In-hospital initiation of angiotensin receptor-neprilysin inhibition in acute heart failure: the PREMIER trial.

BACKGROUND AND AIMS: The efficacy and safety of early sacubitril/valsartan (Sac/Val) initiation after acute heart failure (AHF) has not been demonstrated outside North America. The present study aimed to evaluate the effect of in-hospital Sac/Val therapy initiation after an AHF episode on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in Japanese patients. METHODS: This was an investigator-initiated, multicentre, prospective, randomized, open-label, blinded-endpoint pragmatic trial. After haemodynamic stabilization within 7 days after hospitalization, eligible inpatients were allocated to switch from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to Sac/Val (Sac/Val group) or to continue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (control group). The primary efficacy endpoint was the 8-week proportional change in geometric means of NT-proBNP levels. RESULTS: A total of 400 patients were equally randomized, and 376 (median age 75 years, 31.9% women, de novo heart failure rate 55.6%, and median left ventricular ejection fraction 37%) were analysed. The per cent changes in NT-proBNP level geometric means at Weeks 4/8 were -35%/-45% (Sac/Val group) and -18%/-32% (control group), and their group ratio (Sac/Val vs. control) was 0.80 (95% confidence interval 0.68-0.94; P = .008) at Week 4 and 0.81 (95% confidence interval 0.68-0.95; P = .012) at Week 8, respectively. In the pre-specified subgroup analyses, the effects of Sac/Val were confined to patients with a left ventricular ejection fraction < 40% and were more evident in those in sinus rhythm and taking mineralocorticoid receptor antagonists. No adverse safety signal was evident. CONCLUSIONS: In-hospital Sac/Val therapy initiation in addition to contemporary recommended therapy triggered a greater NT-proBNP level reduction in Japanese patients hospitalized for AHF. These findings may expand the evidence on Sac/Val therapy in this clinical situation outside North America. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov (NCT05164653) and Japan Registry of Clinical Trials (jRCTs021210046).

Evaluation of acute thrombus regression effect of edoxaban for deep vein thrombosis in patients with cancer: a single-center prospective observational study.

BACKGROUND: Although there are reports on the recurrence prevention in the chronic phase using direct oral anticoagulants (DOACs) for deep vein thrombosis (DVT) in patients with cancer, acute thrombus regression effect using DOACs has not been assessed. This study aimed to assess the thrombus regression effect of initial treatment using edoxaban for acute lower-extremity DVT in patients with active cancer. METHODS AND RESULTS: In this observational study, among the inpatients with cancer and lower-extremity DVT who underwent initial treatment with edoxaban at our hospital from November 2019 to December 2021, 34 consenting patients were recruited in this study. The quantitative ultrasound thrombus (QUT) score of thrombus volume was calculated at baseline (before administration) and 7-14 days after the start of edoxaban administration, using lower-extremity venous ultrasound to evaluate changes in thrombus volume. The primary and secondary endpoints were the acute thrombus regression effect of edoxaban and the impact of patients' clinical frailty on the thrombus regression effect, respectively. Anticoagulant therapy with edoxaban significantly reduced QUT score (p < 0.001). In addition, regardless of the Clinical Frailty Scale scores, QUT score decreased significantly. CONCLUSION: Initial treatment with edoxaban was effective for lower-extremity DVT in patients with cancer. In addition, the effect was the same independent of the degree of frailty.

Early initiation of tolvaptan is associated with early discharge in patients with heart failure regardless of age.

BACKGROUND: Elderly patients with heart failure (HF) have been observed to decrease activities of daily living (ADL) during hospitalization. Prevention of ADL decline from shortening of hospital stays is especially important in the elderly, because decreasing ADL is associated with poor prognosis. We investigated the relationship between the early initiation of tolvaptan (TLV) after hospitalization and the length of hospital stay in patients with HF aged younger than 80 years and aged 80 years and older. METHODS: We analyzed 146 patients younger than 80 years (< 80) and 101 patients aged 80 years and older (≥ 80) who were hospitalized with HF from February 2011 to June 2016 and had initiated TLV. The relationship between the time until commencement of TLV and the length of hospital stay was assessed. Additionally, a comparison made between the TLV early start group (within the median) and the delayed start group (over the median) for both groups. Multivariate analysis was also performed on factors that required hospital stays below the median. RESULTS: A significant correlation was observed between time to TLV initiation and the length of hospital stay (< 80: r = 0.382, P < 0.001; ≥ 80: r = 0.395, P < 0.001). The length of hospital stay in the early group was significantly longer than that in the delayed group for both groups (< 80: early 21.0 ± 13.0 days and 33.0 ± 22.7 days, respectively, P < 0.001; ≥ 80: early 21.3 ± 12.5 days and 32.9 ± 17.9 days, respectively, P < 0.001). Conversely, no statistically significant difference found in the length of hospital stay after initiation of TLV. Moreover, no increase in adverse events in the elderly observed. A multivariate analysis revealed that a predictive factor for short-term hospitalization was early administration of TLV regardless of age. CONCLUSIONS: The early initiation of TLV after hospitalization was associated with a shorter length of hospital stay in patients with HF regardless of age.

Cardio-ankle vascular index predicts the 1-year prognosis of heart failure patients categorized in clinical scenario 1.

The sudden increase in blood pressure by vascular dysfunction is associated with the development of acute decompensated heart failure (ADHF) categorized in clinical scenario (CS) 1. However, the relationship between vascular function and prognosis in ADHF patients with CS1 is unclear. 3239 consecutive ADHF patients between January 2012 and June 2018 were enrolled. ADHF patients with CS1 undergoing ankle brachial index/cardio-ankle vascular index (CAVI) were included and patients with peripheral artery disease were excluded. Finally, 113 patients were analyzed. The primary endpoint of the present study was composite endpoint at 1 year (the cardiac death or re-hospitalization by ADHF). Cox proportional hazard analysis was conducted to identify independent predictors of composite endpoint. 25 patients (22.1%) were developed composite endpoint. CAVI in patients who have composite endpoint were significantly higher than without non-composite endpoint (composite endpoint group: 9.9 ± 1.3 non-composite endpoint group 8.7 ± 1.7, P = 0.001). The composite endpoint group was elderly and had higher ejection fraction, lower hemoglobin, and less used beta blockers, and renin angiotensin aldosterone system inhibitors. After adjustment by these confounding factors, CAVI was independently associated with the occurrence of composite endpoint (hazard ratio 1.69, 95% CI 1.05-2.73, P = 0.032). A cut-off value of CAVI for predicting composite endpoint was 8.65 (sensitivity 0.444, specificity 0.920, area under the curve 0.724, 95% CI 0.614-0.834). High CAVI was associated with the occurrence of composite endpoint after CS1 ADHF.

Comparing the effects of milrinone and olprinone in patients with congestive heart failure.

Phosphodiesterase-3 (PDE3) inhibitors are widely used among patients with congestive heart failure (CHF). However, no studies have compared the cardiovascular outcomes between different PDE3 inhibitors in CHF management. In this report, we retrospectively compared the clinical benefits of two PDE3 inhibitors, milrinone and olprinone, to determine which better controls the progression of CHF. A total of 288 hospitalized patients who received PDE3 inhibitors [(milrinone; n = 77 and olprinone; n = 211, respectively)] for CHF were retrospectively enrolled. The primary endpoint was defined as having a major adverse cardiovascular and cerebrovascular event (MACCE) or cardiac death by day 60. Kaplan-Meier curves and multivariate Cox proportional models were used to compare the outcomes for patients treated with milrinone and olprinone. We found no significant differences in the baseline characteristics between the two groups. In patients treated with milrinone, a greater incidence of a MACCE or cardiac death was observed (log rank; P = 0.005 and P = 0.01, respectively). Milrinone-treated patients with ischemic heart disease and chronic kidney disease (CKD) at stage ≥ 4 presented with greater incidence of MACCE (log rank; P < 0.001 and P = 0.006, respectively). Similarly, these patients were significantly more likely to succumb to cardiac death (log rank; P < 0.001 and P = 0.02). Multivariate Cox proportional hazard models demonstrated that milrinone treatment was an independent predictor of MACCE [hazard ratio (HR) 3.17; 95% CI 1.64-6.10] and cardiac death (HR 2.64; 95% CI 1.42-4.91). Oral administration of a ß-blocker at discharge occurred more often in the olprinone-treated patients than in the milrinone-treated patients (63% vs. 29%, P = 0.004). We compared the outcomes of milrinone and olprinone treatment in patients with CHF. Those treated with milrinone were more likely to succumb to a MACCE or cardiac death within 60 days of treatment, which was especially true for patients with ischemic heart disease or CKD.

Comparable effect of tolvaptan in heart failure patients with preserved or reduced ejection fraction.

Background: It is unclear that the difference in efficacy of tolvaptan (TLV) on the length of hospital stay for both heart failure (HF) preserved ejection fraction (EF) (HFpEF) and reduced EF (HFrEF) patients.Methods: We investigated 369 patients who were hospitalized with HF from February 2011 to June 2016 and initiated TLV. Patients who died in hospital, transferred hospital or clinical scenario 4 or 5 were excluded. Finally, we analyzed 108 patients with HFpEF and 96 patients with HFrEF. We evaluated the relationship between the length of hospital stay and the date of TLV initiation. Moreover, we compared the early use (within the median) and delayed use (the median or later) of TLV.Results: The date of TLV initiation was statistically associated with the length of hospital stay in both HFpEF and HFrEF (HFpEF: r = 0.625, P < 0.001, HFrEF: r = 0.618, P < 0.001). In HFpEF, the length of hospital stay in delayed use group was significantly longer than the early use group (22.2 ± 10.7 days and 38.1 ± 22.6 days, P < 0.001). The result was similar in HFrEF (22.0 ± 15.0 days and 32.1 ± 22.0 days, P = 0.008). On the other hand, there were no statistically significant differences in the length of hospital stay after initiation of TLV in both HFpEF and HFrEF. Other findings (including the severity of HF) were similar between the early use group and the delayed group in HFpEF and HFrEF.Conclusions: The time until TLV initiation after hospitalization was related to the length of hospital stay in HFpEF and HFrEF patients.

Bisoprolol transdermal patch improves orthostatic hypotension in patients with chronic heart failure and hypertension.

ß blockers (BBs) play an important role in heart failure (HF) treatment. However, orthostatic hypotension (OH) is sometimes caused by BBs. The bisoprolol transdermal patch works more slowly and is long acting compared with the bisoprolol fumarate tablet. The risk of OH may be reduced by using the bisoprolol transdermal patch. We evaluated 57 consecutive patients who were taking the bisoprolol fumarate tablet for chronic HF with hypertension from November 2016 to September 2017. We switched the patients to the bisoprolol transdermal patch. Because 12 of 57 subjects could not continue using the bisoprolol transdermal patch, we analyzed the remaining 45 patients. We investigated BP, blood tests, and changes in BP from supine to standing positions before and after 6 months of switching from tablet to patch. OH was diagnosed by observing a systolic/diastolic BP drop of at least 20/10 mmHg or an absolute systolic BP (sBP) of <90 mmHg from the standing position. No significant changes were observed in the BP and BPs from supine to standing positions, whereas log brain natriuretic peptide was significantly reduced after switching from patch to tablet (2.102 to 2.070pg/dl, P = .039). OH, which occurred in originally 17 patients, showed improvement and eventually appeared in 4 patients. In these patients, changes in BP from supine to standing positions were also significantly improved (changes in sBP, -11 to -6mmHg, P = .016). This study demonstrated that switching from the bisoprolol fumarate tablet to transdermal patch reduced the morbidity of OH in HF patients.

The relationship between the time until commencement of tolvaptan and the length of hospital stay in heart failure patients.

The effect of early use of tolvaptan (TLV) for acute decompensated heart failure (ADHF) is unclear. We investigated the relationship between early use of TLV and the length of hospital stay. 369 consecutive ADHF patients who received TLV during hospitalization between February 2011 and June 2016 were initially enrolled. Patients who died in hospital, transferred hospital or clinical scenario 4 or 5 were excluded. We analyzed 247 ADHF patients. We evaluated the relationship between the length of hospital stay and the following findings: blood pressures, heart rate, New York Heart Association classification, and blood tests on admission. Moreover, we also evaluated treated agents and TLV initiated days from admission. TLV initiated days was statistically associated with the length of hospital stay (r = 0.625, P < 0.001). We compared the early use (within 4 days) vs delayed use of TLV (5 days or later), because the median of time until commencement of TLV from hospitalization was 4 days. The length of hospital stay in the delayed use group was significantly longer than early use group (31.9 ± 20.4 and 21.0 ± 12.9 days, P < 0.001). However, there was no difference in the length of hospital stay after initiation of TLV in both groups. Moreover, we investigated the factors related to the long-term hospitalization (hospital stay of median length or more). Multivariate analysis showed that TLV initiated days was independently related to the long-term hospitalization (odds ratio 1.32, 95% confidence interval 1.13-1.53, P < 0.001). Early use of TLV was related to the length of hospital stay for ADHF patients.

Effect of Switching from Cilnidipine to Azelnidipine on Cardiac Sympathetic Nerve Function in Patients with Heart Failure Preserved Ejection Fraction.

Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and 123I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.

Short-Term Subcutaneous Fondaparinux and Oral Edoxaban for Acute Venous Thromboembolism.

BACKGROUND: No studies have compared treatment efficacy between subcutaneous (SC) fondaparinux and oral edoxaban, which are categorized as factor Xa inhibitors, for venous thromboembolism (VTE) in the acute phase, and only a limited number of imaging-based quantitative studies have evaluated treatment.Methods and Results:In this open-label, randomized study, 50 patients with acute non-massive pulmonary embolism (PE) and/or deep-vein thrombosis (DVT) were assigned to fondaparinux or edoxaban groups. Lower-limb venous ultrasonography (US), and chest computed tomography (CT) were compared before and 7 days after treatment. Thrombus volume in DVT was calculated using quantitative ultrasound thrombosis (QUT) score on US. For evaluation of PE thrombus volume, lung perfused blood volume (PBV) on CT was calculated. The measurements before and after treatment, respectively, were as follows: QUT score: fondaparinux, 8.1±7.3 to 4.1±4.5; edoxaban, 7.7±6.3 to 4.4±4.3, both significant decreases (P=0.001, P<0.001, respectively); lung PBV: fondaparinux, 32.0±7.8 to 32.1±8.2 HU; edoxaban, 34.2±8.6 to 38.5±11.8 HU (P=0.732, P=0.426, respectively). On subjective CT-based evaluation, all pulmonary artery-related filling defects decreased/disappeared after treatment in both groups (P=NS). CONCLUSIONS: Both SC fondaparinux and oral edoxaban are effective in acute VTE. Effects on thrombus regression on imaging-based quantitative measurement did not differ between the 2 drugs.

Serum angiotensin-converting enzyme 2 concentration and angiotensin-(1-7) concentration in patients with acute heart failure patients requiring emergency hospitalization.

The existence of a new cascade, angiotensin-converting enzyme (ACE) 2/angiotensin (Ang)-(1-7)/Mas receptor axis, has been recently established in the renin-angiotensin system. However, the dynamics of this cascade under various pathological conditions in clinical settings is still unclear. Forty-nine patients who underwent emergency hospitalization because of acute heart failure (AHF) consented to participate in this study. Thirty-eight healthy volunteers served as controls. Serum ACE activity, ACE2, Ang-(1-7) concentration, plasma Ang II, aldosterone concentration, and plasma renin activity (PRA) were measured at the acute stage. We conducted a comparative study between patients with AHF and healthy volunteers. Patients with AHF showed lower serum ACE activity and plasma aldosterone concentration than healthy volunteers (12.3 vs. 15.1 IU/L, respectively; P = 0.01, 75.6 vs. 125.3 pg/mL, respectively; P = 0.000); there were no differences between the two groups in PRA and plasma Ang II concentration. Patients with AHF had a higher serum ACE2 concentration than healthy volunteers (7.9 vs. 4.8 ng/mL, respectively; P = 0.002), but their serum Ang-(1-7) concentration was significantly lower (2.4 vs 3.1 ng/mL, respectively; P = 0.005). Patients with AHF had a higher serum ACE2 concentration, lower serum Ang-(1-7) concentration, and lower serum ACE activity and plasma aldosterone concentrations than healthy volunteers, whereas PRA and plasma Ang II concentration were the same.

Azelnidipine is a useful medication for the treatment of heart failure preserved ejection fraction.

BACKGROUND: The optimal therapy in patients with heart failure preserved ejection fraction (HFpEF) and hypertension (HT) has not been revealed. The beta blocker (BB) and the renin angiotensin aldosterone system inhibitor (RAAS-I) are recommend as class IIa in patients with HFpEF. The calcium channel blocker (CCB), a major anti-hypertensive drugs in Japan, is also recommend as class IIa in patients with HFpEF. However, the difference between azelnidipine, an L type CCB, and cilnidipine, an N type CCB, is unclear. We investigated the difference between azelnidipine and cilnidipine in patients with HFpEF and HT. METHODS: Twenty-five consecutive HFpEF patients treated with BB and RAAS-I from April 2013 to March 2015 were enrolled. Initially, cilnidipine was used, and then switched to azelnidipine. Age, gender, blood pressure (BP), heart rate (HR), blood tests, echocardiography, and cardiac-scintigraphy (123I-metaiodobenzylguanidine: MIBG) were measured before and after six months from azelnidipine administration. RESULTS: There was no statistically significant difference in BP. B type natriuretic peptides were significantly reduced (pre-state: 195.4 ± 209.7 pg/ml and post-state: 140.7 ± 136.4 pg/ml, p = 0.050). In echocardiography, the TEI index tended to be decreased (pre-state: 0.47 ± 0.15 and post-state: 0.42 ± 0.08, p = 0.057). As for MIBG, there was no significant change in the heart/mediastinum ratio. However, the washout rate was significantly reduced (pre-state: 44.7 ± 12.2 and post-state: 40.7 ± 12.1, p = 0.011). In addition, there was no statistically significant change, although HR tended to decrease by switching to azelnidipine (pre-state: 62.7 ± 11.6 and post-state: 61.8 ± 16.5, p = 0.373). CONCLUSIONS: In patients with HT and HFpEF, azelnidipine improved the severity of HF and cardiac sympathetic nerve activity compared with cilnidipine.

Efficacy of Dabigatran for Dissolving Deep Vein Thromboses in Outpatients With a Deteriorated General Condition.

Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used for the prevention of ischemic strokes in patients with nonvalvular atrial fibrillation (AF). At present, NOACs have been evaluated for the treatment of deep vein thrombosis (DVT). We examined the efficacy of dabigatran, the first NOAC for anticoagulation of AF in Japan, in outpatients who suffered from DVTs under a deteriorated general condition.Thirty-six consecutive outpatients diagnosed with DVT at our institute were enrolled. Not all patients could be hospitalized due to other clinical problems; 15 (42%) had malignant tumors, 9 (25%) psychological disorders, and 6 (17%) postoperative orthopedic disease. Dabigatran was administered at a dose of 110-150 mg once or twice daily, depending on the renal function and age. The mean dosage of dabigatran was 211.7 ± 36.6 mg per day. In 18 (50%) patients, the DVTs were completely dissolved and disappeared over a treatment term of 4.3 ± 4.3 months. In 9 patients (25%), the DVTs partly dissolved, but in the remaining 9 (25%) patients, dabigatran was totally ineffective. During a follow-up of 30.5 ± 5.3 months, DVTs did not recur with dabigatran in 18 patients with an effective efficacy. In a multivariate analysis, patients with small sized thromboses and those without malignant tumors were significantly associated with the DVTs dissolving (P = 0.003 and P = 0.006, respectively).Dabigatran was effective for dissolving DVTs in outpatients with a poor condition, particularly when the size of the DVT was small and malignant tumors were absent.

Right Bundle Branch Block and Rehospitalization in Patients With Heart Failure.

OBJECTIVE: The most important aspect of managing heart failure (HF) is preventing rehospitalization. Bundle branch block (BBB), particularly left BBB (LBBB), has been a known risk factor for worsening prognosis, whereas no such consideration has been made for right BBB (RBBB). However, recent research has shown that RBBB was associated with increased mortality. This study evaluated the effects of RBBB on prognosis, especially rehospitalization, in patients with HF. MATERIALS: This study included 698 patients admitted for HF. Those who died in the hospital (n = 31) and dropped out during observation (n = 143) were excluded. After one year of observation, the patients were divided into a control group (n = 361) and a major adverse cardiovascular event (MACE) group (n = 163). After further excluding according to electrocardiography findings, patients were categorized as having no BBB (n = 307), pure RBBB (n = 37), and LBBB (n = 56), and then the characteristics, clinical data, and prognosis of the remaining patients were evaluated. RESULTS: Patients were compared to no BBB, pure RBBB, and LBBB was associated with a risk for HF rehospitalization (p = 0.007). Furthermore, pure RBBB was independently associated with HF rehospitalization even after adjusting for confounders (hazard ratio: 2.40 (95% confidence interval: 1.26-4.58; p = 0.008). CONCLUSION: Pure RBBB was independently associated with HF rehospitalization, highlighting the need for vigilance against the risk of HF rehospitalization among those with pure RBBB.

Role of Vascular Function in the Prognosis of Heart Failure Patients.

Background: Blood vessels have the Windkessel effect and are involved in blood circulation. The breakdown of this mechanism is also involved in the pathogenesis of heart failure (HF); however, the relationship between vascular dysfunction and HF prognosis is not fully understood. Methods: We evaluated 214 patients hospitalized for HF at our institution who underwent a cardio-ankle vascular index (CAVI), which evaluates vascular function, between January 2012 and July 2018. To investigate factors (including CAVI) associated with major adverse cardiac events (MACE) during 1 year after patients with HF were discharged, we evaluated clinical profiles, blood tests, chest X-P, 12-lead electrocardiography, and transthoracic echocardiographic findings. MACE was defined as cardiovascular death or readmission for HF. Results: The severity of HF between the MACE and non-MACE was not significantly different. Previous HF and chronic kidney disease were significantly more common in the MACE group. CAVI and % mean atrial pressure in the MACE group were statistically higher than those in the non-MACE group. The cardiac shadow as shown by chest X-P and left ventricular size in the MACE group were significantly bigger, and HF preserved ejection fraction (EF) (EF > 50%) was significantly more common in the MACE group. In multivariate analysis, CAVI was an independent predictive factor for the occurrence of MACE (model 1; hazard ratio (HR): 1.33, 95% confidence interval (CI): 1.05-1.68, p = 0.018; model 2; HR: 1.31, 95% CI: 1.07-1.60, p = 0.009). Conclusions: Because high CAVI is associated with poor prognosis of HF, these patients require more careful treatment.

A Case of Non-Tachycardic Atrial Fibrillation Whose Left Ventricular Systolic Dysfunction Improved After Catheter Ablation.

It is difficult to identify the causes and optimal treatment of heart failure (HF) in patients with atrial fibrillation (AF) and HF with reduced ejection fraction (EF) (HFrEF). Tachyarrhythmia can cause left ventricular (LV) systolic dysfunction called tachycardia-induced cardiomyopathy (TIC). In patients with TIC, conversion to sinus rhythm may lead to improvement in LV systolic dysfunction. However, it is unclear whether we should try to convert patients with AF without tachycardia to sinus rhythm. A 46-year-old man with chronic AF and HFrEF came to our hospital. His New York Heart Association (NYHA) classification was class II. The blood test showed a brain natriuretic peptide of 105 pg/mL. Electrocardiogram (ECG) and 24-h ECG showed AF without tachycardia. Transthoracic echocardiography (TTE) showed left atrial (LA) dilatation, LV dilatation, and diffuse LV hypokinesis (EF was 40%). Although he was optimized medically, NYHA classification II persisted. Therefore, he underwent direct current cardioversion and catheter ablation. After his AF converted to a sinus rhythm of heart rate (HR) 60 - 70 beats per minute (bpm), TTE showed improvement in LV systolic dysfunction. We gradually reduced oral medications for arrhythmia and HF. We subsequently succeeded in discontinuing all medications 1 year after catheter ablation. TTE performed between 1 and 2 years after catheter ablation showed normal LV function and normal cardiac size. During the 3 years of follow-up, there was no recurrence of AF, and he was not readmitted to the hospital. This patient showed the effectiveness of converting AF to sinus rhythm in patients without tachycardia.

Cardiac Amyloidosis Patient With Cardiac Conduction Disturbances.

Transthyretin cardiac amyloidosis (ATTR-CA) has recently been diagnosed more because of advances in diagnostic techniques, such as 99mTc-labeled pyrophosphate (99mTc-PYP) scintigraphy. ATTR-CA remains poorly diagnosed by many physicians, except for cardiologists and neurologists, and by patients. In this manuscript, we present a patient who was recommended to undergo a close examination but developed cardiac conduction disturbances and defects due to delays in the examination and treatment initiation. The patient was a 72-year-old Japanese man treated for hypertension at our hospital for approximately 30 years. The patient was diagnosed with left ventricular hypertrophy at 62 years old and hospitalized for heart failure at 68 years old. ATTR-CA was suspected by 99mTc-PYP scintigraphy performed at 70 years old, and a skin biopsy was performed. However, the skin biopsy did not confirm the diagnosis, and myocardial biopsy was recommended, which was declined by the patient. He finally consented to myocardial biopsy 2 years later, leading to the diagnosis of ATTR-CA at 72 years old. However, the patient had atrial fibrillation and a complete atrioventricular block. If ATTR-CA were widely recognized and understood, it might have been diagnosed and treated before the cardiac conduction disturbances appeared. It is essential to have an understanding and appropriate examinations for ATTR-CA based on sufficient explanation and consent.

Importance of anemia in heart failure over blood pressure variability.

BACKGROUND: The evaluation of arteriosclerosis (vascular function) is important when treating heart failure (HF). Vascular dysfunction is associated with anemia through renal function and endothelial nitric oxide synthase. Additionally, blood pressure (BP) variability (BPV) caused by vascular dysfunction is also associated with HF prognosis. However, how anemia and BPV may affect HF prognosis is unclear. METHODS: Between January 2012 and July 2018, 214 patients with HF were hospitalized. The cardio-ankle vascular index (CAVI) as an index of arteriosclerosis of these patients was measured. The patients were divided into the elevated and preserved CAVI groups. We investigated the factors related to major adverse cardiovascular events (MACEs) as cardiovascular death or rehospitalization within 1 year after discharge. RESULTS: In the elevated CAVI group, significant differences in body mass index (BMI), BPV, left ventricular dimension, and hemoglobin levels were observed between patients with and without MACEs. In the preserved CAVI group, significant differences in BMI, diastolic/mean BP, and hemoglobin levels were observed between those with and without MACEs. The multivariate analysis showed an independent association between hemoglobin levels and MACE occurrence in both the elevated and preserved CAVI groups (elevated CAVI group: hazard ratio [HR] = 0.800, p = .045 [model 1], HR = 0.802, p = .035 [model 2]; preserved CAVI group: HR = 0.783, p = .049 [model 1], HR = 0.752, p = .023 [model 2], and HR = 0.754, p = .024 [model 3]). CONCLUSIONS: Anemia was independently associated with HF prognosis with or without arteriosclerosis.

Effectiveness of Fondaparinux in the Japanese Population with Acute Venous Thromboembolism -A Study Comparing Patients with and without Cancer.

Objective Venous thromboembolism (VTE) is a common cancer complication. Patients with cancer have a high risk of recurrent VTE and bleeding. We analyzed the effectiveness of VTE treatment via subcutaneous fondaparinux injection for patients with and without cancer. Methods This study included 260 inpatients who had received fondaparinux therapy. Fondaparinux's therapeutic effect was quantitatively and qualitatively evaluated by imaging tests. To quantitatively evaluate the deep vein thrombosis (DVT) clot burden of the lower limbs, we calculated the quantitative ultrasound thrombosis (QUT) score, which was devised by our institution. Results There were 80 and 180 patients with and without cancer, respectively. The QUT score significantly reduced after treatment in both groups (cancer: 6.70±4.37 vs. 4.19±4.17, p<0.001; noncancer: 7.08±4.37 vs. 4.17±3.94, p<0.001). The changes in the QUT score showed no significant difference between the 2 groups (cancer: 2.23±3.09; noncancer: 3.04±3.45, p=0.06). In addition, the quantitative evaluation of pulmonary thromboembolism (PTE) after treatment showed that PTE decreased or disappeared in 38/40 patients (95.0%) in the cancer group and 55/63 patients (87.3%) in the noncancer group, indicating no significant difference in the improvement rate between the groups. Conclusion Fondaparinux was effective for VTE both in patients with and without cancer, with no significant differences in the changes in the QUT score. However, the change in the QUT score was smaller in patients with cancer than in those without cancer, suggesting that the efficacy of fondaparinux might be diminished in patients with cancer.

Rationale and Design of the Effect of Ivabradine on Exercise Tolerance in Patients With Chronic Heart Failure (EXCILE-HF) Trial　- Protocol for a Multicenter Randomized Controlled Trial.

Background: A high resting heart rate is an independent risk factor for mortality and morbidity in patients with cardiovascular diseases. Ivabradine selectively inhibits the funny current (I f) and decreases heart rate without affecting cardiac conduction, contractility, or blood pressure. The effect of ivabradine on exercise tolerance in patients with heart failure with reduced ejection fraction (HFrEF) on standard drug therapies remains unclear. Methods and Results: This multicenter interventional trial of patients with HFrEF and a resting heart rate ≥75 beats/min in sinus rhythm treated with standard drug therapies will consist of 2 periods: a 12-week open-label, randomized, parallel-group intervention period (standard drug treatment+ivabradine group and standard drug treatment group) to compare changes in exercise tolerance between the 2 groups; and a 12-week open-label ivabradine treatment period for all patients to evaluate the effect of adding ivabradine on exercise tolerance. The primary endpoint will be the change in peak oxygen uptake (V̇O2) during the cardiopulmonary exercise test from Week 0 (baseline) to Week 12. Secondary endpoints will be time-dependent changes in peak V̇O2 from Week 0 to Weeks 12 and 24. Adverse events will also be evaluated. Conclusions: The EXCILE-HF trial will provide meaningful information regarding the effects of ivabradine on exercise tolerance in patients with HFrEF receiving standard drug therapies and suggestions for the initiation of ivabradine treatment.