device implantations were successful in all patients except for one. During the 1-year observation period, one patient had a peri-device leak >5 mm and there were 6 device-related cases of thrombosis, whose incidence was not significantly different between the groups (p = 0.98). The cumulative incidences of bleeding and thrombotic events in the elderly group were as low as in the younger cohort (p > 0.05 for both). Most anticoagulants were terminated regardless of age. Conclusion: The mid-term feasibility and efficacy of percutaneous LAAO therapy using the WATCHMAN system in elderly patients aged ≥85 years were as acceptable as in the younger cohort.

Background: H2FPEF is a recently introduced score for the diagnosis of heart failure with preserved ejection fraction (HFpEF). Many patients with severe aortic stenosis have clinical/subclinical HFpEF and have worsening heart failure even after trans-catheter aortic valve replacement (TAVR). We investigated the prognostic impact of the H2FPEF score in TAVR candidates. Methods: Patients undergoing TAVR procedures at a single academic center between 2015 and 2022 were included. The H2FPEF score was calculated using baseline characteristics before TAVR. The prognostic impact of the score on the post-TAVR composite endpoint, consisting of all-cause death and heart failure readmissions during the 2-year observation period, was evaluated. Results: A total of 244 patients (median age 86 years, 70 males) were included. The median value of H2FPEF score was 3 (2, 4). The score was significantly associated with the primary outcome with a hazard ratio of 1.33 (95% confidence interval 1.02–1.74, p = 0.036). We constructed a modified H2FPEF score by adjusting cutoffs of several items for better prognostic stratification (i.e., age and body mass index). A modified score had a higher area under the curve than the original one (0.65 vs. 0.59, p = 0.028) and was independently associated with the primary outcome with an adjusted hazard ratio of 1.22 (95% confidence interval 1.01–1.49, p = 0.047). Conclusions: A modified H2FPEF score, which was originally developed to diagnose the presence of HFpEF, could be used to risk-stratify elderly patients receiving TAVR. The clinical utility of this score should be validated in future studies.

The combination of sacubitril and valsartan has recently become eligible for reimbursement in Japan for the treatment of hypertension. However, the real-world clinical efficacy of sacubitril/valsartan in patients with hypertension who are taking multiple anti-hypertensive medications remains to be characterized. We treated a man in his late 40s who had undergone a percutaneous coronary intervention and had hypertension that was refractory to multiple anti-hypertensive medications. We initiated sacubitril/valsartan 200 mg/day as an add-on therapy, and 3 months later, his blood pressure had decreased from 154/78 mmHg to 134/70 mmHg, in the absence of any drug-related adverse events. Furthermore, his left ventricular mass index had improved from 135 g/m 2 to 112 g/m 2 . Thus, sacubitril/valsartan might ameliorate hypertrophy in patients with hypertension.

Background: Recent clinical trials have demonstrated that tafamidis (Pfizer Inc., New York, NY, USA) reduced all-cause mortality and the number of cardiovascular hospitalizations compared with placebo in patients with transthyretin cardiac amyloidosis. However, the optimal surrogate markers during tafamidis treatment remain unknown. Methods: Consecutive patients with transthyretin cardiac amyloidosis who received tafamidis in our institute between May 2019 and December 2022 were retrospectively evaluated. The prognostic impact of an increase in troponin I levels during tafamidis therapy was evaluated. Results: A total of 18 patients (median age 77 years, 84% male) were included. For 14-month tafamidis therapy on median, cardiac troponin I levels increased in five patients. The cumulative incidence of all-cause hospitalization was significantly higher in the troponin-increased group than in the others (100% versus 33%, p < 0.0001). Troponin increase was independently associated with the cumulative incidence of all-cause hospitalization with an adjusted hazard ratio of 5.14 (95% confidence interval 1.02–25.9, p = 0.048). Conclusions: The increase in cardiac troponin levels may be a reasonable surrogate marker of response to tafamidis therapy in patients with transthyretin cardiac amyloidosis.

Background and Objectives: Sex-specific outcome in patients with acute myocardial infarction-related cardiogenic shock (AMI-CS) receiving temporary mechanical circulatory support remains controversial. Materials and Methods: Patients with AMI-CS who received Impella support were prospectively enrolled in the Japanese registry for Percutaneous Ventricular Assist Device. Patients enrolled between January 2021 and December 2022 were considered to be eligible. Patients with out-of-hospital cardiac arrest and those without revascularization were excluded. The sex disparity in the 30-day survival after the initiation of Impella support was evaluated. Results: A total of 924 patients (median age 73 years; 21% female) were included. Female patients were older and had a smaller physiques than male patients (p < 0.05 for both). Female sex was significantly associated with a higher 30-day mortality after adjustment for four other potential confounders with a hazard ratio of 1.365 (95% confidence interval 1.026–1.816, p = 0.0324). In the female cohort, patients who received Impella prior to revascularization (N = 138) had a greater survival rate compared to those who received Impella after revascularization (68.1% versus 44.8%, p = 0.0015). Conclusions: Among the patients with AMI-CS who received Impella support and underwent revascularization, female sex was independently associated with a lower 30-day survival. For female patients, early initiation of Impella support prior to revascularization may improve their clinical outcomes.

Background: Vericiguat, a novel oral soluble guanylate cyclase stimulator, decreased the incidence of cardiovascular death and heart failure hospitalization in the cohort receiving triple therapy for heart failure with reduced ejection fraction. However, efficacy and optimal patient selection in real-world practice in the era of “quadruple therapy” remains unknown. Methods: Consecutive patients who received vericiguat between September 2021 and December 2022 were retrospectively evaluated. Results: A total of 28 patients (median age 66 years, median left ventricular ejection fraction 33%) were included. Of them, 21 patients (75%) received quadruple therapy, and the dose of sacubitril/valsartan was 100 mg in the median. Three patients receiving dobutamine infusion discontinued vericiguat due to symptomatic hypotension. One patient with a high N-terminal pro-B-type natriuretic peptide of 4848 pg/mL at the baseline underwent unexpected heart failure hospitalization. Efficacy was evaluated in 21 patients who continued vericiguat for more than 4 months. The plasma B-type natriuretic peptide concentration tended to increase during the six-month pre-treatment period from 104 pg/mL to 179 pg/mL on median (p = 0.665) but remained unchanged after six-month vericiguat treatment to 170 pg/mL on median (p = 0.188). Conclusions: Vericiguat therapy might be feasible and effective upon quadruple therapy for those with heart failure, although further investigation is warranted to validate our findings.

Background: The remote dielectric sensing (ReDS) system is a recently introduced non-invasive technology used to easily estimate the degree of lung fluid volume without any expert techniques. In the previous literature, ReDS values had a moderate correlation with invasively measured pulmonary artery wedge pressure (PAWP), the gold standard for representing left heart preload. Considering the mechanism of ReDS technology, ReDS values may be inappropriately elevated in the presence of pleural effusion (PE), and the ability of the ReDS system to estimate PAWP may decrease in such a situation. Methods: In-hospital patients with cardiovascular diseases underwent computed tomography, and the presence of pleural effusion (PE) was evaluated. The measurement of ReDS values using the ReDS system and the measurement of PAWP using invasive right heart catheterization were also performed simultaneously. The impact of the presence of PE on the relationship between the ReDS values and PAWP was evaluated. Results: A total of 59 patients (79 years, 30 male) were included. The median ReDS value was 25% (IQR: 22%, 30%) and the median PAWP level was 13 (IQR: 10, 18) mmHg. Of these patients, 11 had PE. PAWP was not significantly different between the two groups, whereas the ReDS values in the PE group were significantly higher than in the no-PE group. The impact of the presence of PE on the ReDS values was significant, with a beta value of 6.61 (95% confidence interval: 4.80–8.42, p < 0.001) upon adjusting for the levels of PAWP. Conclusions: We should pay attention to interpreting ReDS values when assessing the degree of pulmonary congestion in patients with PE, because ReDS values may be inappropriately elevated in this cohort.

Background: Psoas muscle mass is a recently featured index of sarcopenia, which has a negative prognostic impact in patients with a variety of diseases. We investigated the prognostic impact of baseline psoas muscle mass in patients receiving a trans-catheter aortic valve replacement (TAVR). Methods: Patients who received TAVR at our center between 2015 and 2022 were included. Patients received computer tomography imaging upon admission as an institutional protocol, and psoas muscle mass was measured, which was indexed by body surface area. Patients were followed for four years or until January 2023. The prognostic impact of psoas muscle mass index on 4-year mortality following index discharge was evaluated. Results: A total of 322 patients (85 years, 95 male) were included. Median psoas muscle mass index at baseline was 10.9 (9.0, 13.5) × 10 cm3/m2. A lower psoas muscle mass index tended to be associated with several index of malnutrition and sarcopenia. A psoas muscle mass index was independently associated with 4-year mortality with an adjusted hazard ratio of 0.88 (95% confidence interval 0.79–0.99, p = 0.044). Patients with lower psoas muscle mass index (below the statistically calculated cutoff of 10.7 × 10 cm3/m2, N = 152) had significantly higher cumulative 4-year mortality compared with others (32% versus 13%, p = 0.008). Conclusions: A lower psoas muscle mass index, which is a recently featured objective marker of sarcopenia, was associated with mid-term mortality following TAVR in the elderly cohort with severe aortic stenosis. The measurement of psoas muscle mass index prior to TAVR could have clinical implications for shared decision-making among patients, their relatives, and clinicians.

Background: Morbidity and mortality following trans-catheter aortic valve replacement (TAVR) remain high. Renin-angiotensin system inhibitors improve clinical outcomes in the cohort studied in this work. However, post-TAVR prognostic impact of mineralocorticoid receptor antagonist (MRA), another neuro-hormonal blocker, remains uncertain. Here, we hypothesized that MRA was associated with improved clinical outcomes in elderly patients with severe aortic stenosis receiving TAVR. Methods: Consecutive patients who received TAVR at our institute between 2015 and 2022 were considered for inclusion. Propensity score matching analysis was performed to match pre-procedural baseline characteristics between those with and without MRA. The prognostic impact of MRA use on the composite primary endpoint consisting of all-cause death and heart failure during the 2-year observational period following index discharge was evaluated. Results: Among 352 patients who received TAVR, 112 patients (median 86 years, 31 men) were included, consisting of baseline-matched 56 patients with MRA and 56 patients without MRA. Following TAVR, patients with MRA had more impaired renal function compared with no MRA group. Following index discharge, serum potassium tended to increase, and renal function tended to decline in patients with MRA. Patients with MRA had a higher cumulative incidence of the primary endpoints during a two-year observational period (30% versus 8%, p = 0.022). Conclusions: Routine prescription of MRA might not be recommended in elderly patients with severe aortic stenosis receiving TAVR, given its negative prognostic impact. Optimal patient selection for MRA administration in this cohort needs further study.

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a phenotype of pulmonary hypertension due to chronic and multiple organized thrombus. The therapeutic strategy for patients with CTEPH and comorbid protein S deficiency remains unknown due to its rarity. Case: We encountered a 49-year-old male patient with CTEPH and concomitant mild protein S deficiency (type III). We could successfully perform balloon pulmonary angioplasty without any major complications, including thromboembolism and bleeding, followed by standard-dose oral anticoagulation therapy instead of warfarin. Conclusion: A currently established standard therapeutic strategy for CTEPH, including pulmonary angioplasty, may be safe and effective even in patients with concomitant inherent coagulation abnormalities.

Cardiac amyloidosis usually presents with diastolic dysfunction, but sometimes systolic dysfunction develops, particularly at its advanced stage. However, the therapeutic strategy for patients with cardiac amyloidosis and systolic dysfunction remains unknown. We report a 77-year-old man who was diagnosed with wild-type cardiac amyloidosis and systolic dysfunction with a left ventricular ejection fraction of 27%. Following 6-month medical therapy of tafamidis 80 mg and neurohormonal blockers (carvedilol 5.0 mg, enalapril 2.5 mg, and spironolactone 25 mg), the left ventricular ejection fraction improved to 55%. Tafamidis-incorporated neurohormonal blocker therapy might be a promising strategy to facilitate cardiac reverse remodeling in patients with cardiac amyloidosis and systolic dysfunction.

Background: The six-minute walk test is a practical tool for assessing functional capacity in patients with a variety of etiologies including pulmonary disease and heart failure. Six-minute walk distance (6MWD) is associated with mortality and morbidity in patients with a variety of comorbidities. We aimed to assess the prognostic impact of baseline 6MWD in patients with severe aortic stenosis undergoing trans-catheter aortic valve replacement (TAVR). Methods: Patients with severe aortic stenosis who underwent a six-minute walk test after index admission and underwent TAVR between 2015 and 2022 were included in this retrospective study. Patients were followed up for two years or until November 2022 following TAVR. The impact of baseline 6MWD on the primary composite outcome, defined as all-cause death and all-cause readmission during the 2-year observation period following index discharge, was assessed. Results: A total of 299 patients (median age 86 years old, 85 men) were included. They received a 6-min walk test prior to TAVR, underwent successful TAVR procedures, and were discharged alive. The median baseline 6MWD was 204 (143, 282) meters. Shorter baseline 6MWD was associated with higher cumulative incidence of the primary outcome with an adjusted hazard ratio of 0.76 (95% confidence interval 0.58–1.01, p = 0.055) with a cutoff 6MWD of 178 m during the 2-year observation period after index discharge. Conclusions: Overall, functional capacity was impaired in the elderly patients with severe aortic stenosis prior to TAVR. Patients with severe aortic stenosis having shorter baseline 6MWD tended to have higher rates of morbidity and mortality after successful TAVR. The clinical implication of aggressive cardiac rehabilitation to improve patients’ functional capacity and 6MWD-guided optimal patient selection remain the future concerns.

Background: Polypharmacy in elderly patients with various comorbidities is associated with mortality and morbidity. However, the prognostic impact of polypharmacy in patients with severe aortic stenosis receiving trans-catheter aortic valve replacement remains unknown. Methods: Patients with severe aortic stenosis who received trans-catheter aortic valve replacement between 2015 and 2022 and were followed up at our institute following index discharge were included in this retrospective study. The impact of polypharmacy, which was defined as medication numbers ≥10 at index discharge, upon 2-year all-cause death was investigated. Results: A total of 345 patients (median age 85 [83, 89] years old, 99 (29%) men) were included. Median medication number was 9 (7, 10) at the index discharge and 88 (26%) were classified as receiving polypharmacy. Frailty index, including mini-mental state examination and CSHA score, were not significantly different between those with and without polypharmacy (p > 0.05 for both). Polypharmacy was associated with higher 2-year cumulative mortality with an adjusted hazard ratio of 21.4 (95% confidence interval, 6.06–74.8, p < 0.001). As a sub-analysis, the number of cardiovascular medications was not associated with 2-year mortality (hazard ratio 1.12, 95% confidence interval 0.86–1.48, p = 0.46), whereas a higher number of non-cardiovascular medications was associated with an incremental increase in 2-year mortality with a hazard ratio of 1.39 (95% confidence interval, 1.15–1.63, p < 0.001). Conclusions: In elderly patients with severe aortic stenosis, polypharmacy was associated with worse short-term survival following trans-catheter aortic valve replacement. Prognostic implication of aggressive intervention to decrease the amount of medication among those receiving TAVR requires further prospective studies.

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality and morbidity in patients with heart failure (HF), but are discontinued in some patients. Such patients may not enjoy favorable benefits of SGLT2i therapy. We evaluated the risk factors for SGLT2i discontinuation in a real-world population with HF. Methods: We retrospectively included consecutive patients who were hospitalized for HF and administered SGLT2i during the index hospitalization between February 2016 and September 2021. We assessed the baseline clinical factors associated with post-discharge discontinuation of SGLT2i. Results: This study included a total of 159 patients (median age = 73 years, 57 women). Among baseline characteristics, a lower serum albumin level (odds ratio = 0.23, 95% confidence interval = 0.07–0.76, p = 0.016) and a higher dose of furosemide (odds ratio = 1.02, 95% confidence interval = 1.00–1.05, p = 0.046) were independently associated with the future discontinuation of SGLT2i following index discharge. Patients who terminated SGLT2i (n = 19) had a higher incidence of HF recurrence or cardiovascular death during the 1-year therapeutic period (32% versus 11%, p = 0.020). Conclusions: Among patients who initiated SGLT2i during hospitalization for HF, lower serum albumin levels and higher doses of loop diuretic at index discharge were associated with the discontinuation of SGLT2i following index discharge. We should pay special attention to patients with such characteristics during the initiation of SGLT2i and during SGLT2i therapy.

Combined cases of hypertrophic obstructive cardiomyopathy (HOCM) and pulmonary arterial hypertension (PAH) are rare and have a management dilemma. Although preload is crucial in the management of HOCM, anti-PAH agents dramatically change the preload, leading to improving or worsening heart failure in patients with HOCM. We had a 74-year-old woman with Sjogren-syndrome-associated PAH. Her heart failure worsened following the initiation of anti-PAH agents due to an incremental preload on the left ventricle, whereas HOCM clinically developed following the termination of anti-PAH agents and progressing anorexia due to the progression of the left ventricular outflow obstruction. Careful monitoring of the left ventricular outflow obstruction during initiation/termination of anti-PAH agents and medical intervention to the HOCM are highly recommended.

Nerve growth factor (NGF) is the main neurotrophic factor that can control sympathetic nerve innervation and sympathetic neural activity in cardiovascular organs. Although NGF overproduction and its influences on the sympathetic nervous system have been shown in hypertensive animals, NGF status and its association with sympathetic nerve activity have not yet been explored in human hypertension. In the present study, therefore, plasma and urinary levels of NGF and those of catecholamines (i.e., indices for NGF status and sympathoadrenal activity, respectively) were compared between 83 untreated primary hypertensives without apparent cardiovascular damages and 81 healthy normotensive subjects. Plasma and urinary levels of NGF were significantly greater in the hypertensive group (311 ± 158 pg/mL and 72.7 ± 54.0 ng/g of Cr) than in the normotensive group (168 ± 188 pg/mL and 54.5 ± 38.8 ng/g of Cr) (p

Background and Objectives: Small dense LDL cholesterol is a strong risk factor for atherosclerosis. However, few studies have investigated the impacts of this specific lipid profile on the incident risk of adverse cardiovascular events in patients with acute coronary syndrome. Materials and Methods: Patients with acute coronary syndrome, who underwent revascularization, were included and followed for 2 years. The levels of small dense LDL cholesterol were measured at index discharge (day 0) in the setting of newly administered therapies for secondary prevention, including aspirin and statins, during the index hospitalization. The prognostic impact of small dense LDL-cholesterol levels on the risk of a primary composite endpoint, including cardiac death, non-fatal myocardial infarction, unstable angina pectoris, stroke, and heart failure, was investigated. Results: In total, 46 patients (median 75 (59, 83) years old, 63% men) were included. Median small dense LDL cholesterol was 19.4 (13.5, 23.8) mg/dL at index discharge. All patients initiated statin treatment before the index discharge, with a median LDL-cholesterol level of 77 (64, 109) mg/dL. Small dense LDL-cholesterol level was independently associated with an incremental risk for the primary endpoint (p < 0.05 by adjusting for several potential risk factors, including LDL cholesterol) with a cutoff of 32.6 mg/dL. Conclusions: Small dense LDL-cholesterol level was a significant risk factor for cardiovascular events following presentations of acute coronary syndrome.

Background: Pulmonary congestion is quantified by a remote dielectric sensing (ReDSTM) system, while systemic congestion is estimated by calculated plasma volume. The type of clinical patient profile as defined by the ReDS system and calculated plasma volume remains uncertain. Methods: Hospitalized patients with or without heart failure were included in this prospective study. On admission, ReDS values were measured and plasma volume status (PVS) was estimated using their body weight at the same time. Cutoffs of ReDS value and PVS were defined at 34% and −2.7%, respectively. The association between the two parameters was assessed. Results: A total of 482 patients (median 76 years, 288 men) were included. The median ReDS value was 28% (25%, 32%) and median PVS was −16.4% (−26.3%, −5.9%). Of the patients, 64 had high ReDS value (and low PVS) and 80 had high PVS (and low ReDS value). The high ReDS group had a higher prevalence of clinical heart failure with a more elevated echocardiographic E/e’ ratio, whereas the high PVS group had a higher prevalence of chronic kidney disease (p < 0.05 for all). Four out of a total of six patients with high ReDS value and high PVS had both heart failure and chronic kidney disease profiles. Conclusion: The combination of ReDS value and PVS was able to clinically stratify the types of body fluid distribution and patient profiles. Utilizing these tools may assist the clinician in constructing a therapeutic strategy for the at-risk hospitalized patient.

Background: In patients with essential hypertension, a non-dipping blood pressure pattern is a strong risk factor for cardiovascular diseases. However, background factors associating with such a blood pressure pattern remain unknown. Methods: Untreated essential hypertensive patients without chronic kidney diseases who were admitted to our outpatient clinic were included. Blood sampling and 24 h ambulatory blood pressure monitoring were mandatorily performed. Non-dipper status was defined as a maximum decrease in nocturnal systolic blood pressure within 10%. Clinical factors associating with non-dipper status were investigated. Results: A total of 154 patients (56 ± 12 years old, 86 men) were included. Among baseline characteristics, a higher serum uric acid level was independently associated with non-dipper status (odds ratio 1.03, 95% confidence interval 1.00–1.05, p < 0.05). Among those with non-dipper status, a higher high-sensitivity C-reactive protein level tended to be associated with incremental nighttime systolic blood pressure levels (p = 0.065). Conclusions: Hyperuricemia and micro-inflammation might be associated with attenuated nocturnal blood pressure dipping and incremental nighttime systolic blood pressure levels.

Background: Chest X-ray is a practical tool to semi-qualify pulmonary congestion. Remote dielectric sensing (ReDS) is a recently introduced, non-invasive, electromagnetic energy-based technology to quantify pulmonary congestion without expert technique. We compared these two modalities to clarify appropriate clinical situations for each modality. Methods: ReDS and chest X-ray measurements were prospectively performed on admission in consecutive hospitalized patients with cardiovascular diseases. In the chest X-ray, the congestive score index (CSI) was calculated blindly by two independent experts and averaged. CSIs were correlated with ReDS values. Results: A total of 458 patients (76 (69, 82) years old, 267 men, and 130 heart failure) were included. Median ReDS value was 28% (25%, 33%). There was a mild correlation between ReDS values and CSIs (r = 0.329, p < 0.001). The correlation between ReDS values and CSIs became stronger in the heart failure cohort (r = 0.538, p < 0.001). In patients with mild congestion (ReDS < 35%), ReDS values, instead of CSI, stratified the degree of congestion. In patients with severe congestion (ReDS > 35%), both modalities stratified the degree of congestion. Conclusions: Both chest X-ray and ReDS are useful for assessing severe pulmonary congestion, whereas ReDS would be preferred to chest X-ray in stratifying the severity of mild pulmonary congestion.

Background: pemafibrate is a newly-introduced selective peroxisome proliferator-activated receptor-α modulator, which decreases serum triglyceride levels with few drug-related adverse events and may reduce the risk of adverse cardiovascular events in carefully selected patients with hypertriglyceridemia. We aimed to understand which specific cohorts may benefit or not from pemafibrate therapy for adverse cardiovascular event risk reduction. Methods: patients with hypertriglyceridemia at baseline received pemafibrate therapy for two years or until October 2022. The factors that were associated with an increased risk of adverse cardiovascular events, defined as heart failure hospitalization, stroke, and acute coronary syndromes, were investigated. Results: a total of 121 patients (median 62 years, 88 men) remained on pemafibrate therapy for a median of 566 days without any drug-related adverse events. During a 3-month therapeutic period, triglyceride levels improved significantly from 302 (205, 581) mg/dL to 178 (117, 253) mg/dL (p < 0.001). During the overall therapeutic period, there were nine cardiovascular events. Comorbid chronic heart failure, comorbid coronary disease, and a lower pemafibrate dosing were independently associated with the primary endpoint (p < 0.05 for all). Those with multiple risk factors (N = 30) had a significantly higher cumulative incidence of the primary endpoint as compared with others (27% versus 3%, p < 0.001). Conclusion: pemafibrate significantly improves hypertriglyceridemia. A higher dose of pemafibrate should be considered to reduce the risk of adverse cardiovascular events, particularly in patients with chronic heart failure or coronary disease.

Background: Restriction of oral potassium intake is a necessary dietary intervention for managing chronic hyperkalemia. These dietary changes may have negative impacts on nutrition status, particularly in geriatric cohorts with multiple comorbidities. Sodium zirconium cyclosilicate (SZC) is a newly introduced potassium binder intended for patients with hyperkalemia. We aimed to investigate whether the improvements in hyperkalemia with SZC therapy and the liberation of potassium intake restriction may improve nutrition status in a primarily geriatric patient cohort with chronic hyperkalemia. Methods: Patients who were maintained on SZC therapy for at least 3 months were retrospectively studied. Following the initiation of SZC and improvement in hyperkalemia, instructions on the restriction of potassium intake were loosened according to the institutional protocol. The change in nutrition status during the 3 month therapeutic period using SZC was investigated by referencing the prognostic nutritional index score (PNI), geriatric nutritional risk index score (GNRI), and controlling nutritional status (CONUT) scores. Results: A total of 24 patients (median age 78 years, 58% men, median estimated glomerular filtration rate 29.8 mL/min//1.73 m2) were included. Serum potassium level decreased significantly from 5.4 (5.1, 5.9) to 4.4 (4.2, 4.9) mEq/L without any drug-related adverse events, including hypokalemia. Nutrition-related scores, including the PNI score, the GNRI score, and the CONUT score, improved significantly following 3 months of SZC therapy (p < 0.05 for all). Psoas muscle volume and average days for one movement also improved significantly during the therapeutic period (p < 0.05 for both). Conclusions: Mid-term SZC therapy and liberation of potassium intake restriction might improve nutrition status in geriatric patients with chronic hyperkalemia.

Background: Sodium zircon`ium cyclosilicate (SZC), a recently introduced potassium binder, is indicated to treat hyperkalemia. SZC is often terminated soon after the normalization of hyperkalemia in real-world clinical practice. We aimed to investigate the risk factors for the rapid recurrence of hyperkalemia following cessation of SZC. Methods: Patients in whom SZC was discontinued following an improvement in hyperkalemia were followed up for three months. The baseline characteristics that were associated with the rapid recurrence of hyperkalemia (>5.0 mEq/L of serum potassium levels within 3 months) were investigated. Results: A total of 44 patients terminated SZC following the normalization of hyperkalemia. The median age was 81 (69, 87) years old, and 59% were men. When evaluating baseline characteristics, a higher dose of renin-angiotensin system inhibitors was significantly associated with the recurrence of hyperkalemia (adjusted hazard ratio of 1.26, 95% confidence interval 1.02–1.69, p = 0.045) at a designated cutoff of 2.5 mg/day of equivalent enalapril dose. Conclusions: SZC should be considered for ongoing continuation after normalization of hyperkalemia, particularly in patients receiving a relatively higher dose of renin-angiotensin system inhibitors.