Impact of long-term optimizing atrioventricular delay using device-based algorithms on cardiac resynchronization therapy.

Sub-optimal atrioventricular delay (AVD) is one of the main causes of non-responder for cardiac resynchronization therapy (CRT). Recently, device-based algorithms (DBAs) that provide optimal AVD based on intracardiac electrograms, have been developed. However, their long-term effectiveness is still unknown. This study aims to investigate the effect of optimizing AVD using DBAs over a long period, on the prognosis of patients undergoing CRT. A total of 118 patients who underwent CRT at our hospital between April 2008 and March 2018, were retrospectively reviewed; 61 of them with optimizing AVD using DBAs were classified into the treated group (group 1), and the remaining 57 were classified into the control group (group 2). The median follow-up period was 46.0 months. The responder and survival rate in group 1 were significantly better than those in group 2 (group 1 vs. group 2: responder rate = 64% vs. 46%, p = 0.046; survival rate: 85.2% vs. 64.9%, p = 0.02). Moreover, investigating only the non-responder population showed that group 1 had an improved survival rate compared to group 2 (group 1 vs. group 2 = 72.7% vs. 45.1%, p = 0.02). Optimizing AVD using DBAs was a significant contributor to the improved survival rate in CRT non-responders in multivariate analysis (HR 3.6, p = 0.01). In conclusion, the long-term optimizing AVD using DBAs improved the survival rate in CRT and the prognosis of CRT non-responders, as well.

Chest computer tomography is safe without additional interrogation or monitoring for modern cardiac implantable electrical devices.

INTRODUCTION: Whether diagnostic computed tomography (CT) scans to cardiac implantable electronic devices (CIED) is safe in recent models remains unknown. METHODS: A two-centers observational study. Over 14 years, consecutive 2362 chest CT scans (1666 pacemakers [PMs], 145 cardiac resynchronization therapy PM, 316 implantable cardioverter-defibrillator, and 233 cardiac resynchronization therapy defibrillator) were interrogated and monitored upon imaging. RESULTS: Electromagnetic interference occurred only in a few old models: InSync 8040 (n = 14), InSync III Marquis (n = 1), and Kappa (n = 4), which resulted no adverse events. CONCLUSION: CIEDs, especially recent ones, are confirmed safe on chest CT.

Ablation characteristics and incidence of steam pops with a novel, surface temperature-controlled ablation system in an ex vivo experimental model.

BACKGROUND: A novel irrigation catheter (QDOT MICRO™) has been introduced, which enables a surface temperature-controlled ablation combined with tip cooling. However, the detailed description of its complex behavior and effect on the incidence of pops and lesion formation remains elusive. This study aimed to systematically investigate the ablation characteristics, feedback behavior, and incidence of steam pops in a simplified ex vivo swine model. METHODS: Using swine ventricular tissue perfused with saline at 37°C, we systematically created lesions with 4×3 combinations of the wattage (20, 30, 40, and 50 W) and contact force (CF, 10, 30, and 50 g). Ablation was continued for either 120 s or until a steam pop occurred and repeated 10 times with each setting. The lesion geometry, ablation index, feedback dynamics, and conditions underlying the steam pops were measured and analyzed. RESULTS: Steam pops occurred particularly frequently in combinations of a low CF and high power (10 g vs. 30 g+50 g [p < .0001]; 40 W+50 W vs. 20 W+30 W [p < .0001]). Failure to activate a feedback process was associated with a 5.1 times higher incidence of steam pops (21/109 vs.11/11, [95% CI 3.499-7.716], p < .0001). The wattage feedback was particularly evident with a high CF (30 and 50 g) and high initial wattage (40 and 50 W). The average delivered wattage at 27 W predicted the occurrence of steam pops. CONCLUSION: The temperature-controlled ablation with the QDOT MICRO™ demonstrated a complex feedback behavior, which contributed to a reduced incidence of steam pops and prolonged lead time to the pops.

Characteristics and optimal ablation settings of a novel, contact-force sensing and local impedance-enabled catheter in an ex vivo perfused swine ventricle model.

BACKGROUND: Local impedance (LI) has emerged as a new technology that informs on electrical catheter-tissue coupling during radiofrequency (RF) ablation. Recently, IntellaNav StablePoint, a novel LI-enabled catheter that equips contact force (CF) sensing, has been introduced. Although StablePoint and its predecessor IntellaNav MiFi OI share the common technology that reports LI, distinct mechanics for LI sensing between the two products raise a concern that the LI-RF lesion formation relationship may differ. METHODS: In an ex vivo swine cardiac tissue model, we investigated the initial level and range of a reduction in LI during a 60-s RF ablation and the resultant lesion characteristics at nine combinations of three energy power (30, 40, and 50 W) and CF (10, 30, and 50 g) steps. Correlations and interactions between CF, LI, wattage, and formed lesions were analyzed. Incidence of achieving LI drop plateau and that of a steam pop were also determined. RESULTS: Positive correlations existed between CF and initial LI, CF and absolute/relative LI drop, CF and lesion volume, and LI drop and lesion volume. At the same LI drop, wattage-dependent gain in lesion volume was observed. Steam pops occurred in all CF steps and the prevalence was highest at 50 W. LI drop predicted a steam pop with a cutoff value at 89Ω. CONCLUSION: In StablePoint, wattage crucially affects LI drop and lesion volume. Because 30 W ablation may by underpowered for intramural lesion formation and 50 W often resulted in a steam pop, 40 W appears to achieve the balance between the safety and efficacy.

The optimal ablation setting for a local impedance guided catheter in an in vitro experimental model.

BACKGROUND: The local impedance (LI) reflects the electrical catheter-tissue coupling and correlates with the local tissue temperature. However, there have been few clinical studies showing the recommended method for LI monitoring catheters. This study aimed to investigate the optimal ablation setting for this catheter in an in vitro experimental model. METHODS: LI monitoring catheters were used in an excised swine heart experimental model. The tissue contact force (CF) was directly monitored from an external weight scale. Radiofrequency ablation was performed with a combination of various energy power settings (30, 40, and 50 W), and various CFs (10, 30, and 50 g) for 60 s. The correlation between the LI-related indexes, power, and CF with the lesion formation was statistically analyzed. RESULTS: A positive correlation between the LI or lesion formation and CF was observed under all powers. Although the LI drop always correlated with the maximum lesion depth, lesion diameter, and lesion volume, the coefficient of the correlation value was lower under a high CF (lesion depth, diameter, and volume; 10 g, r = 0.8064, r = 0.8389, r = 0.8477; 30 g, r = 0.7590, r = 0.8063, r = 0.8060; 50 g r = 0.5555, r = 0.5701, and r = 0.5678, respectively). Steam pops occurred only under a 50 W ablation and the LI drop cutoff value for steam pops was 46 Ω. CONCLUSION: The same LI drop did not always lead to the same lesion size when the CF differed. Monitoring the LI and not exceeding 46 Ω would be useful for a safe ablation.

Ultrahigh density atrio-ventricular dual-chamber mapping as a next generation tool for ablation of accessory pathways.

INTRODUCTION: Detailed three-dimensional (3D) mapping has been useful for effective radiofrequency catheter ablation. The Rhythmia system can create atrio-ventricular dual-chamber mapping, which reveals the atrial and ventricular potentials all at once in the same map. The aim of this study was to investigate the utility of mapping the atrium and ventricle simultaneously with a high-density 3D mapping system for the ablation of accessory pathways (AP). METHODS: From July 2015 to August 2020, 111 patients underwent ablation of APs. Dual-chamber maps were created in 50 patients (median age 15 [10-54], 32 male [64.0%]), while 61 patients underwent radiofrequency (RF) ablation with conventional single-chamber 3D maps. The background characteristics and procedural details were compared between the dual-chamber mapping group and the conventional single-chamber mapping group. RESULTS: The number of RF applications (median [IQR]; 1.0 [1.0-3.0] vs. 3.0 [1.0-6.0], p = .0023), RF time (median [IQR], s; 9.2 [2.0-95.7] vs. 95.6 [4.1-248.7], p = .0107), and RF energy (median [IQR], J; 248.4 [58.7-3328.2] vs. 2867.6 [134.2-7728.4], p = .0115) were significantly lower in the dual-chamber group. The fluoroscopy time (median [IQR], min; 19.9 [14.2-26.1] vs. 26.5 [17.7-43.4], p = .0025) and fluoroscopy dose (median [IQR], mGy; 52.5 [31.3-146.0] vs. 119.0 [43.7-213.5], p = .0249) were also significantly lower in the dual-chamber than single-chamber mapping group. CONCLUSION: The dual-chamber mapping was useful for ablating accessory pathways and reducing the number of RF applications, total RF energy, and radiation exposure as compared with traditional mapping techniques.

Feasibility of simultaneous 99mTc-tetrofosmin and 123I-BMIPP dual-tracer imaging with cadmium-zinc-telluride detectors in patients undergoing primary coronary intervention for acute myocardial infarction.

BACKGROUND: Simultaneous dual-tracer imaging using isotopes with close photo-peaks may benefit from improved properties of cadmium-zinc-telluride (CZT)-based scanners. METHODS: Thirty patients having undergone primary percutaneous coronary intervention for acute myocardial infarction underwent single-(99mTc-tetrofosmin (TF) or 123I-BMIPP first) followed by simultaneous 99mTc-TF /123I-BMIPP dual-tracer imaging using a Discovery NM/CT 670 CZT. The values for the quantitative gated-SPECT (QGS) and the quantitative perfusion SPECT (QPS) were assessed. RESULTS: The intra-class correlation (ICC) coefficients between the single- and dual-tracer imaging were high in all the QGS and QPS data (Summed motion score: 0.95, summed thickening score: 0.94, ejection fraction: 0.98, SRS for 99mTc-TF: 0.97/ for 123I-BMIPP: 0.95). Wall motion, wall thickening and rest scores per coronary-territory-based regions were also comparable between the single- and dual imaging (ICC coefficient > 0.91). The interrater concordance in the visual analysis for the infarction and perfusion-metabolism mismatch was significant for the global and regional left ventricle (P < 0.001). CONCLUSION: The quantitative/semi-quantitative values for global and regional left-ventricular function, perfusion, and fatty acid metabolism were closely comparable between the dual-tracer imaging and the single-tracer mode. These data suggests the feasibility of the novel CZT-based scanner for the simultaneous 99mTc-TF /123I-BMIPP dual-tracer acquisitions in clinical settings.

The Predictive Value of Changes in Body Mass Index for the Incidence of Device-Specific Infections in Patients With Implantable Left Ventricular Assist Devices.

BACKGROUND: Implantable left ventricular assist devices (LVAD) have improved quality of life and survival in patients with advanced heart failure. However, LVAD-specific infections and predicting which patients will develop infections remain challenging. This study investigated whether changes in body mass index (BMI) during hospitalization following LVAD implantation are associated with LVAD-specific infections within 1 year of implantation.Methods and Results:Patients (n=135) undergoing LVAD implantation were retrospectively divided into 2 groups based on changes in BMI from LVAD implantation to discharge: those with and without decreases in BMI. Each group was further subdivided according to baseline albumin concentrations (high [>3.7 g/dL] and low [≤3.7 g/dL]). Twenty patients developed LVAD-specific infections within 1 year. Receiver operating characteristic curve analysis resulted in a ∆BMI cut-off of less than -0.128 kg/m2. In multivariate analysis, younger patients and those with decreases in BMI had significantly higher rates of LVAD-specific infection (P=0.010 and P=0.035, respectively). LVAD-specific infection rates were significantly higher for patients with low albumin and decreases in BMI than for patients with low albumin but no decrease in BMI. CONCLUSIONS: Decreases in BMI during hospitalization after LVAD implantation and younger age were independently associated with LVAD-specific infection within 1 year. Strict patient management may be needed to avoid decreases in BMI during hospitalization after LVAD implantation, particularly in patients with low baseline albumin concentrations.

Transvenous lead performance of implantable cardioverter-defibrillators and pacemakers.

BACKGROUND: After the reports of recalled leads, several technological improvements have been introduced and the durability of implantable cardioverter defibrillator (ICD) leads has improved. The incidence of lead failures is now less than in the previous studies. However, there are few reports that have shown the long-term durability of ICD leads as compared to pacemaker (PM) leads. This study analyzed the medium to long-term performance of transvenous ICD leads as compared to PM leads. METHODS: We retrospectively studied 1227 cases from April 2007 to December 2017 who underwent an initial transvenous ICD or PM implantation. The number of lead failures and patient background characteristics were analyzed. RESULTS: During a median 3-3.5 years follow up period, 1 (0.3%) ICD lead and 18 (2.4%) PM leads failed. The incidence of lead failures was significantly higher in the PM group than ICD group (p = .019). Males were associated with a higher incidence of lead failures in the PM group. CONCLUSION: Since the era of recalled ICD leads, the durability of ICD leads has remarkably improved and the incidence of lead failures with non-recalled ICD leads has been less than that for PM leads.

Development of a High-Efficacy Reprogramming Method for Generating Human Induced Pluripotent Stem (iPS) Cells from Pathologic and Senescent Somatic Cells.

Induced pluripotent stem (iPS) cells are a type of artificial pluripotent stem cell induced by the epigenetic silencing of somatic cells by the Yamanaka factors. Advances in iPS cell reprogramming technology will allow aging or damaged cells to be replaced by a patient's own rejuvenated cells. However, tissue that is senescent or pathologic has a relatively low reprogramming efficiency as compared with juvenile or robust tissue, resulting in incomplete reprogramming; iPS cells generated from such tissue types do not have sufficient differentiation ability and are therefore difficult to apply clinically. Here, we develop a new reprogramming method and examine it using myofibroblasts, which are pathologic somatic cells, from patient skin tissue and from each of the four heart chambers of a recipient heart in heart transplant surgery. By adjusting the type and amount of vectors containing transcriptional factors for iPS cell reprogramming, as well as adjusting the transfection load and culture medium, the efficiency of iPS cell induction from aged patient skin-derived fibroblasts was increased, and we successfully induced iPS cells from myocardial fibroblasts isolated from the pathologic heart of a heart transplant recipient.

Erratum: Differential Atrial Pacing to Detect Reconnection Gaps After Pulmonary Vein Isolation in Atrial Fibrillation.

The errors in the following list appeared in the article entitled "Differential Atrial Pacing to Detect Reconnection Gaps After Pulmonary Vein Isolation in Atrial Fibrillation" by Mai Tahara, Ritsushi Kato, Yoshifumi Ikeda, Koji Goto, So Asano, Hitoshi Mori, Shiro Iwanaga, Toshihiro Muramatsu, and Kazuo Matsumoto (Vol. 61, No. 3, 503-509, 2020).

Differential Atrial Pacing to Detect Reconnection Gaps After Pulmonary Vein Isolation in Atrial Fibrillation.

High-resolution mapping is useful to identify reconnection gaps in the pulmonary vein after pulmonary vein isolation for atrial fibrillation. However, it is sometimes difficult to differentiate pulmonary vein potentials from far-field potentials because of very low amplitudes. Our purpose was to evaluate the usefulness of a novel differential atrial pacing method to differentiate reconnected pulmonary vein potentials from isolated pulmonary vein potentials. This retrospective observational study included 34 patients with atrial fibrillation (22 men; mean age, 64 ± 14 years; 28 with paroxysmal atrial fibrillation) who underwent radiofrequency or cryoballoon ablation. Following pulmonary vein isolation, we created a high-resolution activation map during pacing from both the coronary sinus and left atrial appendage. We compared the characteristics of the pulmonary vein potentials and the pattern of activation between the reconnected and isolated pulmonary veins. We analyzed 131 pulmonary veins and found reconnections in 41 pulmonary veins (R group); 90 pulmonary veins had no reconnection (NR group). The R group had a significantly shorter distance between the earliest pulmonary vein activation sites in both activation maps, compared with the NR group (5.22 ± 0.53 mm versus 17.08 ± 0.36 mm, respectively; P < 0.0001). The amplitude of the pulmonary vein potentials was higher in the R group versus the NR group (0.61 ± 0.05 mV versus 0.04 ± 0.03 mV, respectively; P < 0.0001). Six gaps (14%) in the R group that were unrecognized using a conventional method were identified using our novel method. In conclusion, differential atrial pacing was useful to identify pulmonary vein reconnection gaps during ablation using a novel high-resolution mapping system.

Myopotential Oversensing Is a Major Cause of Inappropriate Shock in Subcutaneous Implantable Defibrillator in Japan.

Previous study has identified marked differences in patient characteristics and causes of inappropriate shock (IAS) between Japan and the Western societies in terms of subcutaneous implantable cardioverter-defibrillator (S-ICD). However, evidence of IAS in Asian populations including Japan has been limited to one observational study.Thus, we conducted a single-center registry study that tracks the postoperative course of 61 consecutive patients who received S-ICD from February 2016 to January 2020. Our findings showed that IAS occurred in 9.8% of the study population (6/61), which is comparable to the previously reported incidence. Remarkably, T-wave oversensing did not result in an IAS (0/6). Instead, myopotential oversensing was determined to have caused the most IAS events (4/6), while atrial fibrillation ranked second (2/6). A provocation maneuver (e.g., abdominal clench, push-ups, lifting a heavy item) reproduced myopotential noise disguised as R-waves, which should potentially trigger an IAS if uninterrupted. R-wave amplitude of the IAS group appeared relatively low compared to that of the non-IAS group although this finding was not tested significant. Furthermore, no temporal changes were noted in R-wave amplitude between the time of implantation and IAS events, suggesting that it is neither constantly low nor acutely dropped R-wave amplitude but a relatively high noise level that drives IAS. All the myopotential-IAS patients were found to be male. Right-sided lead implantation was associated with a higher incidence of IAS.This study highlights the fact that IAS continues to occur due to myopotential noise oversensing instead of T-wave oversensing. To minimize the risk of IAS, it is desirable to search and secure high R-wave voltage.

Acute Myocardial Infarction in an Adolescent Receiving Anagrelide for Essential Thrombocythemia with Underlying Persistent Coronary Endothelial Dysfunction.

Essential thrombocythemia (ET) is a Philadelphia chromosome-negative myeloproliferative disorder that is characterized by the overproduction of platelets and a marked increase in the numbers of mature megakaryocytes present in the bone marrow. Thrombohemorrhagic disorders are major morbidities of ET, especially those with mutations in the gene encoding Janus kinase 2 (JAK2). In this study, we report the case of an 18-year-old patient with ET carrying JAK2 mutation who developed acute ST-elevation myocardial infarction (STEMI) 5 months after a commencement of anagrelide. Coronary endothelial dysfunction confirmed by positive acetylcholine provocation test lasted a year after the occurrence of STEMI. Furthermore, intracoronary imaging using optical coherence tomography demonstrated non-atheromatous intimal fibrosis possibly due to chronic endothelial damage. The coronary pathologies reflected chronic change potentially associated with properties of ET and JAK2 mutation in addition to hyperviscosity. These observations suggest that the side effect of anagrelide in our patient was considered causative, while underlying chronic endothelial dysfunction and adverse endothelial remodeling may be predisposing factors to his fatal cardiovascular events.

Percutaneous Simple Lead Traction Is a Feasible and Effective Method for Right Ventricular Lead Perforations.

Right ventricular (RV) lead perforations are relatively rare but a potentially life-threatening complication of surgical implantations of cardiac implantable electronic devices (CIEDs). The result of percutaneous simple lead traction after lead perforations in the Japanese population has not been well clarified.We retrospectively studied 1359 patients (pacemakers [PMs], 973 patients; implantable cardioverter defibrillators [ICD], 386 patients) from April 2007 to December 2018 who underwent initial CIED implantation. Fifteen patients (1.1%) were diagnosed with RV lead perforations. The clinical data were evaluated in those patients, and the baseline characteristics and echocardiographic data were compared between the lead perforation group and the non-perforation group. The success and complication rates of the simple traction and repositioning of the RV lead were also assessed.The number of perforated RV leads was seven ICD leads (1.8%) and eight PM leads (0.82%). They were diagnosed on a median seven days (5.5-36.0) after the CIED implantation. Twelve patients were asymptomatic but were detected by an increased capture threshold. Three patients had pericarditis and stimulation of the diaphragm. Only one patient in the ICD lead group who took anticoagulants had a cardiac tamponade and needed an urgent pericardiocentesis (0.07%). No one required a thoracotomy or other devices related to complications after repositioning the RV lead. There was no significant difference in the baseline characteristics and echocardiographic parameters between the groups.RV lead perforations were relatively rare complications of CIED implantations. Percutaneous simple lead traction and repositioning the perforated lead was feasible and effective if the patients did not receive anticoagulants.

Influence of various energy settings and overlap ratios on size and continuity of lesions in a laser balloon ablation in vitro model.

INTRODUCTION: The influence of power (Watt [W]) and total energy (Joule [J]) on lesion size and the optimal overlap ratio remain unclear in laser balloon (LB) ablation for atrial fibrillation. We aimed to evaluate lesion size and visible gaps after LB ablation with various energy settings and different overlap ratios in vitro model. METHODS AND RESULTS: Chicken muscles were cauterized using the first-generation LB with single applications of full and a half duration of six energy settings (5.5 W/30 seconds [165 J] to 12 W/20 seconds [240 J]) and varying power (5.5-12 W) at the constant total energy (160 J). Three overlapped ablations with different ratios (25% and 50%) for each energy setting were also performed to evaluate the visible gap degree categorized from 1 (perfect) to 3 (poor). Twenty lesions were evaluated for each energy setting. In single applications of full duration, lesion depth, lesion volume, and maximum lesion diameter increased according to the total energy (all, P < .001) and were greater than in those of half duration in each energy setting (all, P < .05). However, applications with larger power created larger lesion volume and maximum lesion diameter at constant total energy (P < .05). The visible gap degree was better in all energy settings with 50% overlapped ablation than in those with 25% (all, P < .001). CONCLUSION: Lesion size depends not only on power but also on total energy in the LB ablation. Sufficiently overlapped ablations allow continuous lesion formation.

Analysis of the heart rate variability during cryoballoon ablation of atrial fibrillation.

Aims: Vagal responses such as marked bradycardia or a rapid blood pressure decrease are often observed during pulmonary vein (PV) isolation of atrial fibrillation (AF) using a cryoballoon (CB). However, the relationship between the marked vagal response and change in the heart rate variability (HRV) as a marker of the autonomic tone is not well understood. Methods and results: Fifty-four paroxysmal AF patients underwent CB ablation. The CB ablation was started from the right sided PVs in 25 patients (R group) and left sided PVs in 29 (L group). The HRV and haemodynamic status during the procedure were analysed. A vagal response was observed in 16 L group patients (61.5%) during the ablation of the different PVs (RSPV:1, RIPV:5, LSPV:15, LIPV:5), while it was observed in only 2 R group patients (9.5%) (RSPV:0, RIPV:0, LSPV:1, LIPV:1) (P = 0.0002). The HRV in the L group was significantly higher than that in the R group just after the CB ablation especially for the left sided PVs (L group vs. R group, total power of the HRV, median; RSPV, 11184.7 vs. 4360.0, P = 0.21; RIPV, 9044.3 vs. 2115.1, P = 0.01; LSPV, 21186.0 vs. 1314.2, P = 0.0002; LIPV 10265.9 vs. 1236.2, P = 0.0007). Conclusion: A marked increase in the HRV parameters was observed just after the CB ablation. An initial CB ablation of the right PVs decreased the change in the autonomic tone during the right PV ablation and subsequent left PV ablation. It prevented an excessive vagal response during the CB ablation and might be a safe procedure.

Demeanor of rivaroxaban in activated/inactivated FXa.

Activated factor X (FXa) plays an important role in thrombin generation and inflammation. Factor X is not converted constitutively to FXa, but only after intrinsic clotting factors are activated and/or cellular injury occurs. Although rivaroxaban is one of direct FXa inhibitors, its function in the inactivated coagulation cascade is unclear. In human umbilical vein endothelial cells that natively express protease-activated receptor-1 and -2, high dose rivaroxaban did not alter gene transcripts including pro-inflammatory genes in DNA microarray. Upon FXa stimulation, the expressions of pro-inflammatory genes such as monocyte chemoattractant protein-1 (MCP-1), intracellular adhesion molecule-1, and interleukin-8 were maximally increased at 4 h after stimulation, and were suppressed by rivaroxaban. To confirm these results, quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) for MCP-1 were performed. FXa evoked the expression of MCP-1 maximally at 4 h after stimulation, whereas MCP-1 displayed a different temporal activation in ELISA. Interestingly, rivaroxaban inhibited both time courses of MCP-1 expression. These results suggest that rivaroxaban may not influence gene modulation in the inactivated coagulation state, but can attenuate the endothelial damage evoked by FXa and pro-inflammatory cytokine genes.

Waon Therapy for Managing Chronic Heart Failure　- Results From a Multicenter Prospective Randomized WAON-CHF Study.

BACKGROUND: Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. METHODS AND RESULTS: In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. CONCLUSIONS: Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF.