Optimal Timing of Serial 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography after Prednisolone Treatment Introduction for Cardiac Sarcoidosis.

Immunosuppressive therapy with prednisolone (PSL) is the first-line treatment for cardiac sarcoidosis (CS), and 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is used to evaluate its efficacy to guide treatment. However, the appropriate timing of FDG-PET in CS remains unknown. This single-center, retrospective, observational study included 15 consecutive CS patients who underwent 3 serial FDG-PET scans (at baseline, in the early phase [1-2 months after PSL introduction], and in the late phase [≥ 5 months after PSL introduction with a maintenance dose of PSL]). We adhered to the PSL tapering protocol by the Japanese Circulation Society even when early FDG-PET showed positive results (SUVmax ≥ 4.0). No patient died during the 908 (644-1600) days of observation. Negative results in the late phase were observed in 3 of 6 early-positive patients, and 3 of 9 early-negative patients showed positive results in the late phase. Changes in echocardiographic parameters from baseline to the late phase were significantly better in late-negative patients than in late-positive patients (left ventricular end-diastolic diameter: -0.7 (-9.3-[-0.5]) mm versus +3.5 (0.8-7.5) mm, P = 0.039; left ventricular end-systolic diameter: -4.2 (-6.9-[-0.1]) mm versus +5.1 (0.5-7.0) mm, P = 0.015; left ventricular ejection fraction: +4.7% (-1.0-9.0%) versus -1.5% (-11.3-1.5%), P = 0.045) ), although early FDG-PET did not predict those consequent changes. An interval of ≥ 5 months after introducing the PSL with a maintenance dose of PSL is long enough for FDG-PET to reflect consequent left ventricular functions, while an interval of 1-2 months can be too short.

Paradigm shift in heart failure treatment: are cardiologists ready to use gliflozins?

Despite recent advances in chronic heart failure (HF) therapy, the prognosis of HF patients remains poor, with high rates of HF rehospitalizations and death in the early months after discharge. This emphasizes the need for incorporating novel HF drugs, beyond the current approach (that of modulating the neurohumoral response). Recently, new antidiabetic oral medications (sodium-glucose cotransporter 2 inhibitors (SGLT2i)) have been shown to improve prognosis in diabetic patients with previous cardiovascular (CV) events or high CV risk profile. Data from DAPA-HF study showed that dapaglifozin is associated with a significant reduction in mortality and HF hospitalization as compared with placebo regardless of diabetes status. Recently, results from EMPEROR-Reduced HF trial were consistent with DAPA-HF trial findings, showing significant beneficial effect associated with empagliflozin use in a high-risk HF population with markedly reduced ejection fraction. Results from the HF with preserved ejection fraction trials using these same agents are eagerly awaited. This review summarizes the evidence for the use of gliflozins in HF treatment.

One-Year Prognosis of Kidney Injury at Discharge From the ICU: A Multicenter Observational Study.

OBJECTIVES: The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge. DESIGN: Ancillary investigation of a prospective observational study. SETTING: Twenty-one ICUs with 1-year follow-up. PATIENTS: Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included. INTERVENTIONS: Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors. MEASUREMENTS AND MAIN RESULTS: The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25-47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease). CONCLUSIONS: Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.

Effects of tolvaptan on urine output in hospitalized heart failure patients with hypoalbuminemia or proteinuria.

Hypoalbuminemia is an independent prognostic factor in hospitalization for heart failure (HHF). Hypoalbuminemia or proteinuria is related to resistance to loop diuretics. Tolvaptan is an oral non-peptide, competitive antagonist of vasopressin receptor-2. It has been used for the treatment of volume overload in HHF patients in several Asian countries. Several studies have demonstrated marked improvement in congestion in HHF patients. However, whether tolvaptan is useful for HHF patients with hypoalbuminemia or proteinuria (both of which are related to resistance to loop diuretics) has not been clarified. We examined the diuretic response to tolvaptan in HHF patients with hypoalbuminemia or proteinuria. We defined hypoalbuminemia as a serum level of albumin < 2.6 g/dl. Fifty-one HHF patients who received additional tolvaptan upon therapies with loop diuretics were divided into the hypoalbuminemia group (n = 24) or control group (n = 27). The changes in urine output per day were not different between the two groups [610 (range 100-1032); 742 (505-1247) ml, P = 0.313]. There was no difference in diuretic responses between patients with and without proteinuria. The serum level of albumin did not correlate with changes in urine output per day after tolvaptan treatment (P = 0.276, r = 0.156). Thus, additional administration of tolvaptan elicited a good diuretic response in HHF patients with hypoalbuminemia or proteinuria. These data suggest that tolvaptan might be beneficial for such HHF patients.

Post-translational modifications enhance NT-proBNP and BNP production in acute decompensated heart failure.

BACKGROUND: Increases in plasma B-type natriuretic peptide (BNP) concentrations in those with acutely decompensated heart failure (ADHF) has been mainly attributed to an increase in NPPB gene transcription. Recently, proBNP glycosylation has emerged as a potential regulatory mechanism in the production of amino-terminal (NT)-proBNP and BNP. The aim of the present study was to investigate proBNP glycosylation, and corin and furin activities in ADHF patients. METHODS AND RESULTS: Plasma levels of proBNP, NT-proBNP, BNP, as well as corin and furin concentration and activity were measured in a large cohort of 683 patients presenting with ADHF (n = 468), non-cardiac dyspnoea (non-ADHF: n = 169) and 46 patients with stable chronic heart failure (CHF); the degree of plasma proBNP glycosylation was assessed in a subset of these patients (ADHF: n = 49, non-ADHF: n = 50, CHF: n = 46). Our results showed a decrease in proBNP glycosylation in ADHF patients that paralleled NT-proBNP overproduction (ρ = -0.62, P < 0.001) but less so to BNP. In addition, we observed an increase in furin activity that is positively related to the plasma levels of proBNP, NT-proBNP and BNP overproduction (all P < 0.001, all ρ > 0.88), and negatively related to the degree of proBNP glycosylation (ρ = -0.62, P < 0.001). CONCLUSION: These comprehensive results provide a paradigm for the post-translational modification of natriuretic peptides in ADHF: as proBNP glycosylation decreases, furin activity increases. This synergistically amplifies the processing of proBNP into BNP and NT-proBNP. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/. Identifier: NCT01374880.

Frailty, Sarcopenia, Cachexia, and Malnutrition in Heart Failure.

With global aging, the number of patients with heart failure has increased markedly. Heart failure is a complex condition intricately associated with aging, organ damage, frailty, and cognitive decline, resulting in a poor prognosis. The relationship among frailty, sarcopenia, cachexia, malnutrition, and heart failure has recently received considerable attention. Although these conditions are distinct, they often exhibit a remarkably close relationship. Overlapping diagnostic criteria have been observed in the recently proposed guidelines and position statements, suggesting that several of these conditions may coexist in patients with heart failure. Therefore, a comprehensive understanding of these conditions is essential, and interventions must not only target these conditions individually, but also provide comprehensive management strategies. This review article provides an overview of the epidemiology, diagnostic methods, overlap, and prognosis of frailty, sarcopenia, cachexia, and malnutrition in patients with heart failure, incorporating insights from the FRAGILE-HF study data. Additionally, based on existing literature, this article discusses the impact of these conditions on the effectiveness of guideline-directed medical therapy for patients with heart failure. While recognizing these conditions early and promptly implementing interventions may be advantageous, further data, particularly from well-powered, large-scale, randomized controlled trials, are necessary to refine personalized treatment strategies for patients with heart failure.

Early-pregnancy N-terminal pro-brain natriuretic peptide level is inversely associated with hypertensive disorders of pregnancy diagnosed after 35 weeks of gestation.

Hypertensive disorders of pregnancy (HDP) are among the major causes of high maternal and fetal/neonatal morbidity and mortality rates. Patients with HDP have significantly elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at diagnosis; however, the NT-proBNP levels during early pregnancy are largely unknown. This study aimed to validate the association between HDP and NT-proBNP levels. This retrospective study evaluated 103 pregnant women who developed HDP diagnosed after 35 weeks of gestation and 667 who did not. The HDP group had significantly lower early-pregnancy NT-proBNP levels than the without HDP group. However, the two groups did not significantly differ in terms of the late-pregnancy NT-proBNP levels. After adjusting for confounding factors such as age, body mass index, parity, and blood pressure levels, high early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Early-pregnancy NT-proBNP levels ≥ 60.5 pg/mL had a negative predictive value of 97.0% for ruling out HDP, with a sensitivity of 87.4% and specificity of 62.5%. In conclusion, elevated early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Moreover, a cutoff point of ≥ 60.5 pg/mL for early-pregnancy NT-proBNP levels had a high negative predictive value and sensitivity for ruling out HDP. These findings can provide new clinical implications.

Atrial fibrillatory wave amplitude revisited: A predictor of recurrence after catheter ablation independent of the degree of left atrial structural remodeling.

BACKGROUND: The fibrillatory wave amplitude (FWA) during atrial fibrillation (AF) is thought to reflect structural atrial remodeling, but it remains unclear what determines the FWA. METHODS: 114 consecutive patients were prospectively studied who underwent catheter ablation of AF. The mean FWA was computed by automated surface ECG analyses. The extent of the left atrial (LA) voltage-defined atrial fibrosis and conduction properties were estimated by a three-dimensional high-density electroanatomical mapping system. The LA size was evaluated by transthoracic echocardiography. The study patients were divided into 2 groups according to an FWA in lead V1 above the median value of 46 µV (high FWA group, n=57) or below 46 µV (low FWA group, n=57). RESULTS: There were no differences in the age, gender, CHADS2 score, prevalence of paroxysmal AF, medications, ablation strategy, and LA volume index between the two groups. The LA low voltage areas in the low FWA group were not different from those in the high FWA group. The total LA activation time and local LA conduction velocity did not differ between the two groups. During a median follow-up of 710 days, the recurrence rate after ablation was significantly higher in patients with a low FWA than a high FWA (log-rank P=0.02). In a multivariate analysis, non-paroxysmal AF, the LA volume index, and FWA were independent predictors of recurrence after　ablation. CONCLUSIONS: The FWA was not correlated with the markers of atrial structural remodeling. Nevertheless, the FWA could still provide information for predicting the clinical outcome after AF ablation.

Baseline Blood Pressure and Left Ventricular Reverse Remodeling in Dilated Cardiomyopathy with Spontaneous Mechanical Alternans.

Objective Spontaneous mechanical alternans (MA), or pulsus alternans, has been observed in heart failure patients with hypertension or tachycardia for 150 years and is considered a sign of a poor prognosis. However, in some dilated cardiomyopathy (DCM) patients with MA, optimal medical therapy (OMT) brings left ventricular reverse remodeling (LVRR), a preferable prognostic indicator. This study examined the probability of LVRR in DCM patients with spontaneous MA and whether or not LVRR can be predicted by the baseline blood pressure or heart rate. Methods We conducted a single-center, retrospective observational study of newly diagnosed DCM patients from January 2017 to December 2020. Results Thirty-three newly diagnosed DCM patients were retrospectively examined. Spontaneous MA was observed during diagnostic cardiac catheterization in at least 1 of the pressure waveforms of the aorta, left ventricle, pulmonary artery, or right ventricle in 10 patients (30%) (MA-group). LVRR after OMT was achieved roughly equally in the MA group (6 of 10, 60%) and the non-MA group (12 of 23, 52%). In the MA group, those who achieved LVRR had a significantly higher baseline systolic aortic pressure (more than 120 mmHg in all 6 patients) than those who did not, although the baseline heart rate did not show a significant correlation with LVRR. In contrast, in the non-MA group, LVRR was unrelated to the baseline aortic pressure or heart rate. Conclusion The probability of LVRR in newly-diagnosed DCM patients with spontaneous MA was similar to that in those without spontaneous MA. Spontaneous MA may not necessarily be a sign of a poor prognosis if observed in patients with a preserved blood pressure.

A case of giant cell myocarditis mimicking cardiac sarcoidosis successfully maintained by prednisolone and tacrolimus.

A 45-year-old woman with no medical history underwent pacemaker implantation for a symptomatic complete atrioventricular block. On day 6, she noticed diplopia and then fever, general malaise, and elevation of serum creatinine kinase (CK). She was transferred to our hospital on day 21. Serum CK was elevated to 4543 IU/L, and echocardiography revealed a left ventricular ejection fraction of 43 %. We diagnosed her with giant cell myocarditis (GCM) via an emergent myocardial biopsy that revealed a proliferation of lymphocytes, eosinophils, and giant cells without granulomas. Initial treatment with high doses of intravenous methylprednisolone and immunoglobulin improved her symptoms in a few days, and prednisolone was given as follow-up treatment. CK was normalized in a week and a thinning of the interventricular septum mimicking cardiac sarcoidosis (CS) occurred. On day 38, we added a calcineurin inhibitor, tacrolimus, and maintained her with a combination of prednisolone and tacrolimus at a target dose of 10-15 ng/mL. Six months after the onset, there were no signs of relapse despite the persistent mild elevation of troponin I levels. We present a case of GCM mimicking CS successfully maintained by a combination of two immunosuppressive agents. Learning objective: Recommended treatment for giant cell myocarditis (GCM), a potentially fatal disease, is a combination of three immunosuppressive agents. However, GCM shares many characteristics with cardiac sarcoidosis (CS), which is treated using prednisolone alone in many cases. Recent studies on GCM and CS suggest they are different spectrums of a common entity. Although they can clinically overlap, they have different progressive speeds and severities. We present a case of GCM mimicking CS successfully treated with a combination of two immunosuppressive agents.

Analyzing drilling noise in rotational atherectomy: Improving safety and effectiveness through visualization and anomaly detection using autoencoder-A preclinical study.

Background and Aims: As the population of aging societies continues to grow, the prevalence of complex coronary artery diseases, including calcification, is expected to increase. Rotational atherectomy (RA) is an essential technique for treating calcified lesions. This study aimed to assess the usefulness of the drilling noise produced during rotablation as a parameter for evaluating the safety and effectiveness of the procedure. Methods: A human body model mimicking calcified stenotic coronary lesions was constructed using plastic resin, and burrs of sizes 1.25 and 1.5 mm were utilized. To identify the noise source during rotablation, we activated the ROTAPRO™ rotablator at a rotational speed of 180,000 rpm, recording the noise near the burr (inside the mock model) and advancer (outside). In addition to regular operation, we simulated two major complications: burr entrapment and guidewire transection. The drilling noise recorded in Waveform Audio File Format files was converted into spectrograms for analysis and an autoencoder analyzed the image data for anomalies. Results: The drilling noise from both inside and outside the mock model was predominantly within the 3000 Hz frequency domain. During standard operation, intermittent noise within this range was observed. However, during simulated complications, there were noticeable changes: a drop to 2000 Hz during burr entrapment and a distinct squealing noise during guidewire transection. The autoencoder effectively reduced the spectrogram data into a two-dimensional representation suitable for anomaly detection in potential clinical applications. Conclusion: By analyzing drilling noise, the evaluation of procedural safety and efficacy during RA can be enhanced.

Rationale and design of the Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure: BEGIN-HF study.

AIMS: Sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) represent a unique class of anti-hyperglycaemic agents for type 2 diabetes mellitus that selectively inhibit renal glucose reabsorption, thereby increasing urinary excretion of glucose. Several studies have demonstrated the cardioprotective effects of SGLT-2i in patients with heart failure (HF), unrelated to its glucosuric effect. It is unclear whether the benefits of SGLT-2i therapy also rely on the improvement of left ventricular (LV) and/or right ventricular (RV) function in patients with HF. This study aimed to evaluate the effect of SGLT-2i on LV and RV function through conventional and advanced echocardiographic parameters with a special focus on RV function in patients with HF. METHODS AND RESULTS: The Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure (BEGIN-HF) study is an international multicentre, prospective study that will evaluate the effect of SGLT-2i on echocardiographic parameters of myocardial function in patients with chronic stable HF across the left ventricular ejection fraction (LVEF) spectrum. Patients with New York Heart Association Class II/III symptoms, estimated glomerular filtration rate > 25 mL/min/1.73 m2 , age > 18 years, and those who were not previously treated with SGLT-2i will be included. All patients will undergo conventional, tissue-derived imaging (TDI), and strain echocardiography in an ambulatory setting, at time of enrolment and after 6 months of SGLT-2i therapy. The primary endpoint is the change in LV function as assessed by conventional, TDI, and myocardial deformation speckle tracking parameters. Secondary outcomes include changes in RV and left atrial function as assessed by conventional and deformation speckle tracking echocardiography. Univariate and multivariate analyses will be performed to identify predictors associated with primary and secondary endpoints. CONCLUSIONS: The BEGIN-HF will determine whether SGLT-2i therapy improves LV and/or RV function by conventional and advanced echocardiography in patients with HF irrespective of LVEF.

Effects of intravenous nicorandil on the mid-term prognosis of patients with acute heart failure syndrome.

BACKGROUND: Acute heart failure syndrome (AHFS) remains a major clinical challenge because of its poor prognosis. Nicorandil, a hybrid compound of a potassium-channel opener and nitric oxide donor, has been reported to improve the prognosis of ischemic heart disease. We sought to evaluate the effect of intravenous nicorandil on the mid-term prognosis of AHFS. METHODS AND RESULTS: A total of 402 consecutive patients who were hospitalized for AHFS were divided into 2 groups according to the use of intravenous nicorandil: 78 patients in the Nicorandil group and 324 patients in the Control group. During the 180-day follow-up, death or rehospitalization for heart failure occurred in 7 patients in the Nicorandil group (9.0%) and in 75 patients (23.2%) in the Control group. Event-free survival rates were significantly higher in the Nicorandil group than in the Control group (P=0.006). Multivariate Cox hazard analysis revealed that age (hazard ratio (HR)=1.066, P<0.0001), systolic blood pressure (HR=0.983, P=0.0023), New York Heart Association class III/IV (HR=6.550, P<0.0001), log creatinine (HR=3.866, P=0.0106), and use of intravenous nicorandil (HR=0.179, P<0.0001) were significant predictive factors for the occurrence of death or rehospitalization for heart failure. CONCLUSIONS: Intravenous nicorandil treatment from the urgent phase of AHFS may improve the prognosis.

Last Entrainment Sequence: A Novel Diagnostic Technique for Atrial Tachycardia Mimicking Other Supraventricular Tachycardias.

BACKGROUND: Adenosine-sensitive re-entrant atrial tachycardia (AT) originating from near the atrioventricular (AV) node or AV annulus resembles other supraventricular tachycardias (SVTs), and the differential diagnosis is sometimes challenging. OBJECTIVES: This study sought to develop a novel technique to distinguish adenosine-sensitive re-entrant AT from AV nodal re-entrant tachycardia (AVNRT) and orthodromic reciprocating tachycardia (ORT). METHODS: The study retrospectively studied 117 re-entrant SVTs that were successfully entrained by atrial overdrive pacing (AOP) (27 adenosine-sensitive re-entrant ATs, 63 AVNRTs, 27 ORTs). If the second atrial electrogram after AOP (A2) at the earliest atrial activation site (EAAS) accelerated to the pacing cycle length, the EAAS was considered orthodromically activated. Then, we compared the sequence of A2 and the last entrained His bundle (H∗) and QRS complex (V∗). The study hypothesized that the last entrained impulse would activate the EAAS before it enters the AV node, His bundle, and ventricle during AT (A2-H∗-V∗) but would activate the EAAS after the His bundle activation during AVNRT and ORT (H∗-V∗-A2 or H∗-A2-V∗). RESULTS: Orthodromic EAAS activation was documented during AOP in 84 SVTs (72%) when performing AOP from sites proximal to the entrance of SVTs. A2-H∗-V∗ responses were observed in 21 of 25 ATs, but were never for AVNRTs or ORTs. All ORTs and fast-slow AVNRTs had H∗-V∗-A2 responses. Eleven of 21 slow-fast AVNRTs had H∗-A2-V∗ responses. The sensitivity, specificity, and positive and negative predictive values of the A2-H∗-V∗ response for diagnosing AT were 84%, 100%, 100%, and 94%, respectively. CONCLUSIONS: The last entrainment sequence was useful for differentiating ATs with diagnostic difficulties.

Temporal trends in mortality and readmission after acute heart failure: a systematic review and meta-regression in the past four decades.

AIMS: Acute heart failure (AHF) is frequent and life-threatening disease. However, innovative AHF therapies have remained limited, and care is based on experts' opinion. Temporal trends and benefits of long-term oral cardiovascular medications on AHF outcomes remain uncertain. METHODS AND RESULTS: This study is registered with PROSPERO (CRD42018099885). A systematic review ranging from 1980 to 2017, searched AHF studies with more than 100 patients that reported death and/or readmission. Primary outcomes were temporal trends, assessed by meta-regression, for 30-day or 1-year all-cause death and/or readmission rates. Secondary outcomes were temporal trends of oral cardiovascular therapies and their influence on primary outcomes. Among the 45 143 studies screened, 285 were included, representing 15 million AHFs. In the past decades, though mortality and readmission remain high, there was a decline in 30-day all-cause death [odds ratio (OR) for a 10-year increment: 0.74, 95% confidence interval (CI) 0.61-0.91; P = 0.004] that persisted at 1 year (OR 0.86, 95% CI 0.77-0.96; P = 0.007), while 30-day and 1-year all-cause readmission rate remained roughly unchanged. Trends of primary outcomes were linear and did not differ among continents. Decline in 1-year all-cause death rate correlated with high proportions of oral or beta-blockers, especially when combined with oral renin-angiotensin-aldosterone system inhibitors, but not with diuretics while trends in readmission remained unchanged with these therapies. CONCLUSIONS: Although AHF outcomes remain poor, the present study revealed global favourable trends of survival after AHF episodes probably associated with greater use of oral neurohormonal antagonists. The present study urges to implement the combination of oral renin-angiotensin-aldosterone system inhibitors and beta-blockers in patients at risk of AHF.

Haemodynamic effects of the nitroxyl donor cimlanod (BMS-986231) in chronic heart failure: a randomized trial.

AIMS: Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: In a randomized, multicentre, double-blind, crossover trial, 45 patients with stable HFrEF were given a 5 h intravenous infusion of cimlanod, NTG, or placebo on separate days. Echocardiograms were done at the start and end of each infusion period and read in a core laboratory. The primary endpoint was stroke volume index derived from the left ventricular outflow tract at the end of each infusion period. Stroke volume index with placebo was 30 ± 7 mL/m2 and was lower with cimlanod (29 ± 9 mL/m2 ; P = 0.03) and NTG (28 ± 8 mL/m2 ; P = 0.02). Transmitral E-wave Doppler velocity on cimlanod or NTG was lower than on placebo and, consequently, E/e' (P = 0.006) and E/A ratio (P = 0.003) were also lower. NTG had similar effects to cimlanod on these measurements. Blood pressure reduction was similar with cimlanod and NTG and greater than with placebo. CONCLUSION: In patients with chronic HFrEF, the haemodynamic effects of cimlanod and NTG are similar. The effects of cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of cimlanod will further define its potential role in the treatment of heart failure.

Differences in pharmacological property between combined therapy of the vasopressin V2-receptor antagonist tolvaptan plus furosemide and monotherapy of furosemide in patients with hospitalized heart failure.

BACKGROUND: Tolvaptan has been shown to improve congestion in heart failure patients. The purpose of this study was to evaluate the pharmacology and clinical efficacy of combined tolvaptan and furosemide therapy. METHODS: This study included 40 patients with systemic volume overload who were hospitalized for heart failure. Patients who showed no improvement in the condition after receiving 20 mg intravenous furosemide were included and were randomly selected to receive tolvaptan as an add-on to furosemide or to receive an increased dose of furosemide. We evaluated the bioelectrical impedance analyzer parameters, the parameters of the inferior vena cava using echocardiography, vital signs, body weight, urine output, and laboratory data for 5 days. RESULTS: In the changes from baseline between intracellular water volume (ICW) and extracellular water volume (ECW) after additional use of tolvaptan or furosemide from Day 1 to Day 5, there were no significant differences observed between ICW and ECW over 5 days in the tolvaptan + furosemide group, although differences were found in the furosemide group from Day 2 onward. Changes in the respiratory collapse of inferior vena cava increased significantly, and systolic blood pressure decreased significantly only in the furosemide group. CONCLUSIONS: The present study clearly demonstrates that combined therapy with tolvaptan and furosemide removed excess ICW and ECW to an equal extent, while furosemide alone primarily removed ECW, including intravascular water.

Clinical significance of arterial stiffness as a factor for hospitalization of heart failure with preserved left ventricular ejection fraction: a retrospective matched case-control study.

BACKGROUND: Previous studies have been conducted to identify characteristics of patients with heart failure with preserved ejection fraction (HFpEF), but the risk factors of HFpEF remain unclear. We investigated the associations between arterial stiffness and the risk of hospitalization for HFpEF patients. METHODS: For the case group, we enrolled patients with preserved EF who had been hospitalized for HF from April 2013 to March 2015 and examined the cardio-ankle vascular index (CAVI). For the control group, we enrolled outpatients with preserved EF and with hypertension, diabetes mellitus, dyslipidemia, and/or coronary artery disease but who did not present with HF symptoms and had never been diagnosed or treated for HF during the same period. The control group matched with the case group for age and sex. The association between hospitalized HFpEF and clinical variables was analyzed using conditional logistic regression models. RESULTS: The CAVI value was significantly higher in patients with hospitalized HFpEF compared with patients with the control [10.4 (9.8-11.0) vs. 9.2 (8.1-10.0), p < 0.001). On the multivariate conditional logistic regression analysis, high CAVI (OR 6.76, 95% CI 2.28-20.10, p < 0.001) and anemia (OR 3.91, 95% CI 1.47-10.40, p = 0.006) were independently associated with hospitalization of HFpEF patients. CONCLUSIONS: The present study has demonstrated that the high value of CAVI was independently associated with the hospitalization of HFpEF patients.

New-onset atrial fibrillation in critically ill patients and its association with mortality: A report from the FROG-ICU study.

BACKGROUND: Atrial fibrillation (AFib) is associated with adverse outcome in critical illness, but whether this effect is independent from other risk factors remains uncertain. New-onset AFib during critical illness may be independently associated with increased in-hospital and long-term risk of death. METHODS: FROG-ICU was a prospective, observational, multi-centre cohort study designed to investigate the outcome of critically ill patients. Inclusion criteria were invasive mechanical ventilation and/or treatment with a positive inotropic agent for >24 h. Heart rhythm was assessed at inclusion and during ICU stay with digital ECG recordings. Among patients who had AFib during ICU stay, new-onset and recurrent AFib were diagnosed in patients without and with previous history of AFib, respectively. Primary endpoint was in-hospital mortality; secondary endpoint was 1-year mortality among ICU survivors. RESULTS: The study included 1841 critically ill patients. During ICU stay, AFib occurred in 343 patients (19%). New-onset AFib (n = 212) had higher in-hospital mortality compared to no AFib (47 vs. 23%, P < 0.001) or recurrent AFib (34%, P = 0.032). New-onset AFib showed increased risk of in-hospital death after multivariable adjustment compared to no AFib (OR 1.6, P = 0.003) or recurrent AFib (OR 1.8, P = 0.02). Among the 1464 ICU-survivors, new-onset AFib during ICU stay showed higher post-ICU risk of death compared to no AFib (HR 2.2, P < 0.001). After multivariable adjustment, new-onset AFib showed higher post-ICU risk of death compared to no AFib (HR 1.6, P = 0.03). CONCLUSION: New-onset AFib is independently associated with in-hospital and post-ICU risk of death in critically ill patients.