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Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) classically present with ventricular arrhythmias and less commonly heart failure. ARVC is an inherited cardiomyopathy and generally based on a variant of desmosomal genes. Recently, the association between myocardial inflammation and ARVC has been a matter of great concern. We encountered a patient with ARVC who had a desmoglein-2 mutation with advanced right ventricular failure accompanying a preserved left ventricular function. Concomitant right ventricular myocarditis was detected four years after the diagnosis of ARVC. ARVC and myocarditis might have a deep pathophysiological association, at least in some cases.

Background: Percutaneous left atrial appendage closure using the WATCHMAN system, to prevent thrombosis and minimize anti-coagulant use in patients with non-valvular atrial fibrillation, has recently been introduced. The safety and efficacy of new-generation WATCHMAN FLX, as compared to conventional WATCHMAN 2.5, remain unknown. Methods: Consecutive patients who received percutaneous left atrial appendage closure using the WATCHMAN system in our institute, between June 2020 and December 2021, were retrospectively analyzed. Safety and efficacy during the 45-day observational period were compared between the two devices. Results: A total of 93 patients (73.0 ± 7.3 years old, 63 men) who received WATCHMAN FLX (n = 44) or WATCHMAN 2.5 (n = 49) were included. The device implant success rate was 100% in the FLX device group and 98% in the 2.5 device group. There were no procedure-related complications in the FLX group, and one non-relevant pericardial effusion in the 2.5 device group. During the 45-day observational period, there were no procedure-related adverse events. No patients in the FLX group had a peri-device leak >3 mm, whereas two patients in the 2.5 device group had a peri-device leak >3 mm. Anti-coagulants could be terminated in most of the patients (85% versus 88%; p = 0.68). Conclusions: Percutaneous left atrial appendage closure using new-generation WATCHMAN FLX seemed to be as safe and effective as conventional WATCHMAN 2.5 during the short-term observational period.

Background: Remote dielectric sensing (ReDS™) is an electromagnetic-based technology used to noninvasively measure lung fluid levels. The association between ReDS values and invasively measured hemodynamics, particularly among those with small physics, remains unknown. Methods: Consecutive patients with chronic heart failure who were admitted to our institute and underwent invasive right heart catheterization as well as simultaneous ReDS measurement at clinically stable conditions between September and November 2021 were prospectively included. The colinearity between ReDS values and pulmonary capillary wedge pressure was studied. Results: In total, 30 patients (median 79 (73, 84) years old, 13 men) were included. Median ReDS value was 26% (22%, 28%). ReDS values had a moderate collinearity with pulmonary capillary wedge pressure (r = 0.698, p < 0.001), even among those with a body height < 155 cm. ReDS values with a cutoff of 28% predicted a pulmonary capillary wedge pressure > 15 mmHg with sensitivity 0.70 and specificity 0.75. Conclusions: An electromagnetic-based engineering ReDS might be a potential tool to estimate cardiac pressure in patients with heart failure, including those with small physics.

In the collecting ducts of the kidney, arginine vasopressin (AVP), cyclic adenosine monophosphate (cAMP), and aquaporin 2 (AQP2) play a pivotal role in maintaining fluid volume and serum osmolality in humans. However, their association among those with chronic kidney disease (CKD) remains uncertain.We prospectively included the out-patients with CKD and measured osmolality-related biomarkers including plasma AVP, urine cAMP, urine AQP2, and urine osmolality levels. Association among these parameters at each CKD stage was investigated.A total of 121 patients were included (median age 71 years old [61-78], 89 men, estimated glomerular filtration ratio 28.6 [16.4-45.3] mL/min/1.73 mVasopressin type-2 receptor seems to be particularly impaired in patients with advanced CKD, whereas the signal cascade of the downstream of vasopressin type-2 receptor is relatively preserved. Urine cAMP might be a promising marker to estimate the residual function of the collecting duct.

Remote dielectric sensing (ReDS) is a recently introduced non-invasive electromagnetic-based device used to quantify lung fluid levels. Nevertheless, its inter-rater and intra-rater reliability remain uncertain. In 10 healthy volunteers, ReDS values were measured three times successively by the officially trained expert examiner to validate intra-rater reliability. Similar measures were performed by a total of three examiners to validate inter-rater reliability. Intra-class correlation (ICC) was applied to validate each reliability. Ten healthy volunteers [median 34 (32, 40) years old, 10 men, body mass index 23.0 (21.2, 23.9) ] were included. Median ReDS value was 28% (25%, 31%). For the intra-rater reliability, ICC (1, 1) and ICC (1, 3) were 0.966 and 0.988, respectively (P0.001). For the inter-rater reliability, ICC (2, 1) and ICC (2, 3) were 0.683 and 0.866, respectively (P0.001). Given almost perfect intra-rater reliability, an examiner does not need to repeat ReDS measurement. Given substantial inter-rater reliability, ReDS measurements had better be measured by multiple examiners if possible.

Optimal heart rate (HR) is a promising therapeutic target in patients with heart failure with reduced ejection fraction. Nevertheless, the implication of optimal HR in patients with left ventricular assist devices (LVAD) remains unknown. The cohort included consecutive patients with sinus rhythm undergoing LVAD implantation between 2014 and 2018. Ideal HR was calculated as follows: 93 - 0.13 × (deceleration time [msec]). The impact of "HR difference," defined as an HR difference between the actual HR at discharge and the calculated ideal HR, on the 1-year mortality and heart failure readmissions was investigated. A total of 143 patients (55 years old, 101 men) was identified and tertiled considering their HR differences: (1) the optimal HR group (n = 49; HR difference27 bpm), (2) the suboptimal HR group (n = 47; HR difference = 27-42 bpm), and (3) the nonoptimal HR group; HR difference (n = 47; HR difference43 bpm). The nonoptimal HR group had a significantly higher 1-year cumulative incidence of the primary endpoint compared with the optimal HR group (38% versus 16%, P = 0.029) with a hazard ratio of 1.69 (95% confidence interval 1.02-2.57) adjusted for 6 potential confounders. In conclusion, nonoptimized HR negatively affected clinical outcomes in LVAD patients. The implication of deceleration time-guided HR optimization in LVAD patients should be further investigated.

Severe aortic stenosis sometimes accompanies advanced heart failure with reduced cardiac contractility (i.e. low-flow low-gradient aortic stenosis). The therapeutic strategy for the remaining heart failure following trans-catheter aortic valve implantation remains unknown. An 84-year-old man with six hospitalizations due to aortic stenosis and congestive heart failure with reduced ejection fraction was admitted to our institute. Heart failure remained following trans-catheter aortic valve implantation. Additional adaptive servo-ventilation therapy with optimal pressure setting determined by the ramp test further improved his heart failure symptoms. Combination therapy using trans-catheter aortic valve implantation and adaptive servo-ventilation might be a promising therapeutic tool to ameliorate heart failure with severe aortic stenosis.

Prognostic impact of heart rate reduction therapy using ivabradine, a selective inhibitor of If channel that purely reduces heart rate, in patients with heart failure with reduced ejection fraction and sinus tachycardia has been demonstrated. However, ideal heart rate remains unknown. We experienced an 80-year-old woman with reduced left ventricular ejection fraction who was hospitalized due to congestive heart failure. Following the ivabradine administration that decreased her heart rate from 100 bpm down to around 60 bpm, the “overlap” between E-wave and A-wave in the trans-mitral Doppler echocardiography diminished, accompanied by an improvement in cardiac output. Heart rate optimization targeting to diminish the overlap between E-wave and A-wave might maximize cardiac output and improve the clinical course via facilitated cardiac reverse remodeling. Further studies are warranted to validate the implication of therapeutic strategy to aggressively minimize the echocardiographic “overlap” by heart rate reduction therapy in heart failure patients.

Background: Impella is a percutaneous transcatheter left ventricular assist device. Device-related hemolysis is a serious complication that is sometimes encountered depending on the device position, device speed, and support duration. However, the impact of hemodynamics on the occurrence of hemolysis remains unknown. In this study, we aimed to clarify the relationships between hemodynamics, especially right ventricular function, and the occurrence of hemolysis during Impella-incorporated mechanical circulatory support. Methods: Consecutive patients who received Impella (2.5, CP, and 5.0) support at our institute between March 2018 and July 2021 were retrospectively included. The relationships between the pulmonary artery pulsatility index (PAPi) immediately after Impella insertion and the occurrence of hemolysis were investigated. Results: Forty-two patients (median 71 years old, 60% men) were included. Hemolysis occurred in 20 patients (48%). A cutoff of PAPi to predict hemolysis was calculated as 1.3, with 80.0% sensitivity and 72.7% specificity. Lower PAPi (

Background: Respiratory instability, which can be quantified using respiratory stability time (RST), is associated with the severity and prognostic impact of the disease in patients with chronic heart failure. However, its clinical implications in patients with severe aortic stenosis receiving transcatheter aortic valve replacement (TAVR) remain unknown. Methods: Patients who received TAVR and had paired measurements of RST at a baseline and one week following TAVR were prospectively included. Changes in RST following TAVR and its impact on post-TAVR heart failure readmissions were investigated. Results: Seventy-one patients (median age, 86 years old; 35% men) were included. The baseline RST was correlated with the severity of heart failure including elevated levels of plasma B-type natriuretic peptide (p < 0.05 for all). RST improved significantly following TAVR from 34 (26, 37) s to 36 (33, 38) s (p < 0.001). Post-TAVR lower RST (n = 18) was associated with a higher 2-year cumulative incidence of heart failure readmission (21% vs. 8%, p = 0.039) with a hazard ratio of 5.47 (95% confidence interval 0.90–33.2). Conclusion: Overall, respiratory instability improved following TAVR. Persistent respiratory instability following TAVR was associated with heart failure recurrence.

Catheter-based micro-axial ventricular assist device Impella® (Abiomed, Danvers, MA) has been used in Japanese patients with drug-refractory acute heart failure (AHF) since 2017. This is the first interim analysis of the ongoing Japan Registry for Percutaneous Ventricular Assist Device (J-PVAD) to investigate the safety and efficacy of Impella support. Between October 2017 and January 2020, 823 Japanese patients, who were treated with the Impella 2.5, CP, or 5.0 pump, were enrolled. The primary endpoints were safety profiles and cumulative 30-day survival. Among them, 44.8% of patients were acute myocardial infarction with cardiogenic shock. The Impella pumps were unable to implant in 4 patients. The Impella 2.5, CP, and 5.0 pumps were used in 72.4%, 6.2%, and 16.6%, respectively, and mean support duration was 8.1 ± 10.2 days. Combination use of Impella and venoarterial extracorporeal membrane oxygenation (VA-ECMO) was applied for 387 patients (47.3%). Pump stop occurred 22 patients (2.7%). Major adverse events included hemolysis (11.2%), hemorrhage/hematoma (6.1%), peripheral ischemia (1.6%), and stroke (1.6%). The overall 30-day survival was 62.2%. Survival of patients with single Impella support was significantly higher than patients with Impella combined with VA-ECMO support (81.1% vs 49.6%; p 0.01), who had lower blood pressure, lower left ventricular ejection fraction, and higher degree of inotropic support. Results suggest that short-term outcome of Impella support for Japanese patients was favorable with acceptable safety profiles.

The introduction of new therapeutics for patients with chronic heart failure, including sacubitril/valsartan, sodium-glucose cotransporter 2 inhibitors, and ivabradine, in addition to beta-blockers, angiotensin converting enzyme inhibitors, and mineralocorticoid receptor antagonists, lends an opportunity for significant clinical risk reduction compared to what was available just one decade ago. Further clinical options are needed, however, for patients with residual clinical congestion refractory to these therapies. Adaptive servo-ventilation is a novel therapeutic option to address significant clinical volume in cases resistant to medical therapy. The aggregate benefit of these additional therapeutic strategies in addition to foundational medical therapy may be a promising option in the selected candidates who do not achieve acceptable clinical and quality-of-life improvements with oral medical therapy alone. Now is the era to reconsider the implication of an adaptive servo-ventilation-therapy-incorporated medical therapeutic strategy for patients with congestive heart failure.

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: Sodium zirconium cyclosilicate (SZC), a newly introduced specific potassium binder, is introduced to treat hyperkalemia. However, the implications of SZC in up-titrating renin–angiotensin–aldosterone system inhibitors in patients with systolic heart failure remain unknown. Methods and Results: Patients with heart failure with left ventricular ejection fraction

Management of pulmonary congestion is a key to improve mortality and morbidity in patients with congestive heart failure, but it is often challenging due to a lack of gold standard to accurately assess the lung fluid level. We had an 86-year-old man who was admitted to our institute due to worsening congestive heart failure. His pulmonary congestion was quantified repeatedly by the novel noninvasive device, remote dielectric sensing, and was optimally managed by the medication adjustment. Remote dielectric sensing might be a promising device to quantify pulmonary congestion and guide clinicians to optimize medications in addition to the conventional multi-modalities.

BACKGROUND: Pulmonary artery pulsatility index (PAPI) is a recently proposed hemodynamic index that is associated with right ventricular function independently on volume status. However, its clinical implication in patients receiving transcatheter aortic valve replacement (TAVR) remains uninvestigated. Baseline PAPI might be a promising index that stratify patients’ clinical outcomes following TAVR. METHODS: In this retrospective cohort study, patients with severe aortic stenosis who received TAVR and completed baseline invasive hemodynamic assessments using right heart catheterization were included. The impact of baseline PAPI on the 2-year incidence of heart failure re-hospitalizations following TAVR was investigated. RESULTS: A total of 227 patients (median 86 years old, 29% men) were included. Median baseline PAPI was 3.6 (2.6, 5.5). PAPI was an independent predictor of the primary endpoint with adjusted hazard ratio of 7.01 (95% confidence interval: 2.08–23.2, P=0.008) with a cutoff of 2.1, which significantly stratified the 2-year cumulative incidence of primary endpoint (lower PAPI 21% versus high PAPI 5%, P=0.003). CONCLUSIONS: Baseline impaired right ventricular function, indicated by lower PAPI below 2.1, was associated with the occurrence of heart failure following TAVR. Further studies are warranted to clarify the mechanism underlying on our findings and the prognostic implication of aggressive intervention to improve PAPI.

We experienced a 65-year-old woman who was diagnosed as fulminant myocarditis and transferred on mechanical ventilator and veno-arterial extracorporeal membrane oxygenation (ECMO) supports. Impella 5.0 support was additionally initiated to improve pulmonary edema and unload left ventricle. We found a patent foramen ovale (PFO) at the time of Impella insertion by transesophageal echocardiography. Follow-up transesophageal echocardiography found a development of right-to-left shunt flow through PFO accompanying central hypoxia during Impella P8 support. Veno-arterial ECMO was converted to veno-arterio-venous ECMO and PFO was occluded percutaneously on the next day, which stabilized hemodynamics and systemic oxygen supply. In case of Impella 5.0 support, the existence of PFO and the development of right-to-left shunt flow should be carefully surveyed and closed immediately to maintain hemodynamics and systemic oxygen supply.

BACKGROUND Coexistent pulmonary hypertension with severe aortic stenosis confers a greater risk of mortality for patients undergoing transcatheter aortic valve replacement (TAVR). In this patient population, the impact of significant decoupling between pulmonary artery diastolic and pulmonary capillary wedge, as it relates to clinical risk, remained uncertain.Methods and Results:Patients with severe aortic stenosis who underwent TAVR and completed pre-procedural and post-procedural invasive hemodynamic assessments with right heart catheterization were retrospectively assessed. The impact of post-TAVR decoupling, defined as a pressure difference ≥3 mmHg, on 2-year all-cause mortality or risk of heart failure admission was analyzed. Among 77 included patients (median age 86 years, 23 men), 16 had post-TAVR decoupling. The existence of post-TAVR decoupling was associated with a higher cumulative incidence of the primary endpoint (44% vs. 7%, P=0.001), with an adjusted hazard ratio of 5.87 (95% confidence interval 1.58-21.9, P=0.008). CONCLUSIONS A greater risk of worse outcomes in those with post-TAVR decoupling was observed. A therapeutic strategy for post-TAVR decoupling and its clinical implication need to be created and investigated in the future.

We experienced a 39-year-old male patient who converted paracorporeal left ventricular assist device to HeartWare ventricular assist device (HVAD; Medtronic, Framingham, MA) as bridge-to-transplant indication. On the 10th postoperative day, the HVAD flow waveform presented periodical low pulsatility pattern. Significant pericardial hematoma was observed on the imaging studies, and he showed pulsus paradoxus. He was highly suspected of cardiac tamponade and performed thoracotomy. HVAD waveform might be a useful tool to monitor and early suspect of postoperative cardiac tamponade to consider more intensive examinations and thoracotomy before hemodynamic deterioration, although further large-scale studies are warranted to strengthen our hypothesis.

We encountered a 42-year-old woman with a history of diabetes mellitus and cataracts presenting with repeated syncope whose electrocardiogram showed advanced atrioventricular block. On admission, we excluded major potential differential diagnoses as causes of an atrioventricular block but did not suspect myotonic dystrophy, which was eventually diagnosed by chance based on a suspected weakness of the respiratory muscles followed by a detailed neurological physical examination. Myotonic dystrophy should be suspected as a differential diagnosis when relatively young patients present with conductance disorder.

Despite its clinical relevance, a subclass of acute decompensated heart failure (ADHF) with elevated blood pressure, known as hypertensive ADHF (HT-ADHF), has been less intensively evaluated. This study aimed to characterize the prognostic nature and pathophysiology of HT-ADHF. A total of 509 consecutive patients with first-time ADHF hospitalization were subjects of the study. Participants were divided into two groups: an HT-ADHF group (systolic blood pressure, SBP > 140 mmHg at presentation) and a non-HT-ADHF group (SBP ≤ 140 mmHg). Median follow-up duration measured 253 days. Unadjusted Kaplan-Meier analysis demonstrated both a lower cardiovascular mortality rate in the HT-ADHF group and similar incidences of heart failure rehospitalization in both groups. Adjusted Cox hazard analysis showed an association of elevated SBP at presentation with significantly lower cardiovascular mortality, though no such association was observed with heart failure rehospitalization. Moreover, elevated heart rate in combination with elevated SBP at presentation predicted a significantly lower risk of cardiovascular mortality (Hazard Ratio: 0.32, 95% CI: 0.14-0.77, P = 0.01). Also, significantly lower cardiovascular mortality was observed in this subtype, compared with other types of ADHF.

Background: The vasopressin type-2 receptor antagonist tolvaptan is an essential tool in the management of decompensated heart failure (HF) in the inpatient setting for short-term use with careful monitoring. There is conflicting evidence, however, for its long-term use. Methods and Results: In this prospective, multi-center, open-labeled, randomized control trial, Assessment of QUAlity of life during long-term treatment of ToLVaptan in refractory HF (AQUA-TLV study), patients with congestive HF refractory to furosemide ≥60 mg/day were randomly assigned to a control group or tolvaptan add-on group and followed for 6 months, after confirmation of baseline urine osmolality ≥350 mOsm/L. Twenty-nine patients (median age, 60 years; 22 male) were enrolled and assigned to a control group (n=16) or a tolvaptan group (n=13). Minnesota Living with Heart Failure Questionnaire score improved significantly in the tolvaptan group (from 58 to 10, P=0.030). In the tolvaptan group, diuretics dose reduced (P=0.001), serum creatinine decreased (P=0.040), and hyponatremia tended to improve (P=0.12). The tolvaptan group had a lower HF readmission rate compared with the control group (0.213 vs. 1.242 events/year, P=0.13). Conclusions: Six-month tolvaptan therapy improved quality of life and renal function and reduced HF readmissions, when given to the estimated responders (UMIN Clinical Trial Registry Number: UMIN 000009604).

Background: Three sodium-glucose cotransporter-2 inhibitors (SGLT2i), canagliflozin, dapagliflozin and empagliflozin, successfully reduced hospitalization for heart failure (HF) in patients with type 2 diabetes mellitus (T2DM). It remains unclear, however, whether the efficacy of the 3 SGLT2i for HF in T2DM patients is similar. Methods and Results: Eighty-one T2DM patients hospitalized due to decompensated HF were enrolled. After treatment for HF, one of the 3 SGLT2i was non-randomly used, and clinical parameters for HF and T2DM were followed for 7 days. The attending physician was allowed to adjust the dose of furosemide. No differences were observed between the 3 groups in the increase of glycosuria, or in the decreases of body weight and blood pressure 7 days after SGLT2i (interaction P>0.05). Urine volume was similarly increased on day 1, and returned to the baseline on day 7 in each group. Decrease in B-type natriuretic peptide and increase in plasma renin activity were significant in each group. Plasma aldosterone concentration, however, was significantly increased in the empagliflozin and canagliflozin groups (P

Higher B-type natriuretic peptide (BNP) levels at discharge predict higher cardiovascular events in transcatheter aortic valve implantation (TAVI) patients. However, it is not known whether the reduction in BNP levels effectively predicts prognosis. The purpose was to examine the predictive power of percentage changes in BNP levels for all-cause death and hospitalization of heart failure (HF) after TAVI in severe aortic stenosis (AS) patients. We analyzed 70 severe AS patients treated with TAVI who had a record of BNP > 200 pg/mL. Receiver operating characteristics (ROC) curves analysis for all-cause death and hospitalization for HF after TAVI revealed the cut-off percentage change in BNP, and we divided the study population into the “responder group” and the “non-responder group”. The cut-off level for the percentage change in BNP evaluated by ROC analysis was a 40% decrease in BNP (AUC = 0.733, p

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

Hemocompatibility-related adverse events (HRAEs) are substantial issues in patients with left ventricular assist devices (LVADs). Atrial fibrillation (AF) is associated with worse prognosis in patients with heart failure (HF), but its effect on HRAEs following LVAD implantation remain uncertain.Methods and Results:Data from the Japanese Mechanically Assisted Circulatory Support registry of consecutive patients who received HeartMate II LVADs and were followed for 1 year were retrospectively reviewed. Among 190 patients, 23 had AF and 167 had sinus rhythm. The AF group had comparable baseline characteristics with the non-AF group except for their higher age (53 vs. 42 years, P0.001). Following LVAD implantation, most cases of AF (73%) persisted. Antiplatelet therapy, anticoagulation therapy, and LVAD speed following LVAD implantation were comparable between groups (P0.05 for all). The 1-year survival free from HRAEs was comparable between groups (83% vs. 76%, P=0.52). Event rates of the breakdown of HRAEs were comparable between groups except for a relatively higher rate of surgically managed pump thrombosis in the AF group (0.16 vs. 0.04, incidence rate ratio 3.75, 95% confidence interval 0.87-16.1, P=0.075). These trends still remained with propensity score-matched comparison.Existence of AF had no effect on the development of HRAEs following LVAD implantation. The need to aggressively treat AF before or after LVAD implantation needs further investigation.

We recently experienced a 70-year-old woman with left main trunk-acute coronary syndrome who was initially supported by Impella 5.0 which converted to paracorporeal left ventricular assist device (LVAD) implantation as a bridge to recovery. Optimized guideline-directed medical therapy with cardiac rehabilitation resulted in successful explantation of LVAD and she discharged on foot.

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.

Tolvaptan, a vasopressin type-2 receptor antagonist, is utilized to ameliorate fluid retention following cardiac surgery. However, the optimal timing of tolvaptan administration considering novel biomarkers remains unknown. We prospectively included patients who underwent cardiac surgery between 2016 and 2020. We measured perioperative trends of free water reabsorption mediators including plasma arginine vasopressin and urine aquaporin-2. A total of 20 patients (68 [60, 75] years old, 18 men) were included. Urine volume decreased gradually after the initial 3 hours following cardiac surgery. The plasma arginine vasopressin level increased significantly with a peak at postoperative 6 hours, whereas the urine aquaporin-2 level increased later with a delayed peak at postoperative 12 hours. As a result, urine aquaporin-2 relative to the plasma arginine vasopressin level, which represents the activity of the collecting ducts and indicates predicted responses to tolvaptan, was a minimum at postoperative 6 hours. Tolvaptan administration immediately after cardiac surgery might not be recommended given the transient refractoriness to tolvaptan probably due to the stunning of kidney collecting ducts.

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: Small dense LDL-cholesterol is an established risk factor for atherosclerosis but is not routinely measured in daily practice. The association between small dense LDL-cholesterol and triglyceride, which in turn is routinely measured, in patients with acute coronary syndrome remains unknown. Methods: Consecutive patients with acute coronary syndrome who were admitted to our institute were prospectively included, and serum samples were obtained on admission. The association between small dense LDL-cholesterol and triglyceride was investigated. Results: Among 55 patients (median 71 years old, 64% men), median (interquartile range) small dense LDL-cholesterol was 23.6 (17.0, 36.0) and triglyceride was 101 (60, 134) mg/dL. Triglyceride level correlated with small dense LDL-cholesterol (r = 0.67, p &lt, 0.001) and was an independent determinant of small dense LDL-cholesterol together with body mass index (p = 0.010 and p = 0.008, respectively). Those with high triglyceride and high body mass index had a 3-fold level of small dense LDL-cholesterol compared with those with low triglyceride and low body mass index (45.8 [35.0, 54.0] mg/dL versus 15.0 [11.6, 23.7] mg/dL, p = 0.001). Conclusions: Triglyceride level was a major determinant of small dense LDL-cholesterol in patients with acute coronary syndrome. Triglyceride level might be a useful and practical biomarker for risk stratification for patients with acute coronary syndrome together with body mass index.

Ideal heart rate (HR), particularly for those with heart failure with preserved ejection fraction (HFpEF), remains unknown. We hypothesized that cardiac output would be maximum when the overlap between E-wave and A-wave at the trans-mitral flow is "zero" in the Doppler echocardiography. We retrospectively investigated the association among the overlap length between two waves, actual HR, and other echocardiographic parameters to construct a formula for estimating theoretically ideal HR among those with HFpEF. In total, 48 HFpEF patients were included (70-year-olds, 18 males). Given the results of multivariate linear regression analyses, the overlap length was estimated as follows: -1,050 + 8.4 × (HR [bpm]) + 0.6 × (deceleration time [millisecond]) + 1.7 × (A-width [millisecond]), which had a strong agreement with the actually measured overlap length (r = 0.86, P < 0.001). Theoretically ideal HR was calculated by substituting zero into the estimated overlap length as follows: 125 - 0.07 × (deceleration time [millisecond]) - 0.20 × (A-width [millisecond]). In the validation cohort including another 143 HFpEF patients, the estimated overlap using the formula again had a strong agreement with the actually measured overlap (r = 0.72, P < 0.001). In this study, we proposed a novel formula for calculating theoretically ideal HR, consisting of deceleration time and A-width, in the HFpEF cohort. Clinical implication to optimize the HR targeting the theoretically ideal HR should be investigated in prospective studies.

Management of constrictive pericarditis is often clinically challenging. Heart rate (HR) modulation using ivabradine is associated with improved clinical outcomes in patients with systolic heart failure, although it remains uninvestigated for other clinical purposes. We aimed to assess the impact of HR control in patients with constrictive pericarditis. In this retrospective study, consecutive patients who were diagnosed with constrictive pericarditis were included. Transthoracic echocardiography was performed at index discharge (day 0). The impact of HR difference between actual HR and ideal HR, which was calculated using a formula consisting of deceleration time, on heart failure readmission rates was investigated. A total of 15 patients (73 years old on median, 11 men) with constrictive pericarditis were included. On median, actual HR was 71 bpm and ideal HR was 81 bpm. Heart failure readmission rates were stratified into three groups by the HR difference: (1) optimal HR group satisfying "-10 bpm ≤ HR difference ≤ 10 bpm" (n = 4, 0.067 events per year); (2) lower HR group satisfying "HR difference-10 bpm" (n = 7, 0.118 events per year, incidence rate ratio 1.98, 95% confidence interval 0.06-61.6); (3) higher HR group satisfying "HR difference10 bpm" (n = 4, 0.231 events per year, incidence rate ratio 9.22, 95% confidence interval 0.36-237.8). In conclusion, non-optimized HR was associated with an increased risk of heart failure recurrence in patients with constrictive pericarditis. Prospective assessment of deceleration time-guided HR optimization in patients with constrictive pericarditis is needed.

Baseline and post-procedural elevations in serum troponin-T levels are associated with increased morbidity and mortality following transcatheter aortic valve replacement (TAVR). However, the prognostic impact of change in serum troponin-T level following TAVR remains unknown.Among the patients with severe aortic stenosis who underwent TAVR, those with baseline serum troponin-T level ≥51.5 ng/L were excluded. The impact of increases in serum troponin-T level to an abnormally high range (≥51.5 ng/L) following TAVR on 2-year cardiovascular death or heart failure readmissions was investigated.Among 189 included patients (median 86 years old, 28% men), serum troponin-T level increased in 79 patients following TAVR. An increase in serum troponin-T was associated with a higher rate of 30-day adverse events, predominantly due to pacemaker implantation for complete atrio-ventricular block, and a higher 2-year cumulative incidence of the primary endpoint (hazard ratio 5.24, 95% confidence interval 1.64-16.8, p = 0.005) adjusted for the potential confounders.Post-procedural increase in serum troponin-T level was associated with adverse clinical outcomes following TAVR.

Hyperkalemia is a challenging comorbidity to manage in patients with heart failure and chronic kidney disease, particularly when administering renin-angiotensin-aldosterone system inhibitors. We encountered an 88-year-old woman with hypertensive heart failure and chronic kidney disease. A mineralocorticoid receptor antagonist was able to be safely administered despite persistent hyperkalemia when sodium zirconium cyclosilicate, a non-absorbed, non-polymer zirconium silicate compound that preferentially exchanges hydrogen and sodium for potassium and ammonium ions in the gastrointestinal tract, was concomitantly administered. Sodium zirconium cyclosilicate might be a promising therapeutic tool to use in order to administer mineralocorticoid receptor antagonist safely in patients with heart failure, chronic kidney disease, and hyperkalemia.

Background: The effects of mineralocorticoid receptor antagonists, including the newly introduced esaxerenone, on renal function remain uncertain. Methods and Results: This retrospective study was performed on patients who received esaxerenone for resistant hypertension between November 2019 and June 2020. Trends in the estimated glomerular filtration rate (eGFR) were compared between the 6-month period before esaxerenone treatment (pre-treatment period) and the 6-month treatment period on esaxerenone. Twenty-six patients (15 men), with a median age of 70 years (interquartile range [IQR] 51–73 years) and a median systolic blood pressure of 146 mmHg (IQR 139–156 mmHg), were included in the study and completed 6 months of esaxerenone therapy without any adverse events. eGFR decreased significantly during the pre-treatment period (from 66.6 to 59.5 mL/min/1.73 m2; P=0.003), whereas eGFR was unchanged during the treatment period (from 59.5 to 61.8 mL/min/1.73 m2; P=0.15). The median change in eGFR differed significantly between the treatment and pre-treatment periods (3.8 [IQR −4.2, 6.8] vs. −6.1 [IQR −11.1, 1.8] mL/min/1.73 m2, respectively; P=0.008). Conclusions: Esaxerenone may have renoprotective effects when administered to treat hypertension. Further studies are needed to understand which patient populations may see greater renoprotective benefits with esaxerenone.

Background Mortality following transcatheter aortic valve replacement (TAVR) in patients with post-procedural left ventricular systolic dysfunction remains high. We investigated clinical variables associating with worse clinical outcomes following TAVR in patients with systolic dysfunction. Methods We retrospectively investigated 2588 patients with severe aortic stenosis who received TAVR and were enrolled in the optimized transcatheter valvular intervention (OCEAN-TAVI) multicenter registry (UMIN000020423). The association between the clinical variables following TAVR and 2-year cardiovascular mortality was investigated among those with post-TAVR left ventricular ejection fraction less than 50%. Results A total of 298 patients (median 85 years old, 131 men) were included. The presence of moderate or greater tricuspid regurgitation following TAVR was independently associated with 2-year mortality (adjusted hazard ratio 3.41, 95% confidence interval 1.15-10.1), and significantly discriminated 2-year cardiovascular mortality (30% vs. 12%, p = 0.001). No patients with any improvement in tricuspid regurgitation had cardiovascular death. Conclusion Following TAVR, the existence of significant tricuspid regurgitation was associated with cardiovascular mortality in patients with heart failure with reduced ejection fraction.