Overview of the 87th Annual Scientific Meeting of the Japanese Circulation Society (JCS2023)　- New Challenge With Next Generation.

The 87thAnnual Meeting of the Japanese Circulation Society (JCS2023) was held in March 2023 in Fukuoka, Japan, marking the first in-person gathering after the COVID-19 pandemic. With the theme of "New Challenge With Next Generation" the conference emphasized the development of future cardiovascular leaders and technologies such as artificial intelligence (AI). Notable sessions included the Mikamo Lecture on heart failure and the Mashimo Lecture on AI in medicine. Various hands-on sessions and participatory events were well received, promoting learning and networking. Post-event surveys showed high satisfaction among participants, with positive feedback on face-to-face interactions and the overall experience. JCS2023, attended by 17,852 participants, concluded successfully, marking a significant milestone in post-pandemic meetings, and advancing cardiovascular medicine.

"Kyushu-style" collaboration between the implantable ventricular assist device implantation and management centers: a republication of the article published in Japanese journal of artificial organs.

Collaboration between the implantation centers, management centers, and regional core hospitals is a key factor in securing long-term implantable ventricular assist device (VAD) management. In Kyushu, a management system for patients with implantable VADs has been established at the prefectural and regional levels. Presently, six implantable VAD implantation centers and seven management centers exists in the eight prefectures of Kyushu and Okinawa, with at least one specialized VAD centers in each prefecture. This collaborative management system allows patients with VADs to receive seamless treatment based on the same management concept wherever they live. In fact, approximately half of the present outpatients treated at our center reside outside the prefecture and are managed in collaboration with management centers and regional core hospitals. Among our patients, there were no significant differences in survival or rehospitalization-free rates between patients with VADs in and out of the prefecture, suggesting that the place of residence did not affect the outcome. With the increase in the number of patients with VADs and the diversification of patients, patient management has become more complex. Mutual collaboration between the implantation centers, management centers, and regional core hospitals, is essential to improve the quality of VAD management. This review was created based on a translation of the Japanese review written in the Japanese Journal of Artificial Organs in 2023 (Vol. 52, No. 1, pp. 85-88), with some modifications.

Postoperative tolvaptan use in left ventricular assist device patients: The TOLVAD randomized pilot study.

PURPOSE: Tolvaptan, a selective vasopressin type-2 antagonist, has been shown to increase serum sodium (Na) and urine output in hyponatremic left ventricular assist device (LVAD) patients in retrospective studies. In this prospective randomized pilot study, we aimed to assess the efficacy of tolvaptan in this population. METHODS: We conducted a prospective, randomized, non-blinded pilot study of LVAD recipients with post-operative hyponatremia (Na < 135 mEq/L) (NCT05408104). Eligible participants were randomized to receive tolvaptan 15 mg daily in addition to usual care versus usual care alone. The primary outcome was a change in Na level and estimated glomerular filtration rate (eGFR), from the first post-operative day of hyponatremia (the day of randomization) to discharge. RESULTS: A total of 33 participants were enrolled, and 28 underwent randomization (median age 55 [IQR 50-62]), 21% women, 54% Black, 32% ischemic cardiomyopathy, median baseline Na 135 (IQR 134-138). Fifteen participants were randomized to tolvaptan (TLV) and 13 were randomized to usual care alone (No-TLV). Mean change in Na from randomization to discharge in the TLV group was 2.7 mEq/L (95%CI 0.7-4.7, p = 0.013) and 1.8 (95%CI 0.5-4.0, p = 0.11) in the No-TLV group, though baseline and final Na levels were similar between groups. The mean change in eGFR was 2.6 ml/min/1.73 m2 (95%CI 10.1-15.3, p = 0.59) in TLV versus 7.5 ml/min/1.73 m2 (95%CI 5.2-20.2, p = 0.15) in No-TLV. TLV participants had significantly more urine output than No-TLV patients during their first 24 h after randomization (3294 vs 2155 ml, p = 0.043). CONCLUSION: TLV significantly increases urine output, with nominal improvement in Na level, in hyponatremic post-operative LVAD patients without adversely impacting renal function.

Discordance between immunofluorescence and immunohistochemistry C4d staining and outcomes following heart transplantation.

BACKGROUND: Capillary deposition of C4d is an important marker of antibody-mediated rejection (AMR) following heart transplantation (HT). There are two immunopathologic assay methods for detecting C4d: frozen-tissue immunofluorescence (IF) and paraffin immunohistochemistry (IHC). The clinical significance of discrepancy between the results of IF and IHC has not been understood. METHODS AND RESULTS: We reviewed 2187 biopsies from 142 HT recipients who had biopsies with assessment of both IF and IHC staining. Among them, 103 (73%) patients had negative IF and IHC C4d staining (Negative Group) and 32 (23%) patients had positive IF but negative IHC staining (Discordant Group). At the time of positive biopsy, 6 (19%) Discordant patients had graft dysfunction, compared to 5 (5%) Negative patients (p = .022). Cumulative incidence of cellular rejection at 1 year was comparable (31% vs. 29%, p = .46); however, cumulative incidence of AMR was significantly higher in the Discordant group (21% vs. 4%, p = .004). Overall 1-year survival was comparable (90% vs. 96%, p = .24); however, freedom from heart failure (HF) was significantly lower in the Discordant group (70% vs. 96%, p < .001). CONCLUSION: The Discordant group showed higher rates of graft dysfunction, AMR and HF admission than the Negative group.

Donor-derived cell-free DNA is associated with cardiac allograft vasculopathy.

BACKGROUND: The role of donor-derived cell-free DNA (dd-cfDNA) in screening for cardiac allograft vasculopathy (CAV) is unknown. We hypothesized that dd-cfDNA correlates with CAV, markers of inflammation, and angiogenesis in stable heart transplant (HT) recipients. METHODS: Sixty-five HT recipients ≥2 years post-transplant, without recent rejection, were stratified by high (≥0.12%) versus low levels (<0.12%) of dd-cfDNA. A targeted amplification, next-generation sequencing assay (AlloSure® ; CareDx, Inc.) was used to detect dd-cfDNA. Peripheral blood inflammatory and angiogenesis markers were assessed using a multiplex immunoassay system (Bioplex® ). RESULTS: Of 65 patients, 58 patients had a known CAV status and were included. Thirty had high levels of dd-cfDNA (≥0.12%), and 28 had low levels (<0.12%). CAV was present in 63% of patients with high dd-cfDNA vs. 35% with low dd-cfDNA (p = .047). Donor-specific antibodies were present in 25% of patients with high dd-cfDNA vs. 3.8% in those with low dd-cfDNA (p = .03). There were no differences in rejection episodes, inflammatory, or angiogenesis markers. Importantly, dd-cfDNA levels were not different when stratified by time post-transplant. CONCLUSIONS: Higher dd-cfDNA levels were associated with CAV in stable chronic HT recipients. Further studies are warranted to investigate a possible association between dd-cfDNA levels and CAV severity and whether dd-cfDNA can predict CAV progression.

Impact of worsening of aortic insufficiency during HeartMate 3 LVAD support.

Aortic insufficiency remains a difficult to treat and highly morbid condition even in the era of HeartMate 3 left ventricular assist devices (LVADs). The prognostic nature of the longitudinal progression of aortic insufficiency, however, remains unknown. We prospectively collected data on patients who received HeartMate 3 LVAD implantation, who had assessments of aortic insufficiency using a novel Doppler echocardiography obtained at outflow graft at three (baseline) and 6 months postimplant. Patients with moderate or greater aortic insufficiency at baseline were excluded. The risk of aortic insufficiency progression on 1-year death and readmission for heart failure was investigated. In total, 41 patients (median 51 years old and 29 males) were included. All patients had less than moderate aortic insufficiency at baseline. Of them, 22 patients had worsening aortic insufficiency for 3 months following baseline assessments, which was associated with a significantly higher risk of 1-year death or heart failure readmission rate (41% vs. 11%, P = .023) with a hazard ratio of 3.24 (95% confidence interval 1.02-18.5, P = .038) adjusted for device speed at baseline and destination therapy indication. In patients with HeartMate 3 LVADs, progressive aortic insufficiency may be associated with a higher risk of 1-year death or readmission for heart failure. Close monitoring of patients with baseline aortic insufficiency should be considered as a measure to risk-stratify those for future adverse events.

Undiagnosed Cardiac Sarcoidosis Causing Refractory Heart Failure After Acute Myocardial Infarction due to Thromboembolism.

A 61-year-old woman suffered chest pain and was admitted to a nearby hospital emergency department. She was diagnosed with acute myocardial infarction probably due to thromboembolism in the left anterior descending coronary artery and aspiration thrombectomy was performed. Afterwards, she developed refractory heart failure with severe global left ventricular dysfunction and was transferred to our hospital. An 18F-FDG-PET/CT scan revealed abnormal 18F-FDG uptake in non-infarcted regions of the left ventricle. Non-caseating granulomas were detected by biopsy from a skin eruption. She was diagnosed with cardiac sarcoidosis. In cases of refractory heart failure which cannot be explained only by myocardial infarction, evaluation of other undiagnosed cardiomyopathies is important for optimal management.

HVAD Flow Waveform Estimates Left Ventricular Filling Pressure.

BACKGROUND: HVAD left ventricular assist device flow waveforms provides graphical real-time information linking device performance with invasive hemodynamics. Previous studies have demonstrated a good correlation between the slopes of the ventricular filling phase slope (VFPS) and directly measured pulmonary capillary wedge pressure (PCWP). We aimed to validate the utility of VFPS to estimate PCWP and predict clinical outcomes. METHODS: In this prospective blinded study, screenshots from the HVAD monitor and simultaneous invasive hemodynamic measurements were obtained. Each screenshot was digitized and the VFPS was calculated by 2 independent reviewers who were blinded to the hemodynamic results. The equation PCWP = 7.053 +1.365 × (VFPS) was derived from a previously published dataset and the estimated PCWP was correlated to the actually measured PCWP. RESULTS: One hundred thirty-one sets of simultaneous measurements (VFPS and PCWP) were obtained from 27 HVAD patients (mean age 55 years, 47% male). A previously proposed cutoff of VFPS ≥5.8 L/min/s predicted PCWP ≥ 18 mmHg with 91.5% sensitivity and 95.2% specificity with the area under curve of 0.987. The estimated PCWP significantly correlated with measured PCWP (R2 = 0.65, P < .001) and showed acceptable agreement with measured PCWP. Patients with VFPS ≥ 5.8 L/min/s experienced significantly higher heart failure readmission rates than those without (0.24 vs 0.05 events/y, P < .001). CONCLUSIONS: VFPS of the HVAD flow waveform is a novel noninvasive parameter that can estimate PCWP.

Aortic Insufficiency During HeartMate 3 Left Ventricular Assist Device Support.

BACKGROUND: Aortic insufficiency (AI) is associated with morbidity and mortality in patients with continuous-flow left ventricular assist devices (LVADs), whereas its impact on the HeartMate 3 LVAD cohorts remains uninvestigated. We aimed to investigate the clinical impact of AI on patients with HeartMate 3 LVADs. METHODS AND RESULTS: Consecutive 61 patients (median age 54 years; 67% male) implanted with HeartMate 3 LVAD between 2015 and 2019 were enrolled and underwent echocardiography at 3 months after LVAD implantation. AI severity was quantified by the novel Doppler echocardiographic method obtained at the outflow cannula and the calculated regurgitation fraction of 30% or greater (moderate or greater) was defined as significant. At 3 months after implant, 12 patients (20%) had significant AI. They had a higher incidence of death or heart failure readmissions compared with those without significant AI during a 1-year observational period (70% vs 24%, P = .003) with an adjusted hazard ratio of 2.76 (95% confidence interval 1.03-7.88). CONCLUSIONS: In patients with HeartMate 3 LVAD support, significant AI remains both prevalent and a clinically significant downstream complication.

Longitudinal Trajectories of Hemodynamics Following Left Ventricular Assist Device Implantation.

BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) improve the hemodynamics of patients with advanced heart failure. However, the longitudinal trajectories of hemodynamics in patients after LVAD implantation remain unknown. The aim of this study was to investigate the trends of hemodynamic parameters following LVAD implantation. METHODS AND RESULTS: We retrospectively reviewed patients who underwent LVAD implantation between April 2014 and August 2018. We collected hemodynamic parameters from right heart catheterizations. Of 199 consecutive patients, we enrolled 150 patients who had both pre- and postimplant right heart catheterizations. They had 3 (2, 4) postimplant right heart catheterizations during a follow-up of 2.3 (1.3, 3.1) years. The mean age was 57 ± 13 years, and 102 patients (68%) were male. Following LVAD implantation, pulmonary arterial pressure and pulmonary capillary wedge pressure decreased, and cardiac index increased significantly, then remained unchanged throughout follow-up. Right atrial pressure decreased initially and then gradually increased to preimplant values. The pulmonary artery pulsatility index decreased initially and returned to preimplant values, then progressively decreased over longer follow-up. Subgroup analysis showed significant differences in the trajectories of the pulmonary artery pulsatility index based on gender. CONCLUSIONS: Despite improvement in left-side filling pressures and cardiac index following LVAD implantation, right atrial pressure increased and the pulmonary artery pulsatility index decreased over time, suggesting progressive right ventricular dysfunction.

Deep Y-Descent in Right Atrial Waveforms Following Left Ventricular Assist Device Implantation.

BACKGROUND: Characterization of right heart catheterization (RHC) waveforms provides diagnostic and clinical information in heart failure patients. We aimed to investigate the implication of RHC waveforms, specifically the y-descent, in patients with left ventricular assist device (LVAD). METHODS AND RESULTS: Patients underwent RHC and waveforms were quantified prior to and 6 months after LVAD implantation. The impact of a deep y-descent (>3 mmHg) on echocardiographic measures of right heart function and 1-year hemocompatibility-related adverse event rates were investigated. Eighty-nine patients (median 59 years old, 65 male) underwent RHC. RHC waveform showed unique changes following LVAD implantation, particularly an increase in the steepness of the y-descent. A post-LVAD deep y-descent was associated with reduced right ventricular function and enlarged right heart. Patients with post-LVAD deep y-descent had higher rates of gastrointestinal bleeding (0.866 vs 0.191 events/year) and stroke (0.199 vs 0 events/year) compared with those without (P< .05 for both). CONCLUSION: RHC waveforms characterized by deep y-descent on RHC waveform during LVAD support was associated with impaired right ventricular function and worse clinical outcomes.

Hypogammaglobulinemia following heart transplantation: Prevalence, predictors, and clinical importance.

Hypogammaglobulinemia (HGG) can occur following solid organ transplantation. However, there are limited data describing the prevalence, risk factors, and clinical outcomes associated with HGG following heart transplantation. We retrospectively reviewed data of 132 patients who had undergone heart transplantation at our institution between April 2014 and December 2018. We classified patients into three groups based on the lowest serum IgG level post-transplant: normal (≥700 mg/dL), mild HGG (≥450 and <700 mg/dL), and severe HGG (<450 mg/dL). We compared clinical outcomes from the date of the lowest IgG level. Mean age was 57 (47, 64) years, and 94 (71%) patients were male. Prevalence of severe HGG was the highest (27%) at 3-6 months following heart transplantation and then decreased to 5% after 1 year. Multivariate analysis showed that older age and Caucasian race were independent risk factors for HGG. Overall survival was comparable between the groups; however, survival free of infection was 73%, 60%, and 45% at 1 year in the normal, mild HGG, and severe HGG groups, respectively (P = .013). In conclusion, there is a high prevalence of HGG in the early post-heart transplant period that decreases over time. HGG is associated with an increased incidence of infection.

Impact of Hospital Practice Factors on Mortality in Patients Hospitalized for Heart Failure in Japan　- An Analysis of a Large Number of Health Records From a Nationwide Claims-Based Database, the JROAD-DPC.

BACKGROUND: An inverse relationship exists between hospital case volume and mortality in patients with heart failure (HF). However, hospital performance factors associated with mortality in HF patients have not been examined. We aimed to identify these using exploratory factor analysis and assess the relationship between these factors and 7-day, 30-day, and in-hospital mortality among HF patients in Japan.Methods and Results:We analyzed the records of 198,861 patients admitted to 683 certified hospitals of the Japanese Circulation Society between 2012 and 2014. Records were obtained from the nationwide database of the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC). Using exploratory factor analysis, 90 hospital survey items were grouped into 5 factors, according to their collinearity: "Interventional cardiology", "Cardiovascular surgery", "Pediatric cardiology", "Electrophysiology" and "Cardiac rehabilitation". Multivariable logistic regression analysis was performed to determine the association between these factors and mortality. The 30-day mortality was 8.0%. Multivariable logistic regression analysis showed the "Pediatric cardiology" (odds ratio (OR) 0.677, 95% confidence interval [CI]: 0.628-0.729, P<0.0001), "Electrophysiology" (OR 0.876, 95% CI: 0.832-0.923, P<0.0001), and "Cardiac rehabilitation" (OR 0.832, 95% CI: 0.792-0.873, P<0.0001) factors were associated with lower mortality. In contrast, "Interventional cardiology" (OR 1.167, 95% CI: 1.070-1.272, P<0.0001) was associated with higher mortality. CONCLUSIONS: Hospital factors, including various cardiovascular therapeutic practices, may be associated with the early death of HF patients.

Optimal cannula positioning of HeartMate 3 left ventricular assist device.

Cannula position in HeartMate II and HeartWare left ventricular assist devices (LVADs) is associated with clinical outcome. This study aimed to investigate the clinical implication of the device positioning in HeartMate 3 LVAD cohort. Consecutive patients who underwent HeartMate 3 LVAD implantation were followed for one year from index discharge. At index discharge, chest X-ray parameters were measured: (a) cannula coronal angle, (b) height of pump bottom, (c) cannula sagittal angle, and (d) cannula lumen area. The association of each measurement of cannula position with one-year clinical outcomes was investigated. Sixty-four HeartMate 3 LVAD patients (58 years old, 64% male) were enrolled. In the multivariable Cox regression model, the cannula coronal angle was a significant predictor of death or heart failure readmission (hazard ratio 1.27 [1.01-1.60], P = .045). Patients with a cannula coronal angle ≤28° had lower central venous pressure (P = .030), lower pulmonary capillary wedge pressure (P = .027), and smaller left ventricular size (P = .019) compared to those with the angle >28°. Right ventricular size and parameters of right ventricular function were also better in the narrow angle group, as was one-year cumulative incidence of death or heart failure readmission (10% vs. 50%, P = .008). Narrow cannula coronal angle in patients with HeartMate 3 LVADs was associated with improved cardiac unloading and lower incidence of death or heart failure readmission. Larger studies to confirm the implication of optimal device positioning are warranted.

Future Perspectives of Intra-Aortic Balloon Pumping for Cardiogenic Shock.

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.

Aortic Insufficiency and Hemocompatibility-related Adverse Events in Patients with Left Ventricular Assist Devices.

AIM: Hemocompatibility-related adverse events (HRAE) are a major cause of readmissions in patients with left ventricular assist devices (LVAD). The impact of aortic insufficiency (AI) on HRAE remains uncertain. We aimed to investigate the impact of AI on HRAE. METHODS AND RESULTS: Patients who underwent LVAD implantation between August 2014 and July 2017 and had echocardiograms 3 months post-LVAD implantation were enrolled. AI severity was assessed by measuring the systolic/diastolic ratio of flow and the rate of diastolic flow acceleration using Doppler echocardiography of the outflow cannula. Regurgitation fraction was derived from these parameters. Significant AI was defined as regurgitation fraction > 30%. Among 105 patients (median age, 56 years; 76% male), 36 patients (34%) had significant AI. Baseline characteristics were statistically not significantly different between those with and without significant AI except for higher rates of ischemic etiology and atrial fibrillation in the significant AI group (P < 0.05 for both). One-year survival free from HRAE was 44% in patients with AI compared to 67% in patients without significant AI (P = 0.018). The average hemocompatibility score, which defines the net burden of HRAE, was higher in the AI group (1.72 vs 0.64; P = 0.009), due mostly to higher tier I (mild HRAE; P = 0.034) and tier IIIB scores (severe HRAE; P = 0.011). CONCLUSION: Significant AI, as assessed by Doppler echocardiographic parameters, was associated with HRAE during LVAD support.

Jarvik 2000 axial flow ventricular assist device in right single ventricle after Fontan operation.

We present a case of successful ventricular assist device support in a 13-year-old female diagnosed with right single ventricle, asplenia, dextrocardia, who had undergone a Fontan operation at 4 years old in an associated children hospital. She underwent placement of Jarvik 2000 axial flow ventricular assist device to the morphologic right ventricle which worked as systemic ventricle. The postoperative course was not eventful. She was waiting for heart transplantation attending high school 3 years after implantation.

Cilostazol Is Useful for the Treatment of Sinus Bradycardia and Associated Hemodynamic Deterioration Following Heart Transplantation.

Bradycardia is a common complication at the early postoperative period after heart transplantation (HT). The heart rate (HR) usually recovers within a few weeks; however, several patients need a temporary pacemaker or chronotropic agents to stabilize their hemodynamics. Here, we report the first case of transient bradycardia associated with hemodynamic deterioration following HT, which was successfully treated with cilostazol, a phosphodiesterase-3-inhibiting agent. A 59-year-old man received HT for advanced heart failure due to ischemic cardiomyopathy. General fatigue persisted even after the HT. His HR was around 60 beats per minute (bpm) with sinus rhythm. Echocardiography showed no abnormal findings. Right heart catheterization showed that the cardiac index (CI) was 1.9 L/minute/m2. Continuous intravenous infusion of isoproterenol (0.003 µg/kg/minute) increased the HR to 80 bpm and CI to 2.7 L/minute/m2 and improved his symptoms. Isoproterenol was switched to oral administration of cilostazol (100 mg, twice a day), which maintained the HR at around 80 bpm and CI of 2.5 L/minute/m2. The patient's HR gradually recovered and cilostazol could be discontinued three months after the HT. Oral administration of cilostazol can be a therapeutic option for patients with sinus bradycardia following HT, who need positive chronotropic support.

Flow Pattern of Outflow Graft is Useful for Detecting Pump Thrombosis in a Patient with Left Ventricular Assist Device.

Pump thrombosis (PT) is a serious complication after continuous-flow left ventricular assist device (LVAD) implantation. To detect PT, echocardiographic ramp test using left ventricular end-diastolic diameter (LVEDD) is known to be useful. However, this method has several limitations. In this study, we propose an alternative novel ramp test using the flow velocity of outflow graft (OG). A 46-year-old man underwent continuous-flow LVAD (HeartMate II, Abbott Laboratories, Lake Forest, IL, USA) implantation for advanced heart failure due to idiopathic dilated cardiomyopathy. About 2 years after implantation, he suffered from hemolysis and symptoms of heart failure, and PT was strongly suspected. The change in LVEDD was minimal with increase in pump speed (-0.06 cm/400 rotations per minute (rpm)), suggesting PT. The systolic to diastolic velocity (S/D) ratio of OG flow, which we proposed as a new indicator of PT, also showed minimal change (-0.07/400 rpm). His clinical symptoms improved with anticoagulation therapy, and the changing slope of the S/D ratio dramatically improved to -0.92/400 rpm. Although its consistency should be verified in many other cases, this novel method can be useful for detecting PT and evaluating its clinical course.