Rationale and study design of the GOREISAN for heart failure (GOREISAN-HF) trial: A randomized clinical trial.

BACKGROUND: The decongestion strategy using loop diuretics is essential for improving signs and symptoms of heart failure (HF). However, chronic use of loop diuretics in HF has been linked to worsening renal function and adverse clinical outcomes in a dose-dependent manner. Goreisan, a traditional Japanese herbal medicine, has a long history of use in Japan for regulating body fluid homeostasis and has been recognized as causing less adverse outcomes such as dehydration in contrast to loop diuretics in clinical practice. Therefore, we designed the GOREISAN-HF trial to evaluate the long-term effects of a new decongestion strategy adding Goreisan to usual care in patients with HF and volume overload. METHODS: The GOREISAN-HF trial is an investigator-initiated, multicenter, pragmatic, randomized, comparative effectiveness trial in which we will enroll 2,192 patients hospitalized for HF at 68 hospitals in Japan. All study participants will be randomly assigned to either a decongestion strategy that adds Goreisan at a dose of 7.5 g daily on top of usual care or usual care alone. Investigators have the flexibility to change the existing diuretic regimen in both groups. The primary end point is the improvement rate of cardiac edema at 12-month follow-up, and the co-primary end point is a composite of all-cause death or hospitalization up to the end of the planned follow-up period. Secondary end points include longitudinal changes in patient-reported outcomes, loop diuretics dose, and renal function. CONCLUSIONS: The GOREISAN-HF is the first large-scale randomized pragmatic trial to assess the efficacy and safety of a new congestion control strategy adding Goreisan to usual care in patients with HF and volume overload. REGISTRATION NUMBER: NCT04691700.

Reproducibility and stability of atrial fibrillation drivers identified by an automated algorithm: CARTOFINDER.

BACKGROUND: The characteristics of atrial fibrillation (AF) drivers identified by CARTOFINDER have not been thoroughly evaluated. Therefore, the current study was sought to validate the reliability of AF drivers. METHODS: The reliability of focal and rotational activation identified by CARTOFINDER during AF was assessed by the sequential recordings in each site before and after pulmonary vein isolation (PVI) in 27 persistent AF patients. The primary outcome measures were the reproducibility rate during the sequential recordings and the stability rate between pre- and post-PVI. RESULTS: Among 32,135 points in 509 sites, focal activation was identified in 1775 points (5.5%) with a repetition of 11 (6-26) times during the recording. Rotational activation was identified in 132 points (0.4%) with a repetition number of 21 (14-21) times. AF drivers had significantly higher voltage and shorter AF cycle length than non-AF driver sites. The reproducibility rate of focal activation during the sequential recordings was 57.8% and increased with the repetition number. The reproducibility rate of rotational activation was 37.4%. The prevalence and the reproducibility rate of focal activation in post-PVI were significantly lower than pre-PVI (5.3% versus 6.0%, P = 0.02; 53.4% versus 63.6%, P < 0.001). The stability rate of focal activation between pre- and post-PVI was only 28.3% but increased with the repetition number. There was no stable rotational activation between pre- and post-PVI. CONCLUSIONS: The reproducibility of AF drivers, especially focal activation, identified by CARTOFINDER is relatively favorable, but the stability between pre- and post-PVI was poor. These results depended on the repetition number during the recording.

Instability of rotational activation as atrial fibrillation drivers: Assessment by ExTRa Mapping system.

BACKGROUND: ExTRa Mapping™ has developed to visualize rotational activation as atrial fibrillation (AF) drivers. The current study was sought to evaluate the instability of AF drivers by ExTRa Mapping™. METHODS: Variation of nonpassively activated ratio (%NP) among three-time repetitive recordings before and after pulmonary vein isolation (PVI) in left atrium was assessed in 26 persistent AF patients. The recoding time was set at 5 or 8 s for the respective patients. The outcome measures included %NP at each recording, mean value of the three-time recordings, and the instability index, which was defined as maximum difference per mean %NP × 100 (%). RESULTS: Total 683 sites 2049 recordings were assessed. Mean %NP was 33.3(23.3-42.7)%, and higher in sites with severe (≥50%) and patchy low voltage area than those without, but not in those with severe complex fractionated atrial electrogram area. There was significant correlation between actual and mean %NP (R = 0.86, P < .001), but maximum difference among the repetitive recordings was 16(10-24)%. The instability index of %NP was 55.9(30.9-83.6)%, and significantly lower at the recordings of 8 s compared with 5 s (50.6[28.6-78.4]% vs. 60.4[35.0-90.0]%, P = .004). Furthermore, it was higher at sites with lower reliability of the recordings. After PVI, mean %NP significantly decreased (28.7[18.3-36.7]% vs. 37.7[28.7-45.7]%, P < .001), but the instability index significantly increased compared with those before PVI (60.0[35.0-92.7]% vs. 48.9[29.1-75.0]%, P = .001). CONCLUSION: Rotational activation as AF drivers assessed by ExTRa Mapping™ is unstable, and repetitive and longer recording is required for the reliable assessment even after PVI.

Kampo medicine for the holistic approach to older adults with heart failure.

Heart failure (HF) is a leading cause of hospitalization, morbidity, and mortality in older adults and represents a significant clinical and economic burden on the health care system. However, there are many challenges in assessing and managing HF in elderly patients, who often have coexisting multimorbidity, frailty, and malnutrition. Therefore, it is often difficult to solve these problems with Western medicine alone, and a holistic approach, including Kampo medicine, can be helpful. In particular, managing volume control and frailty by adding Kampo formulas may help improve health-related quality of life and substantially impact prognosis in HF. This review article summarizes the role of Kampo medicine for older patients with HF and frailty.

Optimal cutoff value of bipolar low-voltage in electroanatomic voltage mapping during atrial fibrillation rhythm.

BACKGROUND: Electroanatomic voltage mapping (EAVM) of the left atrium (LA) with multielectrodes is usually acquired during sinus rhythm (SR), and the feasibility of EAVM during atrial fibrillation (AF) rhythm is unclear. METHODS: We performed EAVM of LA during both SR and AF rhythm in 44 patients undergoing catheter ablation for AF and validated the optimal cutoff value of low-voltage area (LVA) during AF rhythm for detecting LVA defined as bipolar voltages ≤0.5 mV during SR. RESULTS: In each session, mean 829 and 552 points were acquired by multielectrodes during SR and AF rhythm, respectively. Mean proportion of LVA was 4.9% among LA surface area of 276.2 cm2 . Differences of LVA proportions between SR and AF rhythm were 5.8% (P < 0.001), 4.2% (P < 0.001), 2.7% (P < 0.001), 1.2% (P = 0.01), and -0.5% (P = 0.17) at the cutoff value of 0.4, 0.35, 0.3, 0.25, and 0.2 mV during AF rhythm, respectively. There was a good correlation between LVA proportions during SR and AF rhythm with cutoff value of 0.2 mV (R = 0.88, P < 0.001) and 37 patients (84.1%) had the discrepancy of LVA proportions within 3%. Furthermore, there was no significant difference between LVA proportions at each segment of LA. The discrepancy was relatively large in patients with large LA dimension and LVA during SR. CONCLUSION: EAVM during AF rhythm was feasible and the optimal cutoff value of LVA was 0.2 mV for detecting LVA ≤ 0.5 mV during SR. However, the evidence is restricted to patients with relatively small LVA.