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.

The no-flow phenomenon following drug-coated balloon angioplasty in a patient with chronic limb-threatening ischemia and a history of below-knee amputation.

The endovascular treatment using a drug-coated balloon (DCB) reduces restenosis and target vessel re-vascularization rate in patients with peripheral artery disease such as claudication and chronic limb-threatening ischemia (CLTI). However, its safety and efficacy in patients with post-below-knee amputation remain unknown. We had a patient with CLTI and a history of below-knee amputation, who suffered a no-flow phenomenon following DCB angioplasty that required above-knee amputation. DCB angioplasty might not be appropriate for those with severe CLTI and histories of amputation. Learning objective: The present report describes the risk of endovascular treatment using a drug-coated balloon for chronic limb-threatening ischemia patients with a below-knee amputated limb.

Spatially resolved measurement of helium atom emission line spectrum in scrape-off layer of Heliotron J by near-infrared Stokes spectropolarimetry.

For plasma spectroscopy, Stokes spectropolarimetry is used as a method to spatially invert the viewing-chord-integrated spectrum on the basis of the correspondence between the given magnetic field profile along the viewing chord and the Zeeman effect appearing on the spectrum. Its application to fusion-related toroidal plasmas is, however, limited owing to the low spatial resolution as a result of the difficulty in distinguishing between the Zeeman and Doppler effects. To resolve this issue, we increased the relative magnitude of the Zeeman effect by observing a near-infrared emission line on the basis of the greater wavelength dependence of the Zeeman effect than of the Doppler effect. By utilizing the increased Zeeman effect, we are able to invert the measured spectrum with a high spatial resolution by Monte Carlo particle transport simulation and by reproducing the measured spectra with the semiempirical adjustment of the recycling condition at the first walls. The inversion result revealed that when the momentum exchange collisions of atoms are negligible, the velocity distribution of core-fueling atoms is mainly determined by the initial distribution at the time of recycling. The inversion result was compared with that obtained using a two-point emission model used in previous studies. The latter approximately reflects the parameters of atoms near the emissivity peak.

Chronotype of Lung Fluid Levels in Patients with Chronic Heart Failure.

BACKGROUND: The variation in lung fluid levels dependent on chronotype in patients with chronic heart failure is unclear. Remote dielectric sensing (ReDSTM) is a novel non-invasive system to quantify the lung fluids, which may correlate to intracardiac filling pressures. We aimed to understand the variation in ReDS measurements by chronotype in patients with chronic heart failure. METHODS: The patients who were hospitalized for heart failure exacerbations between November 2021 and March 2022 were prospectively included. ReDS values were measured at clinically stable conditions at the following three time points during the day: 5:00 (morning), 12:00 (noon), and 21:00 (night) (manufacture-recommended reference of ReDS value: between 25% and 35%). RESULTS: Twelve patients were included. The median age was 84 (75, 90) years and four patients (33%) were men. The median plasma B-type natriuretic peptide was 235 (178, 450) pg/mL. The median ReDS value was 38% (23%, 41%) in the morning. The ReDS value decreased significantly at the noon measurement, down to 28% (23%, 29%) (p = 0.005) and again increased significantly at the night measurement, up to 31% (27%, 42%) (p = 0.002). The patients were clinically stabilized during the observational period. CONCLUSIONS: the lung fluid level varied considerably in patients with chronic heart failure following clinical stabilization.

Association between Lung Fluid Levels Estimated by Remote Dielectric Sensing Values and Invasive Hemodynamic Measurements.

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.

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.

Cardio-Ankle Vascular Index and Heart Failure Hospitalization in Patients With Aortic Stenosis Following Transcatheter Aortic Valve Implantation.

Background: The cardio-ankle vascular index (CAVI) is associated with the severity of vascular stiffness and heart failure (HF). However, little is known about CAVI in aortic stenosis (AS) patients, probably because of the difficulty of accurately measuring CAVI in these patients owing to their slow-rising pulse. In this study, we investigated the prevalence and prognostic impact of abnormally elevated CAVI measured after transcatheter aortic valve implantation (TAVI). Methods and Results: Among patients with AS who underwent TAVI, those with bilateral peripheral artery disease, atrial fibrillation, and systolic HF were excluded. The effect of post-TAVI elevated CAVI (defined as ≥9.0) on HF readmission after the index discharge was investigated. In all, 149 patients (mean [±SD] age 84.8±5.6 years, 24.2% men, mean [±SD] post-TAVI CAVI 9.6±1.4) were included in the study. There was no significant difference in baseline characteristics between groups with and without elevated CAVI, except for lower high-density lipoprotein cholesterol (HDL-C) and a higher prevalence of HF history in the group with elevated CAVI (P<0.05 for both). Post-TAVI elevated CAVI (n=102) was associated with lower freedom from HF recurrence during the observational period (89.1% vs. 100%; median 726 days [interquartile range 329-1,104 days]; P<0.05). Moreover, CAVI was an independent predictor of HF occurrence (hazard ratio 1.62; 95% confidence interval 1.07-2.46; P=0.022). Conclusions: Elevated CAVI was associated with HF occurrence before and after TAVI.

Validation of Inter-Rater and Intra-Rater Reliability of Remote Dielectric Sensing Measurement.

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 (P < 0.001). For the inter-rater reliability, ICC (2, 1) and ICC (2, 3) were 0.683 and 0.866, respectively (P < 0.001). 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.

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.

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.

Impact of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Renal Function in Patient with Heart Failure.

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

Acute Heart Failure in a Patient with Occult Barlow's Disease Receiving Bevacizumab.

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.

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.

How to Estimate the Optimal Heart Rate in Patients with Heart Failure with Preserved Ejection Fraction.

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.

Identification of Anemia for Predicting Mid-Term Prognosis After Transcatheter Aortic Valve Implantation in Japanese Patients　- Insights From the OCEAN-TAVI Registry.

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 <10.9 g/dL for men and <10.4 g/dL for women. The presence of anemia, uniquely defined for the Japanese cohort, was independently associated with 2-year mortality following TAVI, with an odds ratio of 1.77 (95% confidence interval 1.39-2.25) adjusted for 14 other clinical variables. Conclusions: The existence of anemia, uniquely defined for the Japanese cohort, was associated with mid-term mortality following TAVI.

Impact of optimal heart rate on left ventricular reverse remodeling and functional improvement in patients with systolic heart failure.

Heart rate modulation therapy using ivabradine reduces mortality and morbidity in patients with systolic heart failure, whereas too reduced heart rate seems to worsen the clinical outcome. The optimal heart rate during heart rate modulation therapy remains unknown. Consecutive patients with left ventricular ejection fraction < 50% who received echocardiographic assessments and simultaneous heart rate measurements were retrospectively investigated. Theoretically ideal heart rate was calculated using a previously proposed formula: 93 - 0.13 × (deceleration time [msec]). Impacts of heart rate on the 1-year echocardiographic left ventricular reverse remodeling were compared among the three groups stratified by the heart rate status: optimal heart rate group (within 10 bpm of ideal heart rate), below-optimal heart rate group (< 10 bpm of ideal heart rate), and above-optimal heart rate group (> 10 bpm of ideal heart rate). A total of 75 patients (70 years old, 60 men) were included. There were no significant differences in the baseline characteristics among the three groups, except for the higher prevalence of tolvaptan use and higher plasma B-type natriuretic peptide level in the below-optimal heart rate group. Left ventricular end-diastolic diameter (from 55 to 54) and left ventricular ejection fraction (from 39 to 46) improved significantly only in the optimal heart rate group at 1-year follow-up (p < 0.05 for both). Optimal heart rate, which was calculated using a formula consisting of deceleration time, was associated with cardiac reverse remodeling in patients with systolic heart failure. Prospective study to investigate the implication of deceleration time-guided aggressive heart rate optimization is the next concern.

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. .

Validation of Noninvasive Remote Dielectric Sensing System to Quantify Lung Fluid Levels.

BACKGROUND: The accuracy of the remote dielectric sensing (ReDSTM) system, which is a noninvasive electromagnetic-based technology to quantify lung fluid levels, particularly among those with small body size, remains uncertain. METHODS: Hospitalized patients with and without heart failure underwent assessment of lung fluid levels with ReDS and successive chest computed tomography imaging. We performed a correlation analysis of the ReDS measurement, representing lung fluid levels, and computed tomography-derived high attenuation area percentage, which also provides a spatial quantification of lung fluid level. RESULTS: A total of 46 patients (median 76 years old, 28 men), including 28 patients with heart failure, were included. The median ReDS value was 28% (interquartile: 23%, 33%), and the median percentage of high attenuation area was 21.6% (14.4%, 28.5%). ReDS values and percentage of high attenuation area were moderately correlated (r = 0.65, p < 0.001), irrespective of the existence of heart failure. ReDS value independently predicted the percentage of high attenuation area seen on computed tomography (p < 0.001). CONCLUSIONS: The ReDS system may be a promising, noninvasive tool to quantify fluid lung levels, as validated by comparison with chest computed tomography imaging. Further studies are warranted to validate the utility and applicability of this technology to a variety of clinical scenarios.

Impact of the angle between aortic and mitral annulus on the occurrence of hemolysis during Impella support.

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, < 126.5°, was an independent risk factor of refractory hemolysis with an adjusted hazard ratio of 7.840 (95% confidence interval 0.925-66.44) and was associated with lower 30-day survival (64% vs. 100%, p = 0.0116). The narrow angle between aortic and mitral annulus might be a useful tool to risk-stratify the occurrence of refractory hemolysis following Impella insertion.

The impact of changes in B-type natriuretic peptide levels on prognosis after transcatheter aortic valve implantation.

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 < 0.001). There were 48 patients (68.6%) in the responder group and 22 patients (31.4%) in the non-responder group. Kaplan-Meier estimates showed that the responder group had lower all-cause death and hospitalization for HF than the non-responder group by a log rank test (all-cause mortality; p = 0.006, hospitalization rate for HF; p < 0.001). The predictor of the non-responder group using multivariate logistic regression analysis was AF (OR 4.2, 95% CI 1.15-16.2, p = 0.03). A reduction of BNP was associated with improved prognosis after TAVI.