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Abstract Heart failure (HF) is a frequent complication and the main cause of death in patients on dialysis. HF with preserved ejection fraction (HFpEF) is a complicated syndrome that manifests as diastolic dysfunction and increased left ventricular filling pressure. Few studies have investigated HFpEF in dialysis patients, so the diagnosis and treatment of HFpEF remains challenging. The recently published the Japanese Circulation Society (JCS)/the Japanese Heart Failure Society (JHFS) 2021 guidelines have reported a new diagnostic procedure for HF. In dialysis patients, HF is typically observed as left ventricular diastolic dysfunction in association with HFpEF. Recent reports have shown that risk factors for HF in dialysis patients include not only traditional risk factors, such as age, smoking, obesity, hypertension, dyslipidemia, and diabetes, but also nontraditional risk factors such as fluid overload, renal anemia, disorders of calcium and phosphate metabolism, uremic toxins, and malnutrition. In the management of dialysis patients, volume control is important for controlling intradialytic hypotension, which is associated with higher mortality. Also, adequate pharmacological treatment of HFpEF is difficult in these patients, so a robust protocol developed for non-dialysis patients with HFpEF may be useful for treating patients on dialysis. This review explores the characteristics of hemodialysis patients with HFpEF and diagnostic and treatment procedures for these patients.

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.

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: 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 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.

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

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.

Abstract Background Sodium-glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of the composite renal endpoint and weakens the progressive decline in renal function in patients with chronic heart failure (HF). However, a detailed mechanism of SGLT2i on renal function and outcome remains uninvestigated. Methods We prospectively included 40 type 2 diabetic mellitus (T2DM) patients (median 68 years old, 29 male) who were hospitalized for decompensated HF and received SGLT2i during the index hospitalization. Of them, 24 patients had increases in estimated glomerular filtration rate (eGFR) at 12-month follow-up and 16 had decreases in eGFR. We investigated the baseline factors associating with the improvement in renal function. Results Lower plasma B-type natriuretic peptide (BNP) level and the use of renin-angiotensin system inhibitor (RASI) were independently associated with increases in eGFR during the follow-up period (p

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 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.

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.

Abstract While patients with acute heart failure often have tachycardia with atrial fibrillation, there have been no established medical tools that control tachycardia safely and definitely. Digoxin has been recommended as a first choice in the former guidelines, but it takes time to affect and has a risk of adverse events particularly for those with chronic kidney disease. Landiolol is a recently innovated ultra‐short‐acting beta‐blocker with 251‐fold β1/β2 selectivity, which was originally indicated only to control peri‐operative supra‐ventricular tachyarrhythmia by 2013 in Japan. We aimed to review how to use landiolol in patients with cardiac dysfunction and tachycardia due to atrial fibrillation. We reviewed recently conducted randomized control trials using landiolol, recently updated guidelines, as well as current practical use of landiolol. Japan landiolol vs. Digoxin (J‐Land) study demonstrated that landiolol was more effective to control tachycardia than digoxin in atrial fibrillation patients with left ventricular dysfunction in 2013. Given the result, the revised Japanese heart failure guideline recommends landiolol for rate control during atrial fibrillation in acute heart failure patients as Class IIa with evidence level B. Currently in Japan, landiolol is used for rate control, even in patients with advanced heart failure receiving continuous infusion of inotropes. The clinical use of landiolol in patients with cardiac dysfunction and tachycardia due to atrial fibrillation is increasing. Further studies are warranted to investigate the implication of faster and safer rate control using landiolol.

Abstract Aims Heart rate reduction therapy using ivabradine, a selective inhibitor of the funny current of the sinoatrial node, is widely used in the systolic heart failure cohort. However, the optimal target of heart rate remains controversial. The association between heart rate and ‘overlap’ between E‐wave and A‐wave in the pulse wave transmitral flow Doppler echocardiography might be a key to find the ideal heart rate in each individual. Methods and results We performed transthoracic echocardiography in patients with systolic heart failure, and the association between heart rate, deceleration time, and overlap length between E‐wave and A‐wave was assessed. In total, 368 patients with systolic heart failure (median 76 years old, 190 men, median ejection fraction 40%) were included. The measured overlap length was 35 (−72, 115) ms. Given the results of multiple linear regression analyses, we constructed a formula: estimated overlap length (ms) = −589 + 6.2 × heart rate (bpm) + 0.81 × deceleration time (ms), which had a good agreement with actually measured one (r = 0.62). The ideal heart rate, at which the overlap length is ‘zero’ and probably cardiac output is maximized, is calculated as follows: ideal heart rate (bpm) = 93 – 0.13 × deceleration time (ms). Conclusions We proposed a novel formula using deceleration time to estimate ideal heart rate that achieves a zero overlap between E‐wave and A‐wave in patients with systolic heart failure. Prognostic impact of the formula‐guided heart rate optimization should be studied.

Abstract Background When we encounter patients who present with both a neck mass and nephrotic syndrome, both malignancy and Kimura’s disease need to be evaluated as the therapeutic strategies differ vastly between them. Case presentation We present the case of a 27-year-old male patient with neck mass and nephrotic syndrome. The presence of both eosinophilia and elevated immunoglobulin E levels were concerning for Kimura’s disease, which is an allergic syndrome defined by eosinophilic granulomas of neck soft tissue along with peripheral eosinophilia. The eventual final diagnosis, however, was sclerosing mucoepidermoid carcinoma of parotid gland with both eosinophilia and membranous nephropathy. Following the surgical resection of the mass, the nephrotic syndrome completely resolved. Conclusion Detailed histopathological assessments of both the parotid gland and renal tissue were key aspects of the diagnosis and management to exclude Kimura’s disease.

Abstract Background Epicardial adipose tissue (EAT) contributes to atrial fibrillation (AF). However, its impact on the efficacy of left atrial posterior wall isolation (LAPWI) is unclear. Methods Forty‐four nonparoxysmal AF patients underwent LAPWI after pulmonary vein isolation. EAT overlap on LAPWI was assessed by fusing computed tomography images with electro‐anatomical mapping. Results During the 21 ± 7 months of follow‐up, AF recurred in 10 patients (23%). The total and left atrial EAT volumes were 113 ± 36 and 33 ± 12 cm3, respectively. No differences were found between the AF‐free and AF‐recurrent groups regarding EAT volume. The EAT overlaps on LAPWI lines and LAPWI area were 1.2 ± 1.0 and 0.5 ± 0.9 cm2 respectively. Although no difference was found between groups regarding the EAT overlap on LAPWI area, the AF‐free group had a significantly larger EAT overlap on LAPWI lines (1.4 ± 1.0 vs 0.6 ± 0.6 cm2, P = .014). Multivariate analysis identified EAT overlap on LAPWI lines as an independent predictor of AF recurrence (hazard ratio: 0.399, 95% confidence interval: 0.178‐0.891, P = .025). Kaplan‐Meier analysis revealed that, during follow‐up, 92% of the large EAT overlap group (≥1.0 cm2) and 58% of the small EAT overlap group (

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: 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.

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.

Abstract Background The impact of the left atrial low‐voltage area (LVA) on the cardiac function improvement following ablation for atrial fibrillation (AF) is unclear. Methods In 49 patients with paroxysmal AF who underwent ablation, the left ventricular stroke volume index (SVI) was repeatedly measured using an impedance cardiography until 6 months after ablation. We defined the cardiac function improvement as a 20% increase in the SVI. The LVA (the area with the voltage amplitude of

Abstract Background The impact of left atrial posterior wall isolation (LAPWI) on the complex fractionated atrial electrogram (CFAE) is unknown. Methods CFAE mapping was performed before and after LAPWI in 46 patients with persistent atrial fibrillation (AF). Results LAPWI decreased both the variable (fractionated index ≤ 120 ms; from 60 ± 4 cm2 to 50 ± 4 cm2, P

Background and Objectives: Percutaneous mitral valve repair using a MitraClip system is an established therapeutic strategy to treat severe mitral regurgitation, which is recommended by guidelines in Europe and in the United States, whereas residual mitral regurgitation is associated with mortality and morbidity. Accurate assessment of residual mitral regurgitation is crucial for risk stratification and further adequate intervention, whereas its quantification has technical limitations due to “double” regurgitation that is often encountered following valve clipping. Remote dielectric sensing (ReDSTM) is a non-invasive electromagnetic-based technology to quantify lung fluid levels and might be a promising tool to assess the impact of residual mitral regurgitation following MitraClip. Materials and Methods: Following MitraClip, ReDS values measurements and right heart catheterization were performed and correlated. Results: We had 13 patients (median 74 years, 7 men) who underwent successful MitraClip. According to the visual estimation, eight patients had none or mild regurgitation, and five patients had moderate regurgitation. ReDS values were distributed widely between 16% and 33%, irrespective of the severity of regurgitation. ReDS values had a moderate correlation with invasively measured pulmonary artery wedge pressure (r = 0.73, p = 0.004). Conclusions: ReDS value might be a promising tool to assess residual pulmonary congestion following MitraClip, irrespective of the visually estimated severity of residual mitral regurgitation.

Exercise-induced mitral regurgitation (MR) can be diagnosed during stress echocardiography testing. Remote dielectric sensing (ReDSTM) is a noninvasive electromagnetic-based modality to measure lung fluid levels. The change in lung fluid levels in patients with MR during stress echocardiography remains unknown. Patients with symptomatic MR at baseline and suspected worsening exercise-induced MR underwent stress echocardiography. ReDS values were measured before and after the tests. A total of four patients (ages ranging between 74 and 84 years old, three women) underwent stress echocardiography testing using a bicycle ergometer. In patient A, MR effective regurgitant orifice area (EROA) remained unchanged and ReDS values decreased. EROA increased significantly with a small incremental change in ReDS values in patient B and patient C, who underwent valve repair with MitraClip later. Patient D had a mild increase in MR EROA but a considerable increase in ReDS values (from 22% to 32%), and eventually received valve repair with MitraClip. The ReDS system may be a complementary tool to conventional stress echocardiography in the evaluation of clinically significant MR and considering mitral valve intervention.

Potassium binders are essential tools to treat hyperkalemia, particularly in patients with heart failure and chronic kidney disease. One of the drug-related complications is constipation, which further worsens heart failure by increasing afterload and decreases patients’ quality of life. We encountered an 82-year-old man with heart failure, chronic kidney disease, and hyperkalemia. A conventional potassium binder, calcium polystyrene sulfonate, ameliorated his hyperkalemia, whereas he became aware of refractory constipation. A conversion to a newly-introduced specific potassium binder, sodium zirconium cyclosilicate, improved persistent constipation, maintaining serum potassium levels within a normal range. Sodium zirconium cyclosilicate might be a preferable potassium binder to treat hyperkalemia, particularly in patients with heart failure and chronic kidney disease and those suffering from constipation.

Background and Objectives: Cardiopulmonary exercise testing can be used to quantify exercise capacity in patients with heart failure with reduced ejection fraction (HfrEF). Lung fluid levels as measured non-invasively by remote dielectric sensing (ReDSTM), often correlate with intracardiac filling pressures. The change in lung fluid levels in patients with HfrEF during cardiopulmonary exercise testing is unknown. Materials and Methods: Patients with chronic HfrEF who underwent cardiopulmonary exercise testing between October 2021 and March 2022 were prospectively included in this proof-of-concept study, with ReDS values measured before and after testing. Results: Thirteen patients (median age 41 (37, 52) years, 69% men, plasma B-type natriuretic peptide 141 (57, 368) pg/mL) were included. Median peak oxygen consumption was 11.4 (10.7, 14.0) mL/kg/min. During the test, ReDS values increased from 25% to 32% only in one patient on inotropic support, whereas ReDS values remained unchanged in the other 12 patients. The former patient remained hospitalized, whereas the other patients were dischargeable without any new incidence of clinical events during the observational period (median duration 69 (33, 112] days). Conclusions: The ReDS system may be a feasible complementary tool to noninvasively assess the changes in lung fluid levels during cardiopulmonary exercise testing. The clinical implications of ReDS values during exercise needs further investigation.

Background: The therapeutic strategy for mitral regurgitation (MR) in patients with advanced heart failure and wide QRS complex who are indicated for both intervention to MR and cardiac resynchronization therapy (CRT), remains unclear. Objective: We aimed to determine electrocardiogram parameters that associate with MR reduction following CRT implantation. Methods: Among the patients with advanced heart failure and functional MR who intended to receive CRT implantation, baseline QRS morphology, electrical axis, PR interval, QRS duration, and averaged S-wave in right precordial leads (V1 to V3) in surface electrocardiogram were measured. The impact of these parameters on MR reduction following CRT implantation, which was defined as a reduction in MR ≥1 grade six months later, was investigated. Results: In 35 patients (median 71 years old, 18 men), 17 (49%) achieved an MR reduction following CRT implantation. Among baseline characteristics, only the higher S-wave amplitude in right precordial leads was an independent predictor of MR reduction (odds ratio 14.00, 95% confidence interval 1.65–119.00, p = 0.016) with a cutoff of 1.3 mV calculated through the area under the curve. The cutoff significantly stratified the cumulative incidences of heart failure re-admission and percutaneous mitral valve repair following CRT implantation (p = 0.032 and p = 0.011, respectively). Conclusions: In patients with advanced heart failure and functional MR, the baseline higher amplitude of S-wave in the right precordial leads might be a good indicator of MR improvement following CRT.

The use of veno-arterial extracorporeal membrane oxygenation (ECMO) in patients with sepsis-induced cardiogenic shock has been reported, but the clinical implication of the Impella percutaneous axial-flow left ventricular assist device for such patients remains unknown. We had a 37-year-old man with septic shock and severely reduced cardiac function. Veno-arterial ECMO and concomitant Impella CP support ameliorated his end-organ dysfunction and achieved cardiac recovery, whereas severe mitral valve regurgitation due to chordal rupture developed later. Mitral valve replacement concomitant with ECMO removal as well as an Impella upgrade successfully treated the patient. ECMO and Impella support might be an effective therapeutic strategy for the bridge to recovery in patients with sepsis-induced cardiogenic shock; however, paying attention to mitral chordal rupture is highly encouraged.

Remote dielectric sensing (ReDSTM) is a novel technology that noninvasively quantifies lung fluid levels. Trends in ReDS values following hemodialysis remain uninvestigated. In a 64-year-old man with clinically stable hemodynamics, 2.7 L of fluid was drained during hemodialysis whereas the ReDS value remained almost unchanged (from 32 to 30%). In a 60-year-old woman with unstable hemodynamics, only 1.8 L of fluid was drained during hemodialysis, whereas ReDS value decreased considerably from 37 to 27%. Given our initial experience measuring ReDS values during hemodialysis, the ratio of fluid removal by hemodialysis between systemic plasma and lung fluid might vary in each patient. ReDS value might be a promising marker to determine the degree of fluid removal in addition to the conventional multidisciplinary index, particularly for those with unstable hemodynamics. The implications of ReDS-guided hemodialysis remain a future concern.

Background and Objectives: Acquired von Willebrand syndrome (AVWS) develops not only in patients with durable ventricular assist devices but also in patients receiving temporary mechanical circulatory support (MCS). However, its prognostic implication remains unknown. Materials and Methods: Patients who received temporary MCS in our institute between August 2018 and September 2021 were included in this prospective study and the von Willebrand factor multimer analyses were performed following the initiation of temporary MCS supports. The von Willebrand factor large-multimer index was calculated as a normalized ratio of large-multimer proportion among total von Willebrand factor. Association between the large-multimer index and the 30-day survival was investigated. Results: A total of 31 patients (69 years old, 52% men) were included. Median large-multimer index was 63.0% (56.9%, 75.6%). The index was lowest in patients with extracorporeal membrane oxygenation than those receiving support from other devices. A lower index (p = 0.001) with an odds ratio 0.044 (95% confidence interval 0.002–0.805, p = 0.035) adjusted for other potential confounders. Conclusions: An advanced AVWS was associated with lower short-term survival in patients with temporary MCS. The clinical implication of AVWS-guided temporary MCS management remains the next concern.

Cancer therapeutics-related cardiac dysfunction is currently of great concern as one of the pivotal therapeutic targets of onco-cardiology. Only a few studies have reported the occurrence of heart failure following the administration of osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor for EGFR mutation-positive advanced non-small cell lung cancer. We report on a 74-year-old woman with osimertinib-induced advanced heart failure with reduced ejection fraction, which was treated by the temporal termination of osimertinib and neurohormonal blocker therapy, as well as heart rate modulation therapy using ivabradine. Despite osimertinib-induced heart failure being relatively rare, aggressive neurohormonal blocker therapy using ivabradine if applicable, as well as the temporal termination of osimertinib, might be a promising therapeutic strategy.

Therapeutic strategy utilizing mechanical circulatory supports in patients with pheochromocytoma-related cardiogenic shock remains unestablished. We had a 51-year-old man with acute decompensated heart failure due to pheochromocytoma crisis. He received a percutaneous left ventricular assist device-supported alpha-blocker and intensive fluid infusion therapy, which ameliorated impaired end-organ dysfunction, maintaining hemodynamics and achieving cardiac recovery, followed by the successfully scheduled adrenalectomy. Early suspicion of pheochromocytoma and Impella-supported disease-specific medical management might be a promising bridge to surgery strategy.

Mortality and morbidity remain high following transcatheter aortic valve replacement (TAVR) in dialysis patients or those with low left ventricular ejection fraction. Therapeutic strategy for those with these comorbidities remains unestablished. We had a dialysis patient with peripheral artery disease and low left ventricular ejection fraction, who received successfully scheduled trans-apical TAVR following sufficient reverse remodeling by 3-month optimal medical therapy. Our strategy should be validated in a larger robust cohort.

Post-transplant lymphoproliferative diseases (PTLD) are potentially fatal complications after cardiac transplantation. Most cases are Epstein–Barr virus (EBV)-related B-cell tumors, and reduction of immunosuppression treatment as well as the use of rituximab in combination with other chemotherapy are effective. However, patients with T/NK-cell PTLD post-cardiac transplantation are rarely reported. We had a patient with a fever that lasted for three weeks, with lung infiltrations and hepatosplenomegaly, who had EBV-associated hemophagocytosis 7 years after heart transplantation and was eventually diagnosed with T/NK-cell PTLD by autopsy. Although rare diseases, regular monitoring of EBV-DNA levels might be crucial for early diagnosis and treatment of PTLD.

Heart rate reduction using ivabradine, a selective If channel blocker that purely decreases heart rate without affecting hemodynamics, improves clinical outcomes in patients with systolic heart failure. However, the ideal heart rate that should be a target remains unknown. Our team recently proposed a methodology using Doppler echocardiography to estimate ideal heart rate, at which E-wave and A-wave stand adjacent without overlap. However, the implication of Doppler echocardiography-guided heart rate modulation therapy using ivabradine remains uncertain. We had a 72-year-old man with systolic heart failure and sinus tachycardia who initiated ivabradine therapy. Ivabradine dose was adjusted between 5.0 mg/day and 10.0 mg/day and continued for 12 weeks to minimize the overlap between the two echocardiography waves, accompanying improvement in cardiac output, left ventricular ejection fraction, plasma B-type natriuretic peptide, and six-minute walk distance. Doppler echocardiography-guided heart rate regulation therapy using ivabradine may be a promising strategy to improve cardiac function and clinical outcomes in patients with systolic heart failure, although further studies are required to validate this hypothesis.

Background: Optimal heart rate (HR) that associates with higher cardiac output and greater clinical outcomes in patients with cardiac amyloidosis remains unknown. Methods: Consecutive patients with sinus rhythm who were diagnosed with cardiac amyloidosis at our institute between February 2015 and February 2021 were retrospectively included. Ideal HR, at which E-wave and A-wave stand adjacent without any overlaps in the trans-mitral flow echocardiography, was calculated by the formula: 86.8−0.08 × deceleration time (msec). The association between optimal HR and cardiac death or heart failure readmission was investigated. Results: Ten patients (median 74 years old, 8 men) were included. On median, actual HR was 64 bpm and ideal HR was 69 bpm. An incidence rate of the primary endpoint in the sub-optimal HR group tended to be higher than optimal HR group: one of the four patients in optimal HR group had events (25%); two of the two patients in higher HR group had events (100%); two of the four patients in lower HR group had events (50%). Conclusions: The optimal HR was associated with greater clinical outcomes in patients with cardiac amyloidosis. The clinical impact of aggressive HR optimization in this cohort remains the next concern.

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor is a recently introduced oral agent to treat renal anemia, but its clinical implications on renal functioning in patients with heart failure remains unknown. We studied an 81-year-old man with heart failure with mildly reduced ejection fraction, chronic kidney disease, and renal anemia. The seven-month HIF-PH inhibitor daprodustat treatment improved the hemoglobin level from 7.4 g/dL to 11.8 g/dL and estimated glomerular filtration ratio from 24 mL/min/1.73 m2 to 35 mL/min/1.73 m2 without any complications, including thromboembolic events. HIF-PH inhibitor might be a promising therapeutic tool to improve renal anemia and renal function in patients with heart failure, although large-scale studies are warranted to validate our findings.

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor is a recently introduced oral medication to treat renal anemia, but its clinical implication in patients with heart failure, particularly heart failure with preserved ejection fraction (HFpEF), remains unknown. We had a 91-year-old woman with HFpEF who was admitted to our institute to treat her worsening heart failure. She initiated HIF-PH inhibitor daprodustat to treat her renal anemia (hemoglobin 8.8 g/dL and estimated glomerular filtration ratio 15.6 mL/min/1.73 m2). Following a 6-month treatment with daprodustat, hemoglobin increased up to 10.4 g/dL, left ventricular mass index decreased from 107 g/m2 to 88 g/m2, and plasma B-type natriuretic peptide decreased from 276 pg/mL to 122 pg/mL, despite doses of other medications remaining unchanged. HIF-PH inhibitors might be a promising tool to ameliorate renal anemia and facilitate cardiac reverse remodeling in patients with HFpEF.

Background and objectives: Endothelial dysfunction is associated with exercise intolerance and adverse cardiovascular events. Transcatheter aortic valve implantation (TAVI) is applied to treat elderly patients with severe aortic stenosis, but less is known about the impact of TAVI on endothelial dysfunction, which can be assessed by measuring flow-mediated vasodilation (FMD). In this parameter, a low value indicates impaired endothelial function. Materials and Methods: Vascular endothelial function was evaluated by FMD of the brachial artery just before and one week after TAVI. Factors associated with the normalization of FMD and their prognostic impact were investigated. Results: Fifty-one patients who underwent TAVI procedure (median 86 years old, 12 men) were included. FMD improved significantly from baseline to one week following TAVI (from 5.3% [3.7%, 6.7%] to 6.3% [4.7%, 8.1%], p < 0.001). Among 33 patients with baseline low FMD (≤6.0%), FMD normalized up to >6.0% following TAVI in 15 patients. Baseline higher cardiac index was independently associated with normalization of FMD following TAVI (odds ratio 11.8, 95% confidence interval 1.12–124; p < 0.04). Conclusions: Endothelial dysfunction improved following TAVI in many patients with severe aortic stenosis. The implication of this finding is the next concern.

Bevacizumab is a recombinant humanized monoclonal antibody and a key drug for treatment of various types of cancer. Bevacizumab is associated with the occurrence of heart failure, but its risk factors remain unknown. A 55-year-old woman was diagnosed with cervical cancer, which was completely treated by bevacizumab-incorporated chemotherapy. During the 9-month bevacizumab therapy, she suffered from hypertension requiring multiple antihypertensive agents. She was admitted to our hospital due to acute heart failure with afterload mismatch and severe mitral regurgitation. A transesophageal echocardiography showed Barlow’s disease with a degenerated and widely prolapsed mitral valve. She received a scheduled surgical mitral valve repair. Post-operative cause was uneventful, but metastatic dissemination developed later. The existence of mitral valve regurgitation, even when sub-clinical, might be a risk of worsening heart failure during bevacizumab therapy. Careful follow-up at an onco-cardiology clinic is highly encouraged particularly for such a cohort during bevacizumab therapy.

Background and objectives: Current guidelines criteria do not satisfactorily discriminate responders to cardiac resynchronization therapy (CRT). QRS amplitude is an established index to recognize the severity of myocardial disturbance and might be a key to optimal patient selection for CRT. Materials and Methods: (1) Initial R-wave amplitude, (2) S-wave amplitude, and (3) a summation of maximal R- or R′-wave amplitude and S-wave amplitude were measured at baseline. These parameters were averaged according to right (V1 to V3) or left (V4 to V6) precordial leads. The impact of these parameters on response to CRT, which was defined as a decrease in left ventricular end-systolic volume ≥15% at six-month follow-up, was investigated. Results: Among 47 patients (71 years old, 28 men) who received guideline-indicated CRT implantation, 25 (53%) achieved the definition of CRT responder. Among baseline electrocardiogram parameters, only the higher S-wave amplitude in right precordial leads was an independent predictor of CRT responders (odds ratio: 2.181, 95% confidence interval: 1.078–4.414, p = 0.030) at a cutoff of 1.44 mV. The cutoff was independently associated with cumulative incidence of heart failure readmission and appropriate electrical defibrillation following CRT implantation (p < 0.05, respectively). Conclusions: Prominent S-wave in right precordial leads might be a promising index to predict left ventricular reverse remodeling and greater clinical outcomes following CRT implantation.

Background and objectives: Leadless pacemakers are less invasive but are as effective as conventional pacemakers and are increasingly implanted in elderly patients. However, the implantation procedure is sometimes challenging in patients with abnormal anatomy, particularly those with an enlarged right heart. We aimed to determine the right heart parameters that were associated with longer procedure times for leadless pacemaker implantation. Materials and Methods: Among 19 consecutive patients in whom Micra leadless pacemakers (Micra TPS, Medtronic, Minneapolis, MN) were implanted, the diameter and area of both the right atrium and right ventricle were measured by transthoracic echocardiography before the procedure. The right heart parameters that were associated with a procedure time > 60 min were investigated. Results: In the 19 patients (median 81 years old, 10 male) who underwent implantation of the Micra system, 6 (32%) required a procedure time > 60 min. Among the baseline right heart echocardiographic parameters, right atrial diameter and area were significantly associated with a procedure time > 60 min (odds ratio 11.3, 95% confidence interval 1.09–1.17, p = 0.042; and odds ratio 1.57, 95% confidence interval 1.05–2.34, p = 0.029, respectively) at a cutoff of 4.0 cm and 17.0 cm2, respectively. Conclusions: Patients with an enlarged right atrium may not be good candidates for leadless pacemakers given the longer procedure time, and conventional pacemakers should perhaps be recommended as an alternative.

Background: Smoking is a risk factor for cardiovascular diseases, but it is unclear whether smoking status, including environmental tobacco smoke, increases stroke risk in patients with atrial fibrillation (AF). Abnormalities of the left atrium (LA) and aortic atherosclerosis, as detected by transesophageal echocardiography (TEE), are risk factors for stroke and thromboembolism in AF patients. We investigated the impact of smoking status on thromboembolic risk by TEE in patients with nonvalvular AF. Methods: In 122 patients with AF (mean age, 63 years; chronic AF 50%) who underwent TEE before catheter ablation of AF or for detection of the potential cardioembolic source, urinary concentrations of cotinine and clinical variables including smoking status and the CHA2DS2-VASc score were determined. Results: Severe aortic atherosclerosis and increased aortic wall thickness were more frequently detected by TEE in current smokers than in non-smokers (p

In the management of atrial fibrillation in patients with heart failure, rate control is recommended, whereas the implication of rhythm control remains controversial. We experienced a 65-year-old man who had compensated heart failure due to hypertensive heart disease and atrial fibrillation with well-controlled heart rate (