Adult-onset idiopathic peripheral pulmonary artery stenosis.

BACKGROUND: Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS. METHODS: We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected. RESULTS: 44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40 mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514 dyn·s·cm-5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively. CONCLUSIONS: In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.

Therapeutic Strategy for Patients with Concomitant Pulmonary Artery Hypertension and Hypertrophic Obstructive Cardiomyopathy: A Rare Case Report.

Combined cases of hypertrophic obstructive cardiomyopathy (HOCM) and pulmonary arterial hypertension (PAH) are rare and have a management dilemma. Although preload is crucial in the management of HOCM, anti-PAH agents dramatically change the preload, leading to improving or worsening heart failure in patients with HOCM. We had a 74-year-old woman with Sjogren-syndrome-associated PAH. Her heart failure worsened following the initiation of anti-PAH agents due to an incremental preload on the left ventricle, whereas HOCM clinically developed following the termination of anti-PAH agents and progressing anorexia due to the progression of the left ventricular outflow obstruction. Careful monitoring of the left ventricular outflow obstruction during initiation/termination of anti-PAH agents and medical intervention to the HOCM are highly recommended.

Selexipag for the treatment of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remain limited. Selexipag, an oral selective IP prostacyclin receptor agonist approved for pulmonary arterial hypertension, is a potential treatment option for CTEPH. METHODS: In this multicentre, randomised, double-blind, placebo-controlled study, 78 Japanese patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and/or balloon pulmonary angioplasty were randomly assigned to receive placebo or selexipag. The primary end-point was the change in pulmonary vascular resistance (PVR) from baseline to week 20. Secondary end-points were changes in other haemodynamic parameters: 6-min walk distance (6MWD), Borg dyspnoea scale score, World Health Organization (WHO) functional class, EuroQol five-dimension five-level tool and N-terminal pro-brain natriuretic peptide. RESULTS: The change in PVR was -98.2±111.3 dyn·s·cm-5 and -4.6±163.6 dyn·s·cm-5 in the selexipag and placebo groups, respectively (mean difference -93.5 dyn·s·cm-5; 95% CI -156.8 to -30.3; p=0.006). The changes in cardiac index (p<0.001) and Borg dyspnoea scale score (p=0.036) were also significantly improved over placebo. 6MWD and WHO functional class were not significantly improved. The common adverse events in the selexipag group corresponded to those generally observed following administration of a prostacyclin analogue. CONCLUSION: Selexipag significantly improved PVR and other haemodynamic variables in patients with CTEPH, although exercise capacity remained unchanged. Further large-scale investigation is necessary to prove the role of selexipag in CTEPH.

Responders to Sodium-Glucose Cotransporter 2 Inhibitors in Improving Left Ventricular Function.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i)-incorporated medical therapy is associated with cardiac function improvement in patients with heart failure. However, the factors associated with such an improvement remain unknown.This study included patients with heart failure and type 2 diabetes mellitus who received SGLT2i-incorporated medical therapy in our institute. Transthoracic echocardiography was performed at baseline and 3-18 months later. The factors associated with cardiac function improvement were investigated.A total of 47 patients (median age, 69 years old; 35 men) were included in this study. SGLT2i was administered for median 284 days (range: 86-730 days). The left ventricular ejection fraction increased from 39.0% to 54.0% (P < 0.001), and the E/e' ratio decreased from 14.0 to 10.4 (P = 0.002). Younger age, higher serum albumin level, and lower serum sodium level were independently associated with an improvement in systolic function, defined as an increase in the ejection fraction of ≥ 35% among patients with systolic heart failure (P = 0.018). Male sex and impaired renal function tended to be associated with an improvement in diastolic function, defined as a decrease in the E/e' ratio of ≥ 20% among the overall cohort.Several factors were associated with improvements in systolic and diastolic functions during the SGLT2i-incorporated medical therapy.

Renoprotective effects of sodium glucose cotransporter 2 inhibitors in type 2 diabetes patients with decompensated heart failure.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of the composite renal endpoint and weakens the progressive decline in renal function in patients with chronic heart failure (HF). However, a detailed mechanism of SGLT2i on renal function and outcome remains uninvestigated. METHODS: We prospectively included 40 type 2 diabetic mellitus (T2DM) patients (median 68 years old, 29 male) who were hospitalized for decompensated HF and received SGLT2i during the index hospitalization. Of them, 24 patients had increases in estimated glomerular filtration rate (eGFR) at 12-month follow-up and 16 had decreases in eGFR. We investigated the baseline factors associating with the improvement in renal function. RESULTS: Lower plasma B-type natriuretic peptide (BNP) level and the use of renin-angiotensin system inhibitor (RASI) were independently associated with increases in eGFR during the follow-up period (p < 0.05 for both). Patients with both low plasma BNP levels and uses of RASI achieved significant increases in eGFR irrespective of the baseline HbA1c levels. CONCLUSIONS: Lower plasma BNP level and the use of RASI at baseline were the key factors contributing to the renoprotective effects of SGLT2i among patients with decompensated HF and T2DM.

Relationship Between HbA1c Level and Effectiveness of SGLT2 Inhibitors in Decompensated Heart Failure Patients with Type 2 Diabetes Mellitus.

The DAPA-HF trial demonstrated that sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced worsening heart failure (HF) events in chronic HF patients with or without type 2 diabetic mellitus (T2DM). However, it remains unclear whether the effectiveness of SGLT2i is also observed in patients with decompensated HF irrespective of HbA1c level. Eighty-one T2DM patients hospitalized due to decompensated HF were enrolled and divided into 2 groups according to their HbA1c levels (group H, HbA1c 6.9-13.0%, n = 41; group L, HbA1c < 6.9%, n = 40). After the initial management of HF, one of the SGLT2i (canagliflozin 100 mg/day or dapagliflozin 5 mg/day or empagliflozin 10 mg/day) was non-randomly administered, and clinical parameters associating with HF and T2DM were followed for 7 days. No symptomatic hypoglycemia was observed in any patient. In both groups, urine glucose excretion was increased significantly after the administration of SGLT2i. However, its amount was greater in group H than group L. Urine volume was increased significantly at day 1 in both groups. Urine volume returned to the baseline after one week in group L. In contrast, the increase in urine volume persisted at least for one week in group H. Of note, a decrease in B-type natriuretic peptide levels after the initiation of SGLT2i was observed in both groups similarly despite differences in urine output and excretion of urine glucose. In conclusion, SGLT2i can improve decompensated HF in patients with T2DM irrespective of the HbA1c level.

Efficacy of Continuing SGLT2 Inhibitors on Outcomes in Patients with Acute Decompensated Heart Failure.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) reduces mortality and morbidity in patients with chronic heart failure (HF). However, the clinical implication of SGLT2i therapy in patients with acute decompensated HF remains uncertain. We prospectively studied 86 type 2 diabetic mellitus (T2DM) patients (71.8 ± 12.1 years, 55 men) who were hospitalized for acute decompensated HF and received SGLT2i during the index hospitalization. Among the patients, 56 continued SGLT2i at discharge and 30 did not. The continued group experienced fewer HF re-hospitalizations than the discontinued group (24% versus 39%, P = 0.008) with a hazard ratio of 0.29 (95% confidence interval 0.10-0.85) adjusted for other significant potential confounders. In conclusion, long-term SGLT2i therapy might prevent unplanned HF re-hospitalization in patients with T2DM and acute decompensated HF.

Multicenter, Prospective Study on Respiratory Stability During Recovery From Deterioration of Chronic Heart Failure.

BACKGROUND: The respiratory instability frequently observed in advanced heart failure (HF) is likely to mirror the clinical status of worsening HF. The present multicenter study was conducted to examine whether the noble respiratory stability index (RSI), a quantitative measure of respiratory instability, reflects the recovery process from HF decompensation. Methods and Results: Thirty-six of 44 patients hospitalized for worsening HF completed all-night measurements of RSI both at deterioration and recovery phases. Based on the signs, symptoms, and laboratory data during hospitalization, the Central Adjudication Committee identified 22 convalescent patients and 14 patients with less extent of recovery in a blinded manner without any information on RSI or other respiratory variables. The all-night RSI in the convalescent patients was increased from 27.8±18.4 to 34.6±15.8 (P<0.05). There was no significant improvement of RSI, however, in the remaining patients with little clinical improvement. Of the clinical and laboratory variables, on stepwise linear regression modeling, body weight, peripheral edema, and lung congestion were closely related to the RSI of recovered patients and accounted for 56% of the changes in RSI (coefficient of determination, R2=0.56). CONCLUSIONS: All-night RSI, a quantitative measure of respiratory instability, could faithfully reflect congestive signs and clinical status of HF during the recovery process from acute decompensation.

Restrictive Lung Function Is Related to Sympathetic Hyperactivity in Patients With Heart Failure.

BACKGROUND: Sympathoexcitation and impaired lung function are common in patients with severe heart failure (HF). However, the association between impaired lung function and sympathoexcitation remains unknown. METHODS AND RESULTS: Muscle sympathetic nerve activity (MSNA) and clinical variables were determined in 83 HF patients with left ventricular ejection fraction (LVEF) <0.45. Restrictive and obstructive changes on spirometry were defined as reduced forced vital capacity (FVC) of <80% of predicted and a ratio of forced expiratory volume in the first second to FVC of <70%, respectively. Restrictive and obstructive changes were identified in 17 and 21 patients, respectively. MSNA was higher in patients with restrictive changes than in those without restrictive changes (84 vs 66 bursts per 100 beats; P < .01), but was similar in those with and without obstructive changes. Univariate analyses showed that FVC, estimated glomerular filtration rate (eGFR), specific activity scale, B-type natriuretic peptide level, LVEF, age, and use of aldosterone receptor blockers were significant predictors of MSNA burst incidence. Multivariate analysis revealed that FVC, LVEF, and eGFR were independent factors for increased burst incidence. Changes in FVC during follow-up negatively correlated with changes in burst rate (n = 11; P < .01). CONCLUSION: Restrictive lung function was associated with increased sympathetic nerve activity independently from HF severity.

Successful Withdrawal from Dobutamine by Canagliflozin in a Diabetic Patient with Stage D Heart Failure.

Patients with stage D heart failure (HF) frequently become dependent on high doses of diuretics and inotropic agents. Recently, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), an oral antidiabetic agent, has been demonstrated to have favorable effects in preventing HF. However, it remains unknown whether SGLT2i is reliable for patients with decompensated HF. We experienced a case of a patient with stage D HF for whom attempting intravenous dobutamine withdrawal was difficult even after the administration of all conventional pharmacological treatment. Administration of canagliflozin produced an additive diuretic action and correction of volume overload in combination with azosemide and tolvaptan, and resulted in successful withdrawal of dobutamine. Thus, SGLT2i might be promising for the treatment of patients with congestive HF who are refractory to conventional diuretic treatment.

Sympathetic Nerve Activity Efferent Drive and Beta-Blocker Treatment　- Effect of Interaction in Systolic Heart Failure.

BACKGROUND: Although both ß-blocker dose (BBD) and sympathetic activity efferent drive are associated with prognosis in chronic heart failure (HF), little is known about the prognostic value of the interaction between them. METHODS AND RESULTS: Potential prognostic variables including resting muscle sympathetic nerve activity (MSNA) were investigated in 133 patients with HF (ejection fraction [EF] <0.45). BBD was normalized to therapeutically equivalent doses of carvedilol. Primary cardiovascular endpoints included cardiovascular death and HF hospitalization. Predictors for outcomes were assessed on univariate, multivariate, and Kaplan-Meier analysis. EF was followed for 9 months after MSNA measurement in 102 patients. During the 1,419±824-day follow-up period, 24 patients died (sudden death, n=10; progressive HF, n=14). On multivariate Cox proportional hazard analysis, higher MSNA (P=0.037; HR, 2.01) and lower BBD (<5.0 mg/day; P=0.041; HR, 1.94) were independent predictors of cardiovascular events. Patients were divided into higher MSNA (≥64 bursts/100 beats) and lower MSNA groups. Although lower BBD remained an independent predictor in patients with higher MSNA, BBD was not statistically significant in patients with lower MSNA on univariate analysis. Additionally, there was a lower EF change in patients with lower BBD and higher MSNA. CONCLUSIONS: Higher BBD might be necessary to avoid cardiovascular events in HF patients with central sympathetic overactivation. (Circ J 2016; 80: 2149-2154).

Efficacy and Safety of a Novel Endothelin Receptor Antagonist, Macitentan, in Japanese Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Macitentan is a novel, dual endothelin receptor antagonist with sustained receptor binding, used for the long-term treatment of pulmonary arterial hypertension (PAH). In the present study, we assessed the efficacy and safety of macitentan in Japanese patients with PAH. METHODS AND RESULTS: Macitentan was administered at a once-daily dose of 10 mg in 30 patients. The primary endpoint was change in pulmonary vascular resistance (PVR) from baseline to week 24. Change to week 24 in the other hemodynamic parameters, 6-min walk distance (6MWD), World Health Organization (WHO) functional class, and plasmaN-terminal pro-brain natriuretic peptide (NT-pro-BNP), as well as time to clinical deterioration up to week 52 were also assessed as secondary endpoints. In the 28 patients on per-protocol analysis, PVR decreased from 667±293 to 417±214 dyn·sec·cm(-5)(P<0.0001). 6MWD increased from 427±128 to 494±116 m (P<0.0001). WHO functional class improved in 13 patients (46.4%) and was maintained in 15 patients (53.6%), and NT-pro-BNP was reduced by 18% (P<0.0001). The favorable treatment effect on PVR was apparent regardless of concomitant therapy for PAH. CONCLUSIONS: Macitentan was efficacious and well tolerated and improved the hemodynamic parameters, exercise capacity, symptoms, and clinical biomarkers in Japanese PAH patients. Macitentan can be a valuable therapeutic option for Japanese patients with PAH. ( TRIAL REGISTRATION: JAPIC Clinical Trials Information [JapicCTI-121986].) (Circ J 2016; 80: 1478-1483).

Slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with chronic heart failure: from modeling to clinical application.

Influences of slow and deep respiration on steady-state sympathetic nerve activity remain controversial in humans and could vary depending on disease conditions and basal sympathetic nerve activity. To elucidate the respiratory modulation of steady-state sympathetic nerve activity, we modeled the dynamic nature of the relationship between lung inflation and muscle sympathetic nerve activity (MSNA) in 11 heart failure patients with exaggerated sympathetic outflow at rest. An autoregressive exogenous input model was utilized to simulate entire responses of MSNA to variable respiratory patterns. In another 18 patients, we determined the influence of increasing tidal volume and slowing respiratory frequency on MSNA; 10 patients underwent a 15-min device-guided slow respiration and the remaining 8 had no respiratory modification. The model predicted that a 1-liter, step increase of lung volume decreased MSNA dynamically; its nadir (-33 ± 22%) occurred at 2.4 s; and steady-state decrease (-15 ± 5%), at 6 s. Actually, in patients with the device-guided slow and deep respiration, respiratory frequency effectively fell from 16.4 ± 3.9 to 6.7 ± 2.8/min (P < 0.0001) with a concomitant increase in tidal volume from 499 ± 206 to 1,177 ± 497 ml (P < 0.001). Consequently, steady-state MSNA was decreased by 31% (P < 0.005). In patients without respiratory modulation, there were no significant changes in respiratory frequency, tidal volume, and steady-state MSNA. Thus slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with high levels of resting sympathetic tone as in heart failure.

Differing effects of adaptive servoventilation and continuous positive airway pressure on muscle sympathetic nerve activity in patients with heart failure.

BACKGROUND: Long-term adaptive servoventilation (ASV) increases cardiac function more effectively than continuous positive airway pressure (CPAP), possibly via alleviation of sympathetic overactivation. The present study evaluated the effect of ASV and CPAP at comparable pressure on muscle sympathetic nerve activity (MSNA) in patients with heart failure (HF) and with or without periodic breathing (PB). METHODS AND RESULTS: A total of 57 patients with HF (ejection fraction <0.45) were randomized to receive CPAP (n=28) or ASV (n=29). Respiratory profiles and MSNA were continuously monitored before and during CPAP and ASV (30min) at pressures of 6.5 and 6.6cmH2O, respectively. The severity of respiratory instability was determined using the coefficient of variation of tidal volume (CV-TV). Although heart rate and blood pressure remained unchanged, only ASV improved CV-TV. MSNA decreased in the ASV (P<0.001), but not in the CPAP group. The change in CV-TV independently predicted changes in MSNA (P<0.001). Device type and PB significantly interacted with changes in MSNA (P<0.05) and ASV exerted sympathoinhibitory effects in patients with PB, whereas CPAP did not. A sympathoinhibitory effect in patients without PB was not evident in either treatment arm. CONCLUSIONS: ASV probably exerts its sympathoinhibitory effects in patients with HF and PB through pressure support.

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.

Effect of adaptive servoventilation on muscle sympathetic nerve activity in patients with chronic heart failure and central sleep apnea.

BACKGROUND: Adaptive servoventilation (ASV) improves cardiac function and sympathetic nerve activity in patients with heart failure (HF). However, the mechanisms underlying these improvements remain obscure. METHODS AND RESULTS: We compared muscle sympathetic nerve activity (MSNA) and cardiorespiratory polygraphy and echocardiography findings at baseline and at 3.5 ± 0.8 months' follow-up in 32 patients with HF (New York Heart Association functional class II or III; ejection fraction <45%) and central sleep apnea (CSA; apnea-hypopnea index [AHI] ≥15/h) who consented (n = 20; ASV group) or declined (n = 12; non-ASV group) to undergo ASV treatment. Compliance with ASV and changes in AHI were determined from data collected by integral counters in devices and from cardiorespiratory polygraphic findings, respectively. Ejection fraction and MSNA significantly changed in the ASV (both P < .001) but not the non-ASV group. Although changes in AHI and MSNA correlated, the average use of ASV did not. In contrast, changes in AHI and the average use of ASV were independent predictors of changes in ejection fraction (both P < .01). CONCLUSIONS: ASV decreases MSNA and improves cardiac function in association with suppression of CSA in patients with HF.

Anticoagulation control quality affects the D-dimer levels of atrial fibrillation patients.

BACKGROUND: Anticoagulation control quality affects the incidence of thromboembolic events in atrial fibrillation (AF) patients. However, the effects of anticoagulation control quality on the prothrombotic state of AF patients are unclear. METHODS AND RESULTS: Ninety-five AF patients who had been treated with warfarin were prospectively followed-up for 449 ± 92 days. We analyzed whether time in the therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time, percentage of INR values in the range (%INR), and coefficient of variation of INR values (CV-INR) were related to D-dimer levels. The mean values of TTR, %INR, and CV-INR were 62%, 59%, and 0.19, respectively, and their median values were 67%, 63%, and 0.19, respectively. TTR was significantly correlated with %INR (R(2) = 0.917, P<0.01), but not with CV-INR (R(2) = 0.050, P = 0.26). The mean and median D-dimer levels were 0.79 and 0.60 µg/ml, respectively. Low TTR, low %INR, and high CV-INR were found to contribute to high D-dimer levels (P = 0.02, 0.03, and 0.02, respectively). CONCLUSIONS: In AF patients treated with warfarin, not only the duration outside the target INR range, but also the fluctuation in INR level may influence the prothrombotic state.

Primary Cardiac Angiosarcoma Accompanying Cardiac Tamponade.

A de novo cardiac malignant tumor is rare and sometimes challenging to diagnose. We encountered a 67-year-old man without any medical history complaining of dyspnea on effort. On admission, his hemodynamics were deteriorated due to cardiac tamponade, which was improved by percutaneous drainage of 1,200 mL pericardial effusion, showing 11.0 g/dL of hemoglobin. We suspected primary cardiac malignancy following multidisciplinary tests, and a cardiac biopsy via sternotomy demonstrated the definitive diagnosis of primary malignant tumor (angiosarcoma) infiltrating the right atrial myocardium. We initiated weekly paclitaxel therapy. Further studies are warranted to establish the optimal diagnostic and therapeutic strategy for de novo cardiac malignancy.

Factors Associated with Recurrent Heart Failure during Incorporating SGLT2 Inhibitors in Patients Hospitalized for Acute Decompensated Heart Failure.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce the risk of hospitalization for heart failure (HF) or death from cardiovascular causes among patients with chronic HF. However, little is known about the specific factors associated with clinical events during SGLT2i therapy in patients hospitalized for acute decompensated heart failure (ADHF). Methods: Consecutive patients who were hospitalized for ADHF and received SGLT2i during the index hospitalization between February 2016 and April 2021 were retrospectively evaluated. We investigated the factors associated with recurrent hospitalization for HF during the SGLT2i therapy. Results: A total of 143 patients (median age 73 years, 92 men) were included. Estimated glomerular filtration rate (eGFR) was negatively associated with a primary endpoint with a hazard ratio of 0.94 (95% confidence interval 0.90−0.98, p = 0.007). Those with lower eGFR < 40.9 mL/min/1.73 m2 (n = 47) had significantly lower freedom from HF hospitalization during 1-year therapeutic period (73% versus 94%, p = 0.005). Conclusions: Among patients who initiated medical therapy incorporating SGLT2i during the hospitalization for ADHF, a lower eGFR at baseline was associated with a recurrent hospitalization for HF. Early administration of SGLT2i prior to deterioration of renal function would be highly recommended to enjoy greater benefit from SGLT2i.

Initial Real-World Practical Experience of Sacubitril/Valsartan Treatment in Japanese Patients With Chronic Heart Failure.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has demonstrated survival benefit and reduces heart failure hospitalization compared with enalapril in patients with heart failure and reduced ejection fraction. However, its efficacy in real-world practice in Japan remains unknown. Methods and Results: We initiated sacubitril/valsartan treatment for 37 patients (median age 68 years; median left ventricular ejection fraction 37%) between August and November 2020. Within 3 months, sacubitril/valsartan was discontinued in 3 patients due to symptomatic hypotension or worsening heart failure. Two patients were hospitalized due to worsening heart failure, with one of these patients undergoing percutaneous mitral valve repair. Three patients received scheduled non-pharmacological treatment: 1 received cardiac resynchronization therapy (CRT), 1 received CRT and underwent transcatheter aortic valve implantation, and 1 underwent left ventricular assist device implantation. Of the 30 patients who continued sacubitril/valsartan for 3-6 months without additional non-pharmacological therapy, there was a tendency for a decrease in N-terminal pro B-type natriuretic peptide concentrations (baseline vs. after 3-6 months ARNI treatment; median 733 vs. 596 pg/mL; P=0.097) and an increase in left ventricular ejection fraction (median 37% vs. 39%; P=0097). Conclusions: Sacubitril/valsartan therapy with a lower initial dose was safe and may be effective in Japanese heart failure patients in a real-world setting. Further evaluation of optimal patient selection and clinical management using sacubitril/valsartan is warranted.