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The therapeutic strategy for sustained ventricular tachycardia (VT) during left ventricular assist device usage remains unclear. We encountered a patient with durable left ventricular assist device who presented sustained VT. Electrophysiological mapping was able to be established appropriately owing to the robust mechanical hemodynamics support despite inter-device interference. The three-dimensional activation map of clinically documented VT demonstrated that the propagation exited from the right ventricular apex through the critical isthmus located at the epicardium or interventricular septum, which was successfully treated by catheter ablation at the exit site. Further experiences like ours should be accumulated to establish a therapeutic strategy.

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

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and its prevalence increases with age. AF causes palpitations, heart failure, and cardiogenic embolism. Of them, the most critical and fatal complication is a cardio-embolic event. Oral anticoagulation plays a central role in reducing stroke risk in AF patients. Recently, when oral anticoagulation is considered in patients with non-valvular AF who are eligible for direct oral coagulations, they are preferred to vitamin K antagonist based on accumulating evidence. Although many patients can tolerate oral anticoagulation, there is a subset of patients who cannot tolerate long-term oral anticoagulation. Such a subset has a higher bleeding risk as indicated by the HAS-BLED score under oral anticoagulation. This subset of patients requires effective and safe non-pharmacological alternative therapies for stroke prevention. One of the promising non-pharmacological therapies is left atrial appendage closure. Three randomized controlled trials demonstrated non-inferiority of percutaneous left atrial appendage closure using WATCHMAN family to oral anticoagulation (Boston Scientific, Marlborough, MA, USA). WATCHMAN FLX, which was innovated following WATCHMAN 2.5, was associated with fewer safety events and a higher success rate of effective appendage closure. Nevertheless, several unsolved issues remain, including device-related thrombosis, post-treatment antithrombotic therapy, and peri-device leakage. Left atrial appendage closure for patients with non-valvular AF may be an alternative therapy to avoid cardiac embolism for high bleeding risk patients with contraindications to long-term oral anticoagulation therapy.

Objectives: Six months after withdrawal of the HeartWare HVAD System (HVAD; Medtronic) from sale, approximately 4000 patients continue ongoing support with this device. In light of the diminishing experience, this global consensus document summarizes key management recommendations. Methods: International experts with experience in the management of patients with ongoing HVAD support were invited to summarize key aspects of patient and pump management and highlight differences in the current HeartMate 3 (Abbott Laboratories) ventricular assist device. Clinicians from high-implanting HVAD sites reviewed current literature and reported experience to generate a consensus statement. Results: Specific guidelines to assist in the management of ongoing HVAD patients are developed. Key management protocols and helpful techniques developed from experienced clinicians are combined into a short guideline document. As experience with HeartMate 3 increases, key differences in approach to management are highlighted, where appropriate. Conclusions: With decreasing worldwide experience in the ongoing management of HVAD-supported patients, this consensus guideline provides a summary of best practice techniques from international centers. Differences in HeartMate 3 management are highlighted.

Cardio-renal syndrome is a challenging clinical entity to manage, and is often associated with increased morbidity and mortality. We hypothesized that adaptive servo-ventilation (ASV), non-invasive positive pressure ventilation that ameliorates systemic/pulmonary congestion, may improve renal function in patients with symptomatic heart failure complicated by the cardio-renal syndrome. Patients with symptomatic congestive heart failure who underwent ASV therapy for over 1 month were included in this retrospective study. The trajectory of the estimated glomerular filtration ratio (eGFR) between the pre-1 month period and the post-one-month period (on ASV) were compared. A total of 81 patients (median 65 years old, 65 men) were included. eGFR decreased during the pre-1 month period from 52.7 (41.7, 64.6) down to 49.9 (37.3, 63.5) mL/minute/1.73 m2 (P < 0.001) whereas we observed an increase following one-month of ASV therapy up to 53.4 (38.6, 68.6) mL/minute/1.73 m2 (P = 0.022). A reduction in furosemide equivalent dose following the initiation of ASV therapy was independently associated with increases in eGFR with an adjusted odds ratio of 13.72 (95% confidence interval 3.40-55.3, P < 0.001). In conclusion, short-term ASV therapy was associated with the preservation of renal function, particularly when the dose of loop diuretics was concomitantly reduced.

Destination therapy (DT) is the indication to implant a left ventricular assist device (LVAD) in a patient with stage D heart failure who is not a candidate for heart transplantation. The implantable LVAD has been utilized in Japan since 2011 under the indication of bridge to transplant (BTT). After almost 10 year lag, DT has finally been approved and reimbursed in May 2021 in Japan. To initiate the DT program in Japan, revision of the LVAD indication from BTT is necessary. Also, in-depth discussion of caregiver issues as well as end-of-life care is indispensable. For that purpose, we assembled a DT committee of multidisciplinary members in August 2020, and started monthly discussions via web-based communication during the COVID-19 pandemic. This is a summary of the consensus reached after 6 months' discussion, and we have included as many relevant topics as possible. Clinical application of DT has just started, and we are willing to revise this consensus to meet the forthcoming issues raised during real-world clinical experience.

Background: Although many risk factors have been reported to be associated with poor clinical outcomes following transcatheter aortic valve replacement (TAVR), the implications of inadequate cardiac unloading following TAVR remain unknown. We investigated the prognostic impact of inadequate cardiac unloading following TAVR. Methods and Results: We retrospectively analyzed a cohort of patients with severe aortic stenosis who underwent invasive hemodynamic assessment following TAVR. The impact of inadequate cardiac unloading, defined as an elevated pulmonary capillary wedge pressure (PCWP), on the composite primary endpoint of cardiovascular mortality or heart failure readmission was investigated. Eighty-two patients (median age 86 years; 57 women) were included. Median PCWP following TAVR was 9 mmHg (interquartile range 7-13 mmHg). A higher PCWP tended to be associated with an increased risk of adverse cardiovascular events (adjusted hazard ratio 1.18; 95% confidence interval 0.99-1.41). A cut-off value of PCWP >12 mmHg, calculated by time-dependent receiver operating characteristics analysis, stratified the cumulative incidence of the primary endpoint (2-year incidence of 36% vs. 8%). Uptitration of the diuretic dose was associated with event freedom among those with PCWP >12 mmHg. Conclusions: Inadequate cardiac unloading following TAVR was associated with an increased risk of adverse clinical events. Uptitration of medical therapies to improve cardiac hemodynamics after TAVR may reduce this risk.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) reduces mortality and morbidity in patients with chronic heart failure (HF). However, the clinical implication of SGLT2i therapy in patients with acute decompensated HF remains uncertain. We prospectively studied 86 type 2 diabetic mellitus (T2DM) patients (71.8 ± 12.1 years, 55 men) who were hospitalized for acute decompensated HF and received SGLT2i during the index hospitalization. Among the patients, 56 continued SGLT2i at discharge and 30 did not. The continued group experienced fewer HF re-hospitalizations than the discontinued group (24% versus 39%, P = 0.008) with a hazard ratio of 0.29 (95% confidence interval 0.10-0.85) adjusted for other significant potential confounders. In conclusion, long-term SGLT2i therapy might prevent unplanned HF re-hospitalization in patients with T2DM and acute decompensated HF.

Heart rate modulation therapy using ivabradine improves mortality and morbidity in patients with systolic dysfunction. However, a target heart rate remains uncertain. Echocardiography-guided ivabradine therapy, in which we attempt to approach zero overlap between two diastolic filling inflow waves, has recently been proposed to maximize cardiac output, facilitate reverse remodeling, and reduce mortality and morbidity, instead of using an absolute value for the target heart rate. Prospective studies are needed to validate the clinical implication of these therapeutic strategies. Also, this concept should be expanded to other clinical scenarios.

The DAPA-HF trial demonstrated that sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced worsening heart failure (HF) events in chronic HF patients with or without type 2 diabetic mellitus (T2DM). However, it remains unclear whether the effectiveness of SGLT2i is also observed in patients with decompensated HF irrespective of HbA1c level. Eighty-one T2DM patients hospitalized due to decompensated HF were enrolled and divided into 2 groups according to their HbA1c levels (group H, HbA1c 6.9-13.0%, n = 41; group L, HbA1c < 6.9%, n = 40). After the initial management of HF, one of the SGLT2i (canagliflozin 100 mg/day or dapagliflozin 5 mg/day or empagliflozin 10 mg/day) was non-randomly administered, and clinical parameters associating with HF and T2DM were followed for 7 days. No symptomatic hypoglycemia was observed in any patient. In both groups, urine glucose excretion was increased significantly after the administration of SGLT2i. However, its amount was greater in group H than group L. Urine volume was increased significantly at day 1 in both groups. Urine volume returned to the baseline after one week in group L. In contrast, the increase in urine volume persisted at least for one week in group H. Of note, a decrease in B-type natriuretic peptide levels after the initiation of SGLT2i was observed in both groups similarly despite differences in urine output and excretion of urine glucose. In conclusion, SGLT2i can improve decompensated HF in patients with T2DM irrespective of the HbA1c level.

Background Sodium zirconium cyclosilicate (SZC), a newly‐developed selective potassium binder, has been clinically available to treat hyperkalemia. SZC might be a promising option to manage hyperkalemia, particularly in patients with heart failure, who often require potassium‐sparing medications. However, the optimal initial dose of SZC therapy at a loading dose (30 g per day for the initial 2 days) versus a maintenance dose (5 g per day) remains unknown. Methods Consecutive patients with heart failure and hyperkalemia who received 2‐day SZC therapy were retrospectively included. Safety and efficacy of SZC therapy were compared between the two strategies (maintenance versus loading). Results We had 16 patients (76 years old, 11 men) who received 2‐day SZC therapy (4 maintenance dose group and 12 loading dose group). Serum potassium decreased 0.7 mEqL/L by 2‐day maintenance dose therapy and 1.3 mEq/L by 2‐day loading dose therapy. Following 2‐day SZC therapy, 25% of patients had hypokalemia, which was defined as serum potassium

We sometimes encounter patients with systolic heart failure and cardiac amyloidosis. Neurohormonal blockers are guideline-directed medical therapy for those with systolic heart failure. However, its implication among the above cohort remains controversial. Of 3 patients with systolic heart failure and cardiac amyloidosis who we encountered, cardiac reverse remodeling was achieved in 2 patients who received neurohormonal blockers, whereas cardiac function remained unchanged in a patient not receiving neurohormonal blockers. Neurohormonal blockers might be keys to achieve cardiac reverse remodeling and favorable clinical outcomes even in patients with systolic heart failure and cardiac amyloidosis, although further larger-scale studies are required to validate our hypothesis.

Severe aortic stenosis (AS) is often accompanied by renal dysfunction, which portends a poor prognosis. Trans-catheter aortic valve replacement (TAVR) is an accepted therapy for patients with severe AS, whereas the prediction of persistent renal dysfunction following TAVR remains challenging. In this study, we aimed to evaluate the pre-procedural score to assess the reversibility of renal dysfunction following TAVR. A total of 2,588 patients with severe AS who received TAVR and were enrolled in the Optimized transCathEter vAlvular iNtervention (OCEAN-TAVI) multicenter registry (UMIN000020423) were retrospectively investigated and those with serum creatinine (Cre) data at baseline and one year following TAVR were included. The Cre score was calculated using the formula: 0.2 × (age [years]) + 3.6 × (baseline serum Cre [mg/dL]). This score was evaluated to assess the risk of persistent renal dysfunction defined as serum Cre level > 1.5 mg/dL at one year following TAVR. Of the 1705 patients (84.3 ± 5.0 years old) included, 246 (14%) had persistent renal dysfunction following TAVR. The Cre score predicted the incidence of persistent renal dysfunction with an adjusted incidence rate ratio of 1.48 (95% confidence interval 1.42-1.56) with a cutoff of 21.4 (43% versus 5%, P < 0.001). The Cre score also predicted 4-year survival following TAVR (70% versus 52%, P < 0.001) with an adjusted hazard ratio of 1.75 (95% confidence interval 1.29-2.37). In conclusion, the Cre score identified those with a high risk of one-year persistent renal dysfunction following TAVR. The implication of Cre score-guided therapeutic strategy is the next concern.

Background: Patients with anemia have a poor prognosis following transcatheter aortic valve implantation (TAVI). Given the unique distribution of hemoglobin levels in the Japanese cohort, the optimal cut-off hemoglobin value may help stratify Japanese patients’ mortality following TAVI. Methods and Results: Data of patients who underwent TAVI were collected from the prospective multicenter Optimized transCathEter vAlvular iNtervention (OCEAN)-TAVI Registry. Receiver operating characteristic analysis was used to calculate a hemoglobin cut-off value to stratify 2-year mortality following TAVI. In all, 2,588 patients (mean [±SD] age 84.4±5.2 years, 795 men) were included in the study. Of these patients, 909 (35.1%) had anemia, which was defined as hemoglobin

We had a 72-year-old man with advanced gastric cancer, poorly differentiated adenocarcinoma, receiving chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) plus oxaliplatin. Ascites developed despite remission of gastric cancer and metastasis. Given no malignant cells in ascites, leg edema, renal impairment, hypoalbuminemia, and massive proteinuria, we diagnosed as nephrotic syndrome with microscopic hematuria. Renal biopsy showed membranoproliferative glomerulonephritis with no deposition of immunoglobulins and complements. Of note, electronic microscopy found organized deposits with microtubular structures in the glomerular capillary lumens and subendothelial spaces. The liquid chromatography-tandem mass spectrometry method detected fibrinogen alpha chain, beta chain, gamma chain, and fibronectin, and we eventually diagnosed cryofibrinogen-associated glomerulonephritis. Cryofibrinogen was not detected in plasma. He was expired at 5 months following renal biopsy due to the progression of refractory nephrotic syndrome. In addition to the detailed assessment of specifically organized deposits, the analysis using liquid chromatography-tandem mass spectrometry method is useful to diagnose cryofibrinogen-associated glomerulonephritis. We should consider cryofibrinogen-associated glomerulonephritis as a differential diagnosis when the patients with malignancy showed abnormal urinalysis and renal impairment, though it is a rare disease.

Malignant lymphoma is rarely complicated by secondary IgA nephropathy. We encountered a 74-year-old man with rapidly progressive glomerulonephritis due to IgA nephropathy with predominant deposition of IgA2, instead of IgA1, in the glomerulus that was eventually diagnosed as secondary IgA nephropathy due to mantle cell lymphoma. Renal impairment was improved by chemotherapy for the mantle cell lymphoma. IgA came from the colonic mucosa that was stimulated by the infiltrated lymphoma cells, instead of the tumor itself. We should consider mantle cell lymphoma as a cause of secondary IgA nephropathy, although its prevalence may not be very high.

We experienced a 78-year-old woman who was diagnosed with hereditary transthyretin cardiac amyloidosis and administered patisiran for advanced heart failure refractory to tafamidis. The levels of N-terminal pro B-type natriuretic peptide and left ventricular mass index decreased following the six-month patisiran treatment without any complications. Patisiran might be a promising disease-modifying drug for hereditary transthyretin cardiac amyloidosis even in its advanced stage, although further evaluation in a large cohort is warranted.

Background Secondary mitral regurgitation (SMR) is a major comorbidity in patients with heart failure with reduced ejection fraction (HFrEF). Transcatheter edge-to-edge repair (TEER) using the MitraClip™ system is a promising tool for selected patients with SMR and HFrEF. Durable success using this system in patients who have advanced heart failure and unsuitable anatomy remains a clinical challenge. Case summary Three patients aged 67–72 years with HFrEF on inotropic support successfully underwent Impella®-assisted TEER at our centre. Following the procedure, two patients were able to be weaned off inotropic support and were discharged, while one patient expired during the index hospitalization. Discussion Impella®-assisted TEER may be a feasible strategy for patients with SMR and HFrEF with unstable haemodynamics particularly when cardiac replacement therapy is not applicable.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce the risk of hospitalization for heart failure (HF) or death from cardiovascular causes among patients with chronic HF. However, little is known about the specific factors associated with clinical events during SGLT2i therapy in patients hospitalized for acute decompensated heart failure (ADHF). Methods: Consecutive patients who were hospitalized for ADHF and received SGLT2i during the index hospitalization between February 2016 and April 2021 were retrospectively evaluated. We investigated the factors associated with recurrent hospitalization for HF during the SGLT2i therapy. Results: A total of 143 patients (median age 73 years, 92 men) were included. Estimated glomerular filtration rate (eGFR) was negatively associated with a primary endpoint with a hazard ratio of 0.94 (95% confidence interval 0.90–0.98, p = 0.007). Those with lower eGFR < 40.9 mL/min/1.73 m2 (n = 47) had significantly lower freedom from HF hospitalization during 1-year therapeutic period (73% versus 94%, p = 0.005). Conclusions: Among patients who initiated medical therapy incorporating SGLT2i during the hospitalization for ADHF, a lower eGFR at baseline was associated with a recurrent hospitalization for HF. Early administration of SGLT2i prior to deterioration of renal function would be highly recommended to enjoy greater benefit from SGLT2i.

Background: Sodium zirconium cyclosilicate (SZC), a newly introduced potassium binder, is indicated for treating hyperkalemia. SZC-incorporated up-titration of renin-angiotensin system inhibitors and mineralocorticoid receptor antagonists has been recommended for those with systolic heart failure, whereas SZC is often terminated following the improvement of hyperkalemia in real-world practice. We aimed to investigate the impact of SZC cessation on the recurrence of hyperkalemia. Methods: Patients with systolic heart failure, in whom SZC was discontinued following improvement in hyperkalemia, were studied and compared to those who had continued SZC. All patients were followed for one year or until August 2022. The recurrent rates of hyperkalemia were compared between the two groups. Results: A total of 30 patients (median age 83 years, 53% men, median left ventricular ejection fraction 42%) were included. The one-year cumulative incidence of recurrent hyperkalemia was 93% in the group who discontinued SZC versus 22% in those who continued SZC (p = 0.032). In the group where SZC was withdrawn, doses of renin-angiotensin system inhibitors and mineralocorticoid receptor antagonists were less up-titrated, echocardiographic evidence of reverse remodeling occurred less, and readmission due to worsening heart failure tended to be higher compared to those who remained on SZC therapy. Conclusions: SZC cessation was associated with recurrent hyperkalemia and suboptimal medical therapy optimization compared to continuation of SZC therapy.

The impact of tolvaptan on the long-term outcomes of patients with heart failure (HF) remains inconclusive. We evaluated patients requiring long-term congestion management for the time to rehospitalization for HF (HF rehospitalization), the time to in-hospital death and explored the factors that may influence the outcomes.Using data (April 2008 to September 2019) from a medical claims database, patients with HF prescribed tolvaptan (tolvaptan cohort) and those prescribed loop diuretics before tolvaptan was introduced to the hospital (furosemide cohort) were compared. Patients with HF who experienced ≥2 HF hospitalizations and ≥ 1 tolvaptan or loop diuretic prescription during and after HF hospitalization were included. Data of patients with serum creatinine and estimated glomerular filtration rate were analyzed for time to HF rehospitalization and in-hospital death within 1 year after the second discharge and factors that may influence the outcomes.Among the 1931 and 631 tolvaptan and furosemide cohort patients, respectively, time to HF rehospitalization was not significantly different (p = 0.0921); time to in-hospital death was significantly longer in the tolvaptan cohort than in the furosemide cohort (p = 0.0005). Age, serum sodium, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were identified as factors for both outcomes (p 0.05).Tolvaptan did not significantly affect time to HF rehospitalization. However, further worsening of the condition leading to death may be delayed, and time to in-hospital death may be prolonged in patients treated with tolvaptan, indicating its usefulness for long-term congestion management.

Remote dielectric sensing (ReDS) is a novel, non-invasive, miniature radar based, and vest testing system to quantify pulmonary edema. ReDS value can represent valuable additions to the fluid management in patients with congestive heart failure. We report a case of relatively lower ReDS value in spite of the obvious clinical volume overload and pulmonary congestion in a patient with acute heart failure and chronic obstructive pulmonary disease. Treatment for congestion to ameliorate his heart failure was accompanied by further decrease in ReDS value below normal ranges. Although ReDS technology is a promising modality to quantify the lung fluid amount, we might have to pay attention to some unique comorbidities including chronic obstructive pulmonary disease, which might attenuate electromagnetic waves and let ReDS values become inappropriately lower. LEARNING OBJECTIVE: Remote dielectric sensing (ReDS) is a novel, non-invasive, miniature radar based, and vest testing system to detect pulmonary edema, which has a robust correlation with pulmonary fluid content in heart failure patients. However, the applicability of this modality in patients with a variety of comorbidities remains unknown. We should pay attention to unique comorbidities including chronic obstructive pulmonary disease, which might attenuate electromagnetic waves and let ReDS values become inappropriately lower.

Elevated serum angiopoietin-2 levels in patients with acute myocardial infarction-related cardiogenic shock with and without intra-aortic balloon pump as well as acute decompensated heart failure are associated with short-term mortality. However, its prognostic impact in patients with cardiogenic shock supported by Impella-incorporated mechanical circulatory support (MCS) remains unknown. Patients who received temporary MCS (Impella alone or Impella and veno-arterial extracorporeal membrane oxygenation) in our institute between August 2018 and January 2022 were included in this prospective study. The serum levels of angiopoietin-2 were measured just before and following the initiation of temporary MCS therapy. Association between the levels of serum angiopoietin-2 and 30-day mortality was investigated. A total of 38 patients (median 72 years old, 63% men) were included. The median levels of serum angiopoetin-2 tended to decrease from baseline to 4 days following the initiation of temporary MCS from 5.2 (3.3, 10.5) ng/mL to 4.8 (2.7, 6.8) ng/mL (p = 0.132). A higher angiopoietin-2 ( 6.8 ng/mL) following the initiation of temporary MCS was associated with higher 30-day mortality (89.7% versus 44.4%, p = 0.0048) with an odds ratio 18.946 (95% confidence interval 1.624-218.695, p = 0.018) adjusted for potential confounders. A higher serum angiopoietin-2 level following the initiation of Impella-incorporated temporary MCS, instead of baseline angiopoetin-2 level, was associated with higher short-term mortality.

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors might improve renal anemia maintaining fewer cardiovascular complications. However, its safety and efficacy, as well as its impact on inflammatory biomarkers, in heart failure patients remain unknown. We initiated HIF-PH inhibitors in 13 patients with chronic heart failure and renal anemia (median age 77 years, median estimated glomerular filtration rate 24.9 mL/min/1.73m

BACKGROUND Optimal patient selection and device pressure settings are key to successful adaptive servo-ventilation therapy, but there is no established strategy thus far. Adaptive servo-ventilation therapy at an inappropriately high pressure setting for those without pulmonary congestion decreases cardiac output and worsens clinical outcomes. The remote dielectric sensing system (ReDS) is a novel noninvasive tool to estimate the lung fluid amount. The ReDS might be a promising tool for successful adaptive servo-ventilation therapy if appropriately utilized for optimal patient selection and device pressure setting. CASE REPORT An 83-year-old woman was admitted to our hospital to treat acute decompensated heart failure with preserved ejection fraction that was refractory to conventional medical therapy. Following the confirmation that she had significant pulmonary congestion with 47% of the ReDS value (normal range, 20-35%), we performed a "ramp test" to optimize device pressure, by measuring ReDS values and noninvasively estimating the cardiac output and stroke volume at each pressure setting. The device pressure setting was finally determined to minimize pulmonary congestion and maximize cardiac output. Following the continuous adaptive servo-ventilation therapy with the optimized pressure setting, the patient's hospitalization was uneventful and she was discharged. CONCLUSIONS We propose performing a ramp test to optimize the pressure setting of adaptive servo-ventilation by utilizing ReDS technology for each patient, instead of using a default or inappropriately higher pressure setting. However, further studies including large patient populations are warranted to validate the prognostic implication of this customized ramp test protocol.

Urine cyclic adenosine monophosphate (cAMP) is a biomarker to assess the residual function of the collecting duct in the kidney. Prognostic implication of urine cAMP levels in patients with chronic kidney disease (CKD) remains unknown.Patients who were followed at our specific outpatient clinic to treat their CKD between December 2015 and December 2019 were included in this prospective study. The impact of urine cAMP levels on the composite of dialysis administration, cardiovascular death, and doubling of serum creatinine concentration was investigated.A total of 106 patients (median 72 years old, 80 men, and median estimated glomerular filtration rate 28.4 mL/min/1.73 mA lower urine cAMP is an independent predictor of renal deterioration and cardiovascular death in patients with CKD.

Titration of beta-blockers is a gold-standard therapy in patients with heart failure and a reduced ejection fraction but is sometimes challenging to administer, given symptomatic hypotension. Ivabradine is a recently introduced selective If channel inhibitor that purely reduces the heart rate. We encountered a patient with advanced heart failure in whom a beta-blocker could not be up-titrated given his symptomatic hypotension. Following the initiation of ivabradine, an increase in blood pressure due to heart rate optimization, probably via an improvement in the cardiac output, allowed for the further up-titration of carvedilol, followed by a successful clinical course. Ivabradine might be a novel therapeutic tool to facilitate the up-titration of beta-blockers in patients with heart failure and hypotension.

Heart rate reduction therapy using ivabradine has demonstrated its prognostic implication in patients with heart failure with reduced ejection fraction. However, the target heart rate with optimal clinical outcomes, particularly for those with systolic dysfunction following a transcatheter aortic valve replacement (TAVR), remains unknown. Consecutive patients with left ventricular ejection fraction (LVEF) < 50% and sinus rhythm following TAVR received transthoracic echocardiography at index discharge. The ideal heart rate was calculated using a formula: 93 - 0.13 × (deceleration time [ms]). Those whose actual heart rates at discharge were within 10 bpm of the calculated ideal heart rate were assigned to the optimal heart rate group, and their prognosis was compared with those without. Twenty-four patients (83 [78, 85] years old, LVEF 41% [35%, 44%], 16 males) were included. The median difference between actual heart rate and ideal heart rate was 12 (0, 16) bpm and 11 patients were assigned to the optimal heart rate group. One year later, the optimal heart rate group achieved more improvement in LVEF (24% [15%, 28%] vs. 7% [7%, 12%], p = .003) and had lower heart failure readmission rates (0.059 vs. 0.116 events/year; p = .49). In conclusion, an optimal heart rate might be associated with cardiac reverse remodeling and prevention of heart failure recurrences in patients with systolic dysfunction following TAVR. The implication of deceleration time-guided heart rate optimization therapy for such cohorts remains the next concern.

A 54-year-old man was admitted to our institute with a diagnosis of infectious endocarditis with vegetation on the mitral valve and severe regurgitation due to Gemella morbillorum infection together with renal dysfunction, which was eventually diagnosed as infection-related pauci-immune necrotizing crescentic glomerulonephritis. Given the refractoriness to antibiotics, the persistent activity of nephritis, and repeated cerebral hemorrhaging, we prioritized steroid therapy over early surgical mitral valve replacement. Following steroid therapy, the glomerulonephritis completely improved. Although the administration of steroid therapy in the active phase of infectious endocarditis remains controversial, it might be indicated if comorbid glomerulonephritis is critical.

An 83-year-old woman with a 1-year history of scheduled intravitreal injection of vascular endothelial growth factor inhibitor (aflibercept) was diagnosed with nephrotic syndrome due to focal segmental glomerulosclerosis with histopathological findings of segmental infiltration of foam cells in the glomerular capillaries. Her nephrotic syndrome improved immediately following the termination of aflibercept intravitreal injection without steroid therapy. Although widely used to treat ophthalmic diseases, we should keep in mind that even intravitreal injection of vascular endothelial growth factor inhibitor, as opposed to systemic administration, can cause kidney injury.

The patient was a 59-year-old female with advanced heart failure and severe functional mitral regurgitation who was classified as INTERMACS profile 4 with repeated hospitalizations despite guideline-directed medical therapy. She was also listed for heart transplantation. After comparing the two major therapeutic strategies: (1) durable left ventricular assist device (LVAD) implantation and (2) percutaneous MitraClip procedure (Abbott Vascular, Abbott Park, IL, USA), we eventually decided to proceed with MitraClip, given her relatively lower B-type natriuretic peptide, lower MAGGIC Heart Failure risk score, and higher predicted survival without LVAD. The post-procedural course was favorable without any comorbidities or worsening of heart failure for 10 months. A diagnostic paradigm to guide which strategy to choose (LVAD or MitraClip) for patients with advanced heart failure and functional mitral regurgitation should be constructed.

Background The safety and efficacy of MitraClip for advanced heart failure (HF) patients who are inotrope-dependent or mechanically supported are unknown. Case summary The patient was a 71-year-old man diagnosed as dilated cardiomyopathy in 2003. He was admitted due to worsening HF in January 2019 and became dependent upon intravenous infusion of inotropes. During the 8-month hospitalization, his haemodynamics were relatively static with bed rest and continuous inotropes, but he was definitely dependent on them. Our multidisciplinary team decided to perform both cardiac resynchronization therapy (CRT) and MitraClip under Impella support. First, Impella was inserted from left subclavian artery. After a week, CRT was implanted from right subclavian vein, and the QRS duration of electrocardiogram became remarkably narrow. MitraClip was performed 2 weeks after Impella, and functional mitral regurgitation improved from severe to mild, and Impella was removed on the same day. Inotropes could be ceased, and he was discharged 2 months after MitraClip. Discussion During inotrope-dependent status, there was a risk that HF would worsen with haemodynamic collapse when performing CRT implantation, and we firstly supported his haemodynamics by Impella. Cardiac resynchronization therapy implantation before MitraClip seemed to be crucial. In fact, the mitral valve morphology before Impella insertion had very poor coaptation of the anterior and posterior leaflets that was not optimal for MitraClip procedure. But the Impella support and correction of dyssynchrony by CRT markedly improved the coaptation of those leaflets. The combination therapy of CRT and MitraClip unloading with Impella maybe a new therapeutic option for advanced HF.

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.

A 76-year-old woman had received surgical mitral valve replacement with Magna Mitral Ease (Edwards Lifesciences, Irvine, CA, USA) 25 mm for functional severe mitral regurgitation 6 years previously. She presented recurrence of heart failure due to severe stenotic and moderate regurgitant degeneration of the implanted mitral bioprosthesis. Considering her comorbidities and left ventricular systolic dysfunction, our heart valve team eventually decided to perform percutaneous transseptal transcatheter mitral valve-in-valve replacement instead of surgical redo mitral valve replacement, using a 26 mm SAPIEN 3 valve (Edwards Lifesciences) via trans-femoral approach. Post-procedural course was uneventful and she was discharged on post-procedural day 2. This is, to the best of our knowledge, the first case of successful percutaneous transseptal transcatheter mitral valve-in-valve replacement in Japan. Further large-scale prospective studies are warranted to validate its long-term safety and efficacy, particularly by comparing with the redo surgery.

Tolvaptan, a vasopressin type-2 receptor antagonist, is indicated for fluid retention. It is considered that the response to tolvaptan reduces as renal function deteriorates, whereas we sometimes experience “non-responders” to tolvaptan despite well-preserved renal function. While the expression of aquaporin-2 might be a key to response to tolvaptan, detailed mechanism of refractoriness to tolvaptan remains unknown. We experienced two patients with congestive heart failure and diabetic nephropathy, in whom the responses to tolvaptan were uniquely opposite. In one case, immunohistochemical staining showed expression of aquaporin-2 in the collecting duct despite severely reduced renal function, followed by the good response to tolvaptan with increased urine output. In another case, immunohistochemical staining showed absence of aquaporin-2 with infiltration of inflammatory cells in the kidney medulla despite relatively preserved renal function, followed by refractoriness to tolvaptan without any increase in urine output. Inactivated aquaporin-2 expression in the collecting duct, which was for example caused by pre-clinical urinary infection as our latter case, might have an association with refractoriness to tolvaptan.

Patients with advanced heart failure often accompany severe function mitral regurgitation refractory to optimal medical therapy. Degenerative mitral regurgitation also develops due to various degeneration of mitral valve. Surgical intervention to the mitral valve might be effective in some cases, but it is challenging for the high-risk cases. Recently, percutaneous edge-to-edge mitral valve repair using the MitraClip system, which enables us to approach the mitral valve at relatively low risk, has developed. Two major prospective randomized control trials have been conducted to investigate the clinical advantage of MitraClip system over optimal medical therapy in patients with severe mitral regurgitation; both showed controversial conclusions. Now is a time to consider optimal patient selection and therapeutic strategy using MitraClip system.

Peri-procedural elevated B-type natriuretic peptide (BNP) is also associated with worse outcomes following transcatheter aortic valve implantation (TAVI). However, the mechanism of BNP regulation in patients with severe aortic stenosis (AS) remains unknown. Consecutive patients with severe AS who were referred for TAVI were enrolled in our prospective registry. BNP levels were correlated with other clinical variables. Ninety-six patients (84.7 ± 5.0 years old, 34% males) were investigated in this study. Plasma BNP averaged 353 ± 179 pg/mL. Log10 BNP had no significant correlation with severity of AS including aortic valve area and maximum flow velocity across the aortic valve (P > 0.05 for all), whereas a higher left ventricular end-diastolic dimension (LVDd) index was a significant factor associating with BNP >100 pg/mL with an odds ratio of 1.34 (95% confidence interval 1.06-1.52, P = 0.004) adjusted for several other echocardiographic parameters, with a cutoff of 30.8 mm/m2 (equivalent to LVDd 44 mm). In conclusion, among the patients with severe AS who undergo TAVI, even slight eccentric hypertrophy can cause a considerable increase in BNP level.

Background: Transthyretin amyloid cardiomyopathy is a progressive disease with a poor prognosis. There had been no specific treatment for transthyretin amyloid cardiomyopathy until tafamidis received expanded approval in March 2019 in Japan. However, the clinical efficacy of tafamidis remains unknown. Methods and Results: We initiated tafamidis treatment in 9 patients (median age 78 years; 89% male) from May 2019 to April 2020. Within 6 months after initiation, 1 patient discontinued prematurely and 2 patients were hospitalized due to worsening heart failure, with 1 of these patients discontinuing therapy. There were no significant changes in plasma B-type natriuretic peptide and serum troponin I concentrations over the 6-month treatment period, but interventricular septum thickness increased in 3 of 6 patients. Conclusions: Further evaluation of tafamidis therapy in a larger patient cohort with transthyretin amyloid cardiomyopathy is warranted to determine the optimal therapeutic strategy.

BACKGROUND Abnormal atrial potential (AAP) during sinus rhythm may be a critical ablation target for atrial fibrillation. However, the assessment of local electrograms throughout the left atrium is difficult. Thus, we sought to investigate the effectiveness of Ripple map guided AAP ablation. METHODS AND RESULTS AAP areas were determined by Ripple mapping on the CARTO system in 35 patients (Ripple group) by marking the area where small deflections persisted after the first deflection wavefront had passed. Following pulmonary vein isolation, AAP areas were ablated. If AAP areas were located on the left atrial posterior wall, the posterior wall was isolated. The outcome of this approach was compared with that of 66 patients who underwent an empirical linear ablation approach (control group). There were no differences in patient characteristics between the groups. The total radiofrequency application time and procedure time were shorter in the Ripple group than in the control group (radiofrequency application time, 48 ± 14 minutes vs 61 ± 13 minutes, P

Background: Post hoc analysis was used to investigate the effects of renal function on the efficacy and safety of landiolol using data from the J-Land II study, which evaluated landiolol in patients with hemodynamically unstable ventricular tachycardia (VT) or ventricular fibrillation (VF) who were refractory to Class III antiarrhythmic drugs. Methods and Results: Patient data from the J-Land II study (n=29) were stratified by renal function (estimated glomerular filtration rate [eGFR]

An intra-aortic balloon pump (IABP) is a device of internal counterpulsation. Inflation of the balloon in diastole results in a potential increase in coronary blood flow and an improvement in systemic perfusion, and deflation at the end of diastole reduces left ventricular afterload, although the hemodynamic effects are relatively small. With its favorable safety profile due to fewer adverse events, IABP has been used for more than 5 decades as the most common mechanical circulatory support device for cardiogenic shock. Recently, however, other short-term devices have become available, and the position of IABP for cardiogenic shock is rapidly changing. Meanwhile, novel improvements in knowledge and technology are pushing the boundaries of this device. In this review, we summarize the basic physiology and current evidence of this device and then discuss the outlook and implications of IABP in the future.

Despite optimal management, we sometimes experience refractory hemolysis requiring extensive device speed reduction or continuous hemodiafiltration following Impella implantation. However, pre-procedural predictors of such a refractory hemolysis remain unknown. In this study, we investigated the pre-procedural factors, including the echocardiographic narrow angle between aortic and mitral annulus, associating with the occurrence of refractory hemolysis following Impella insertion. We enrolled 26 patients (71 years, 65% male) who received Impella insertion between March 2018 and November 2019. Among baseline characteristics, the angle between aortic and mitral annulus

The reduction of pulmonary congestion is an essential clinical target in the management of chronic heart failure. This proves to be challenging given the lack of a gold standard method to quantify the degree of pulmonary congestion both quickly and non-invasively. Remote dielectric sensing (ReDS) is a non-invasive electromagnetic energy-based technology to quantify lung fluid levels as a percentage within minutes. This technique, due to its high negative predictive value, may be a useful tool particularly to rule out primarily cardiac causes of dyspnea in ambulatory patients when the values are normal. Further studies are warranted to establish ReDS-guided management of congestive heart failure patients.

Sacubitril/valsartan has demonstrated its prognostic advantageousness over enalapril in patients with heart failure with a reduced ejection fraction. However, the optimal therapeutic strategy using sacubitril/valsartan in real-world practice, particularly among a Japanee cohort, remains uncertain. A 75-year-old man with systolic heart failure and chronic kidney disease was administered sacubitril/valsartan. Plasma B-type natriuretic peptide transiently increased, accompanied by an increase in the urine volume, which allowed us to terminate loop diuretics. The estimated glomerular filtration rate as well as heart failure symptom improved at the one-month follow-up. Sacubitril/valsartan might be a promising option to preserve the renal function and improve clinical outcomes when the dose of concomitant diuretics can be decreased, although further large-scale studies are warranted to validate our hypothesis.

Sacubitril/valsartan improves mortality and morbidity in patients with heart failure with reduced ejection fraction. However, its impact on right heart failure remains unknown. We experienced a 70-year-old man who was started on sacubitril/valsartan to treat his right heart failure with moderate tricuspid regurgitation. Following the 3-month sacubitril/valsartan treatment, a functional and geological improvement was observed in the right heart as well as amelioration of his congestive symptoms. Sacubitril/valsartan might improve right heart failure in addition to conventionally-proven left heart failure. Further large-scale studies are warranted to validate our findings.