Paradoxical prognostic impact of severe aortic stenosis following trans-catheter aortic valve implantation.

BACKGROUND: Aortic valve replacement is recommended for patients with "very severe" aortic stenosis (AS), irrespective of symptomatic manifestation. Nonetheless, the prognostic ramifications of "very severe" AS, as opposed to "severe" AS, subsequent to trans-catheter aortic valve implantation (TAVI) remain enigmatic. METHODS: We enrolled consecutive patients who received TAVI at our institute between May 2015 and April 2021. We scrutinized the impact of baseline "very severe" AS upon 3-year all-cause death or heart failure hospitalization following TAVI, in comparison to "severe" AS. RESULTS: A total of 239 patients (84.8 ±â€¯5.4 years old, 58 men) were included. Baseline "very severe" AS was observed in 65 (27 %) patients, who exhibited more advanced hypertrophy and higher B-type natriuretic peptide levels compared to those with "severe" AS (p < 0.05 for both). Baseline "very severe" AS was paradoxically associated with higher freedom from the primary endpoint following TAVI compared to those with "severe" AS (p = 0.01). CONCLUSIONS: The presence of baseline "very severe" AS was paradoxically associated with improved clinical outcomes subsequent to TAVI, in contrast to the cases of "severe" AS.

A Case of Liver Cancer with Overlapping Myasthenia Gravis, Myocarditis, Seronegative Autoimmune Autonomic Ganglionopathy, and Myositis Symptoms Induced by Atezolizumab: A Case Report.

An 83-year-old man with hepatocellular carcinoma developed muscle weakness, ptosis, and dyspnea 3 weeks after receiving atezolizumab. Soon after, mechanical ventilation was initiated, which was followed by marked blood pressure spikes. The levels of creatine kinase and troponin-I were significantly elevated, and acetylcholine receptor antibodies were positive. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced myositis, myasthenia gravis (MG), myocarditis, and suspected autoimmune autonomic ganglionopathy (AAG). After immunotherapy, the serum markers and blood pressure normalized, and he was weaned from the ventilator after five months. To our knowledge, this is the first reported case of AAG secondary to ICI-induced myositis, MG, and myocarditis.

Prognostic impact of elevated erythropoietin levels in patients with severe aortic stenosis receiving trans-catheter aortic valve implantation.

BACKGROUND: Elevated endogenous erythropoietin (EPO) levels are associated with worse clinical outcomes in patients with heart failure (HF). The clinical implication of endogenous EPO levels in patients undergoing trans-catheter aortic valve implantation (TAVI) beyond other conventional risk factors remains unknown. METHODS: Consecutive patients with EPO measurements who underwent TAVI for the treatment of their severe aortic stenosis at our institute between May 2015 and December 2020 were included. The association between the endogenous EPO levels and the primary outcome consisting of all-cause mortality and HF hospitalization was evaluated. RESULTS: A total of 263 patients (85.1 ±â€¯5.1 years old, 74 men) were included and tertiled according to the baseline EPO levels. The high EPO group had more advanced anemia, renal impairment, and hypoalbuminemia than the other two tertiled groups (p < 0.05 for both). Patients with high EPO had a significantly higher cumulative incidence of the primary outcomes compared to the other two groups (p = 0.002) with an adjusted hazard ratio of 6.0 (95 % confidence interval 1.9-18.1) in its logarithmic value (p < 0.001). CONCLUSIONS: Elevated baseline EPO levels were independently associated with mortality and morbidity following TAVI. The clinical implication of aggressive intervention on the elevated EPO levels in this cohort remains the next concern.

Novel Ramp Test to Optimize Pressure Setting of Adaptive Servo-Ventilation Using Non-Invasive Lung Fluid Level Quantification.

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.

A Rescue Use of ECPELLA for Sepsis-Induced Cardiogenic Shock Followed by Mitral Valve Replacement.

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

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. .

A novel therapeutic strategy: remote dielectric sensing-guided management of pulmonary congestion.

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. .

Prognostic implication of pulmonary artery pulsatility index before transcatheter aortic valve replacement.

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.

Typing of the Gut Microbiota Community in Japanese Subjects.

Gut microbiota are involved in both host health and disease and can be stratified based on bacteriological composition. However, gut microbiota clustering data are limited for Asians. In this study, fecal microbiota of 1803 Japanese subjects, including 283 healthy individuals, were analyzed by 16S rRNA sequencing and clustered using two models. The association of various diseases with each community type was also assessed. Five and fifteen communities were identified using partitioning around medoids (PAM) and the Dirichlet multinominal mixtures model, respectively. Bacteria exhibiting characteristically high abundance among the PAM-identified types were of the family Ruminococcaceae (Type A) and genera Bacteroides, Blautia, and Faecalibacterium (Type B); Bacteroides, Fusobacterium, and Proteus (Type C); and Bifidobacterium (Type D), and Prevotella (Type E). The most noteworthy community found in the Japanese subjects was the Bifidobacterium-rich community. The odds ratio based on type E, which had the largest population of healthy subjects, revealed that other types (especially types A, C, and D) were highly associated with various diseases, including inflammatory bowel disease, functional gastrointestinal disorder, and lifestyle-related diseases. Gut microbiota community typing reproducibly identified organisms that may represent enterotypes peculiar to Japanese individuals and that are partly different from those of indivuals from Western countries.

Successful Management of Pheochromocytoma Crisis with Cardiogenic Shock by Percutaneous Left Ventricular Assist Device.

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

Trans-Apical Transcatheter Aortic Valve Replacement in a Dialysis Patient with Systolic Heart Failure.

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

Relationship Between Body Posture and Lung Fluid Volume Assessed Using a Novel Noninvasive Remote Dielectric Sensing System.

Background: The relationship between body posture and lung fluid level has not been quantified thus far. Remote dielectric sensing (ReDSTM) is a recently introduced non-invasive electromagnetic-based technology to quantify lung fluid percentage. Methods and Results: ReDS values were measured at different body postures (i.e., sitting, supine, and supine with legs elevated) in a healthy volunteer cohort (n=16; median age 39 years, 69% men, median [interquartile range {IQR}] body mass index 23.3 kg/m2 [21.0-26.2 kg/m2]). In the sitting position, the median ReDS value was 27% (IQR 25-29%). The ReDS value increased significantly in the supine position (median 28%; IQR 27-30%; P=0.009), and increased further upon leg elevation (median 29%; IQR 28-32%; P=0.001). Conclusions: In this proof-of-concept study, the relationship between body posture and lung fluid level was quantitatively validated in a healthy cohort.

Clinical Implications of Changes in Respiratory Instability Following Transcatheter Aortic Valve Replacement.

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 (<33 s, 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.

Clinical implications of troponin-T elevations following TAVR: Troponin Increase Following TAVR.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Post-procedural increase in serum troponin-T level was associated with adverse clinical outcomes following TAVR.

Clinical Implications of Sodium Zirconium Cyclosilicate Therapy in Patients with Systolic Heart Failure and Hyperkalemia.

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 <50% and hyperkalemia who had completed 3-month SZC therapy were retrospectively included. Serum potassium levels, the dose of renin-angiotensin-aldosterone system inhibitors, and echocardiographic parameters during the 3-month SZC therapy as compared with the pretreatment 3-month period were investigated. A total of 24 patients (median 77 years old, 71% men, median left ventricular ejection fraction 41%) received a 3-month SZC therapy without any associated adverse events including hypokalemia. Compared with the pretreatment period, serum potassium levels decreased, doses of renin-angiotensin-aldosterone system inhibitors increased, and the left ventricular ejection fraction and plasma B-type natriuretic peptide levels improved following the 3-month SZC therapy (p < 0.05 for all). CONCLUSIONS: SZC may be a promising therapeutic option to improve hyperkalemia, indirectly allowing up-titration of renin-angiotensin-aldosterone system inhibitors and facilitating reverse remodeling in patients with heart failure with a left ventricular ejection fraction <50% and hyperkalemia.

Implication of Mineralocorticoid Receptor Antagonist Esaxerenone in Patients With Heart Failure With Preserved Ejection Fraction.

Background: The implications of mineralocorticoid receptor antagonists, including the newly introduced esaxerenone, on cardiac reverse remodeling in patients with heart failure with preserved ejection fraction (HFpEF) remain uncertain. Methods and Results: We included patients with HFpEF who received esaxerenone for hypertension between November 2019 and July 2021 in this retrospective study. Changes in left ventricular mass index (LVMI) were compared between the 6-month pretreatment period (without esaxerenone) and the 6-month treatment period (on esaxerenone). Thirty-three patients (median age 74 years [interquartile range {IQR} 70-81 years]; 33% male, median systolic blood pressure [SBP] 135 mmHg [IQR 123-148 mmHg]) were included in the study and completed 6-month esaxerenone therapy without any adverse events. During the pretreatment period, SBP decreased significantly (P=0.009), whereas LVMI remained unchanged (P=0.30). During the esaxerenone treatment period, both SBP and LVMI decreased significantly (P=0.003 and P=0.001, respectively). Conclusions: Esaxerenone may have beneficial effects of reverse remodeling in patients with HFpEF when used to treat hypertension. Further studies are needed to understand which patient populations may see greater benefits with esaxerenone.

Combination Therapy Using Sodium Zirconium Cyclosilicate and a Mineralocorticoid Receptor Antagonist in Patients with Heart Failure and Hyperkalemia.

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.

Management of hyperkalemia in chronic heart failure using sodium zirconium cyclosilicate.

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 <4.0 mEq/L. Baseline lower serum potassium level was associated with the post-SZC hypokalemia. CONCLUSIONS: SZC immediately decreases approximately 1.0 mEq/L of serum potassium in patients with heart failure and hyperkalemia. However, caution should be exercised when utilizing SZC at a loading dose specifically in those with mild hyperkalemia to prevent iatrogenic hypokalemia.

Renoprotective Effect of the Mineralocorticoid Receptor Antagonist Esaxerenone.

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.

The death of patients with terminal cancer: the distress experienced by their children and medical professionals who provide the children with support care.

BACKGROUND: Few studies have been conducted on the experiences of children of terminally ill patients or hospital-based medical professionals supporting such children. AIM: This study explored distress among individuals whose parents died of cancer in childhood and among hospital-based medical professionals supporting such children. DESIGN: A qualitative study. SETTING/PARTICIPANTS: The sample was 12 adults whose parents had died of cancer in childhood and 20 hospital-based medical professionals supporting children of patients' with terminal cancer. In-depth interviews were conducted, focusing on the distress experienced by the participants. The data were analysed thematically. RESULTS: Among adults whose parents died of cancer in childhood, we identified themes related to the period before death (eg, concealing the parent's illness), the time of death (eg, alienation due to isolation from the parent), soon after death (eg, fear and shock evoked by the bizarre circumstances, regrets regarding the relationship with the deceased parent before death), several years thereafter (ie, distinctive reflection during adolescence, prompted by the parent's absence) and the present time (ie, unresolved feelings regarding losing the parent). We identified seven themes among the medical professionals (eg, lack of knowledge/experience with children, the family's attempts to shield the child from the reality of death, estrangement from the family once they leave the hospital). CONCLUSIONS: An important finding of the study is that the participants' grief reaction to their parents' deaths during childhood was prolonged. Moreover, hospital medical professionals may find it difficult to directly support affected children. Comprehensive support involving organisations (eg, local communities) may be necessary for children who have lost a parent.