Short-term impact of kampo goreisan in patients with congestive heart failure refractory to tolvaptan-incorporated medical therapy.

We often encounter patients with congestive heart failure refractory to conventional diuretics therapy. Kampo goreisan (Tsumura &Co. Tokyo, Japan) is receiving great concern in mediating body water balance, particularly for such a cohort. However, its detailed biological mechanism remains uncertain. Patients who received goreisan to treat congestive heart failure refractory to tolvaptan-incorporated medical therapy were prospectively included and observed for one week during the therapeutic period. The change in urine biomarkers during the first 24 h was assessed as a primary concern. Baseline factors associated with an increase in urine volume during the first 24 h were investigated as a secondary concern. A total of 18 patients were included. Median age was 81 (77, 86) and 12 (67%) were men. During the first 24 h after the initiation of goreisan, urine cyclic AMP tended to decrease, urine aquaporin-2 decreased significantly, urine osmolality decreased significantly, and urine volume tended to increase. Baseline higher common logarithm of plasma B-type natriuretic peptide was associated with any increases in urine volume during the first 24 h with an odds ratio of 73.2 (95% confidence interval 1.04-5149, p = 0.048). Baseline plasma B-type natriuretic peptide level had a positive correlation with a change in urine volume between baseline and day 1 (r = 0.533, p = 0.026). Goreisan may increase urine volume even in patients with congestive heart failure refractory to tolvaptan-incorporated medical therapy by modulating aquaporin-2 systems in the collecting duct, particularly in individuals with advanced heart failure accompanying significant congestion. Goreisan may have a regulatory effect on body fluid, rather than just forcing aquaresis.

A case of destination therapy for post-fulminant myocarditis with myelodysplastic syndrome.

We encountered a 64-year-old woman who experienced fulminant myocarditis and underwent treatment with veno-arterial extracorporeal membrane oxygenation and Impella CP support. Subsequently, she underwent a device upgrade to Impella 5.5 and received continuous hemodiafiltration for 3 months. During mechanical circulatory support, she developed refractory anemia and thrombocytopenia, leading to a diagnosis of myelodysplastic syndrome. Following the removal of the devices, she no longer required blood transfusions. She received HeartMate 3 left ventricular assist device implantation as a destination therapy indication despite the presence of myelodysplastic syndrome. She was successfully managed by aspirin-free antithrombotic therapy without any hemocompatibility-related adverse events for 4 months after index discharge on foot. We present a patient with a unique and rare presentation, wherein HeartMate 3 was implanted and successfully managed without aspirin to prevent bleeding complications associated with myelodysplastic syndrome.

Successful management of HeartMate 3 in a patient with arrhythmogenic right ventricular cardiomyopathy.

The management of right heart failure during durable left ventricular assist device (LVAD) support remains an unsolved issue so far. We had a 44-year-old male patient who was diagnosed with arrhythmogenic right ventricular cardiomyopathy and received HeartMate 3 LVAD (Abbott, USA) implantation as a bridge-to-transplant indication. The pump speed was adjusted as low as 4500 rpm to avoid the left ventricular narrowing and interventricular septal leftward shift. Riociguat was administered to decrease the afterload of the right ventricle and increase the preload of the left ventricle, in addition to the combination of neurohormonal blockers. Frequent low-flow alarm events eventually disappeared after amlodipine administration, and he was successfully returned to work. We here present a unique management in a patient with right heart failure due to arrhythmogenic right ventricular cardiomyopathy during HeartMate 3 LVAD support.

Impact of Pemafibrate Therapy on Reducing Small Dense Low-Density-Lipoprotein-Cholesterol Levels in Patients with Hypertriglyceridemia.

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

Constipation as a Drug-Related Adverse Effect in Patients with Hyperkalemia: Sodium Zirconium Cyclosilicate versus Conventional Potassium Binders.

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

Clinical Implication of Supra-Normal Left Ventricular Ejection Fraction in Patients Undergoing Transcatheter Aortic Valve Replacement.

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

Pulmonary Artery Pulsatility Index and Hemolysis during Impella-Incorporated Mechanical Circulatory Support.

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 (<1.3) significantly correlated with the occurrence of hemolysis with an odds ratio of 11.65 (95% confidence interval 1.58−85.98, p = 0.017), adjusted for other potential confounders. Survival discharge was significantly lower in patients with lower PAPi (<1.3) (50% vs. 86%, p = 0.019). Conclusions: The results of this study suggest that patients with right ventricular impairment indicated by lower PAPi following the initiation of Impella-incorporated mechanical circulatory support have a higher risk of hemolysis.

A case of chronic myocarditis remitted by immunosuppressive and central extracorporeal membrane oxygenation therapy.

The concept and therapeutic strategy for chronic lymphocytic myocarditis remain unestablished. We had a 57-year-old man with advanced biventricular (predominantly right ventricular) failure due to chronic lymphocytic myocarditis. He received central extracorporeal membrane oxygenation therapy that was explanted on day 129 following the aggressive steroid pulse and plasma exchange therapy. Infiltration of inflammatory cells persisted even after the device removal, which required long-term oral steroid administration after the index discharge on day 200. High-sensitivity cardiac troponin T level was normalized and inflammatory cell infiltration was remitted following post-discharge 4-month 10 mg/day prednisolone therapy. Aggressive immunosuppressive therapy under mechanical circulatory support might be a promising strategy for those with chronic lymphocytic myocarditis. .

Percutaneous transseptal transcatheter mitral valve-in-valve replacement for degenerated mitral bioprosthesis: The first experience in Japan.

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. .

Efficacy of 50 mg pregabalin for prevention of postoperative neuropathic pain after video-assisted thoracoscopic surgery and thoracotomy: a 3-month prospective randomized controlled trial.

BACKGROUND: This study analyzed the preventive effect of 50 mg/day pregabalin on postoperative neuropathic pain, and any additional benefits related to sleep and respiratory function. METHODS: This prospective randomized controlled study included lung resection patients 20-89 years of age. Patients were randomly assigned to the treatment (pregabalin; initial dose, 50 mg/day) or control (non-steroidal anti-inflammatory drugs) group. Pregabalin patients received non-steroidal anti-inflammatory drugs and pregabalin (25 mg, twice daily) from the second postoperative day. Pain scores, neuropathic pain, analgesic use, respiratory function, and insomnia scale scores for 3 months after surgery were evaluated. RESULTS: This study included 46 patients who received pregabalin and 46 control patients. Pregabalin patients had significantly less postoperative neuropathic pain than control patients (19.6% vs. 41.3%; P=0.0404), and their duration of neuropathic pain was significantly shorter (30 vs. 90 days; P=0.024). The onset of postoperative neuropathic pain, insomnia scale scores, and respiratory function were similar between groups. No pregabalin-related adverse events were reported. CONCLUSIONS: Pregabalin (50 mg/day) had a significant preventive effect on postoperative neuropathic pain after thoracic surgery, without side effects. Early postoperative administration of pregabalin would help prevent neuropathic pain and provide better pain control after thoracic surgery.