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Introduction: Hyperkalemia (HK) is frequently encountered in patients treated with renin-angiotensin-aldosterone system inhibitors (RAASi), and is associated with increased mortality in heart failure (HF). While cessation of RAASi is considered an option in HK patients, the serum potassium (sK) threshold for RAASi cessation in HF patients remains unclear . Herein, we sought to assess the impact of RAASi cessation or continuation on risk-benefit balance of hyperkalemic HF patients using propensity score (PS)-matched and cubic spline regression analysis in a nationwide administrative database. Methods: An observational retrospective study was conducted using Japanese hospital claims dataset (April 2008-September 2018). HK was defined as at least two sK ≥5.1 mmol/L within 12-months interval. We examined HK patients on RAASi in HF by employing PS matching to compare risk-benefit between patients with or without RAASi cessation. Cubic spline regression was fit to calculated hazard ratios (HR) in each sK strata for this assessment. Results: Out of 1,208,894 patients, 5,059 HF with HK patients with RAASi prescriptions met inclusion criteria (mean age 76.63 ±10.96 years). Mean follow-up period was 2.75 ± 1.9 years. Cumulative incidence of RAASi cessation was 34.73% at 1 year. Cessation of RAASi was associated with incremental risk of death (+19%, P=0.009) and hospitalization (+14%, P=0.002) , whereas recurrent HK risk was decreased (-60%, P Conclusions: Our results suggest that HK management by RAASi cessation should be avoided especially in HF patients with mild to moderate HK considering the worsening risk-benefit balance.

Background: Mineralocorticoid receptor antagonist (MRA) has a potential to improve clinical outcomes in heart failure with preserved ejection fraction (HFpEF), since MRA inhibits progression of myocardial hypertrophy and fibrosis. Soluble ST2 (sST2) is a novel biomarker reflecting myocardial stress and fibrosis. MRA plays a role in the interleukin-33/ST2 signaling modulation. Hypothesis: We hypothesized that the effect of MRA on clinical outcomes in HFpEF differed by sST2 level. This study aimed to evaluate the relationship between sST2 and clinical outcomes and to test for an interaction between the effect of MRA and sST2 level. Methods: 191 patients with acute decompensated HF and EF ≥50% were prospectively enrolled. The primary endpoint was major adverse cardiovascular events (MACE), which included death from cardiovascular disease, unplanned hospitalization for heart failure, acute coronary syndrome and stroke. Results: During follow-up (421±258days), 53 patients (27.7%) met endpoints. In a multivariable analysis, use of MRA and sST2 level were significantly associated with the endpoint (HR 0.48, 95%CI 0.26-0.86, P=0.01, HR 1.02, 1.01-1.03, P=0.01). Patients were divided into 4 groups according to use of MRA and a cutoff value of sST2 (18.5 ng/ml) determined by ROC analysis. Estimated event rate for MACE were significantly higher in patients without MRA compared with those in patients with MRA regardless of category of sST2 level. In a multivariable analysis, MRA was not a significant predictor of outcome in high sST2 group (HR 0.62, 0.28-1.30, P=0.21), whereas MRA was significantly associated with improved outcome in low sST2 group (HR 0.37, 0.13-0.91, P=0.03). Conclusion: The present study showed that higher sST2 level was associated with worse prognosis and predictive of less response to MRA treatment in patients with HFpEF, which suggests that sST2 may be used to predict response to MRA treatment.

Background: We conducted a multicenter study in Japan to compare tissue Doppler echocardiography-derived and speckle tracking echocardiography (STE)-derived parameters of left ventricular (LV) diastolic function for the estimation of LV filling pressure. Methods: Seventy-eight patients (age 59±14 years, 59 male) with structural heart diseases including angina pectoris (n=34), old myocardial infarction (n=15), dilated cardiomyopathy (n=13), hypertrophic cardiomyopathy (n=8), and hypertensive heart disease (n=8) were studied according to the same protocol in 5 university hospitals in Japan. LV mean diastolic pressure (MDP) was measured by using a micromanometer-tipped catheter. Early-diastolic mitral annular velocity (e′) was measured at septal and lateral side of the annulus and averaged, and the ratio of early-diastolic transmitral velocity to e′ (E/e′) was calculated. Global longitudinal strain was measured using STE in 3 apical views and averaged on a frame-by-frame basis to construct a time-strain curve as well as a time-strain rate (SR) curve. Then, the absolute value of peak longitudinal strain (LS), early-diastolic peak SR (LSR E ), and that during isovolumic relaxation (IVR) period (LSR IVR ) were measured. Similarly, peak circumferential strain (CS), early-diastolic peak circumferential SR (CSR E ), and that during IVR (CSR IVR ) were measured from 3 short-axis views. Results: E/e′ weakly correlated with MDP (r=0.50, pIVR and E/CSR IVR did not correlate with MDP, whereas there was a significant but weak correlation between E/LSR E and MDP (r=0.50, pE and MDP (r=0.41, p Conclusions: STE-derived longitudinal parameters better correlated with MDP than circumferential parameters. Especially, E/LS was better than E/e′ for estimating LV filling pressure.

Background: Three-dimensional (3D) imaging has the potential to evaluate right ventricular (RV) function accurately because of its complex geometry. We have developed a dedicated 3D-speckle tracking imaging (STI) system for the right ventricle, and performed validation studies to assess the reliability of 3D-STI derived deformation data. Methods: In 9 anesthetized sheep, RV full volume data sets for 3D-STI were obtained using a 3D echocardiography system (Toshiba Medical Systems) simultaneously with sonomicrometry data at the baseline and during pulmonary artery (PA) banding at moderate and severe levels, and propranolol infusion. In 7 RV segments (basal and mid anterior, basal and mid lateral, basal and mid inferior, and outflow), area change ratio (ACR), longitudinal strain (LS), and circumferential strain (CS) were calculated with prototype 3D-STI software (Figures) and compared with those by sonomicrometry. Results: ACR by 3D-STI strongly correlated with sonomicrometry data (Y=0.78X-5.0, R=0.83, p Conclusions: The newly developed 3D-STI system is a reliable modality for RV function analysis.

A 21-year-old man was admitted to the hospital with exertional dyspnea. At the age of 14, he was diagnosed with Danon disease by genetic analysis (a 2–base-pair deletion at positions 288 and 289 in exon 3 was identified in the lysosome-associated membrane protein-2 [LAMP2] gene of the patient, which led to a frameshift and resulted in a premature stop codon). A chest radiograph demonstrated moderate cardiomegaly (cardiothoracic ratio of 58%). The ECG exhibited normal sinus rhythm, wide and bifid P waves with a duration of 170 ms, complete left bundle-branch block with a QRS duration of 200 ms, and a leftward axis (−2°; Figure 1). Figure 1. Twelve-lead ECGs. Echocardiography revealed left ventricular (LV) dilatation with an end-diastolic internal dimension of 60 mm and diffusely hypokinetic LV wall motion with fractional shortening of 8% (Figure 2; Movie I of the online-only Data Supplement). …

Potential myocardial dysfunction may be present in patients with significant aortic regurgitation (AR) and preserved left ventricular ejection fraction (LVEF). Newly developed software for speckle tracking imaging (STI) allows separate analysis of endo- and epimyocardial strain. The aim of this study was to assess the relationship between endo- and epimyocardial radial strain (RS) distribution and AR severity in identifying the potential myocardial dysfunction in patients with significant AR and LVEF>50%, and its correlation with postoperative LV function. We studied 47 patients with AR and 26 control subjects. Degree of AR was classified according to standard echocardiographic criteria as moderate in 16 and severe in 23 patients. STI was analyzed with the new software (Toshiba Medical Systems, Tokyo, Japan). For STI analysis, an endocardial and epicardial border line were each manually traced at end-systole on a short-axis B-mode image at the mid-ventricular level; peak RS of total, endomyocardium, and epicardium were automatically calculated. Endomyocardial RS was reduced in patients with severe AR compared to control subjects and patients with moderate AR (Figure ). Postoperative changes in LVEF were well correlated with the ratio of baseline endomyocardial RS to epimyocardial RS (n=21, r=−0.69, p

Background. Pacemaker or implantable cardiovascular-defibrillator (ICD) leads may be a primary cause of symptomatic tricuspid regurgitation (TR). The aim of this study was to evaluate the utility of 3-dimensional echocardiography (3-DE) in identifying intracardiac routes of pacemaker or ICD leads in relation to TR. Methods. 3-DE examinations were performed to evaluate intracardiac lead routes from right atrium to ventricle and positions at the tricuspid valve in 73 patients: 53 patients with pacemaker and 20 patients with ICD. TR severity was assessed by 2-dimensional echocardiography and classified as mild, moderate, or severe based on the ratio of TR area to right atrium area. Results 3-DE identified the lead route and position at the tricuspid valve in 68 patients (93.1%). In the remaining 5 patients, an appropriate image could not be obtained due to artifacts caused by the lead. TR severity was classified as mild in 47 patients, moderate in 18 patients, and severe in 8 patients. In 7 of the 8 patients with severe TR, obstruction to tricuspid valve closing caused by the lead was identified (Figure ): obstruction of septal leaflet in 3 patients, posterior leaflet in 3 patients, and anterior leaflet in 1 patient. However, in all patients with mild to moderate TR, the lead was positioned at the annulus side between leaflets, and no closing obstruction was identified. Conclusion. 3DE can identify pacemaker or ICD lead route and position at the tricuspid valve and the obstruction to closing caused by the lead in patients with severe TR. Therefore, 3DE may be useful to evaluate the cause of severe TR in patients receiving a pacemaker or ICD.