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Objective To investigate a mechanistic determinant of left atrial (LA) reservoir function in patients presenting left ventricular (LV) hypertrophy, and clarify diagnostic and prognostic values of LA reservoir strain in patients with cardiac amyloidosis (CA). Methods Three-hundred sixty patients (median age: 68 years, male gender: 65%) with left ventricular hypertrophy (LVH) assessed by echocardiography were retrospectively included. The LVH etiologies were diagnosed by any of biopsy, cardiac magnetic resonance imaging or 99mTc-PYP scintigraphy. LV segmental longitudinal strain was estimated from apical three views, and LA reservoir strain was measured from an apical 4-chamber view. Results The LVH etiologies were confirmed with CA in 81 patients, hypertensive heart disease in 87 patients, hypertrophic cardiomyopathy in 143 patients, and miscellaneous disorders in 49 patients. The median (25th, 75th percentile) value of LV ejection fraction was 59% (48–67). LV basal longitudinal strain and LA reservoir strain were significantly reduced in patients with CA compared with those with other etiologies; LV basal strain: 5.4% (3.9–8.7) vs. 11.9% (9.3–14.6), LA reservoir strain: 9.2% (6.3–12.3) vs. 17.5% (11.3–24.1), p Conclusions The decrease of LV longitudinal shortening at cardiac base could worsen LA reservoir function especially in patients with CA. LA reservoir strain might be an alternative measure to identify CA etiology and have a predictive value of heart failure hospitalization in patients with LV hypertrophy. Funding Acknowledgement Type of funding sources: None.

Background Tolvaptan (TLV), a vasopressin antagonist, can promote water diuresis and overcome various disadvantages associated with conventional diuretics by ameliorating congestive symptoms and improving hyponatremia while maintaining haemodynamics and renal function. Large-scale clinical trials conducted primarily in Western countries (e.g. EVEREST trial) failed to demonstrate the beneficial effect of TLV on prognosis in patients with heart failure (HF). However, even after these clinical trials, studies on the use of TLV add-on therapy and resultant prognosis have been reported in Asian countries. Racial differences can greatly affect drug efficacy and dosing. Purpose We sought to investigate the long-term prognostic effect of TLV add-on therapy in Asian patients with HF. Methods We searched MEDLINE, Scopus, Cochrane Central, and Google Scholar for articles published till 31 December 2019. Randomized controlled trials (RCTs) and matched case-control studies that had a follow-up period of at least 6 months and that compared TLV add-on therapy and conventional therapy (control group) in Asian patients with acute decompensated HF were included. Primary and secondary outcomes analysed were all-cause mortality and HF readmission, respectively. Pooled analysis was performed using univariate effect size with random effect models. Meta-regression was performed to assess the impact of potential covariates. Results Nine articles that enrolled 1010 patients (the range of patients in the enrolled studies: 58–217) were included in the systematic review. All studies were performed in Japan. The weighted mean follow-up period was 15 months. The weighted mean of sodium level and ejection fraction was 139 mEq/L and 47%, respectively. TLV dose at discharge was available only in five articles, and its weighted mean value was 8.8 mg/day. In the pooled analysis, TLV add-on therapy did not improve the incidence of all-cause mortality (OR: 1.02, 95% CI: 0.69–1.52, p=0.92, I2=23) and HF readmission (OR: 0.73, 95% CI: 0.24–2.22, p=0.58, I2=89) (Figure). Furthermore, the effect of TLV add-on therapy on all-cause mortality was significantly moderated by furosemide dose at discharge in the control group (p=0.03). Conclusions Similar to findings of previous RCTs completed in Western countries, we found that TLV add-on therapy did not improve long-term mortality and HF readmission in Japanese patients with HF; however, mostly small-scale studies were included in our review. TLV add-on therapy might contribute to the improvement in prognosis in HF patients taking large doses of furosemide. Forest plot of tolvaptan's effect Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Kitaishikai

Background Cardiac amyloidosis (CA), characterized by amyloid protein deposition in the heart, is a treatable disease. Although left ventricular (LV) wall thickness is the most established imaging predictor for CA, several echocardiographic indices including deformation parameters also contribute to the screening of CA. However, it is unclear whether additive values of echocardiographic indices have greater benefit over the conventional clinical predictors for the screening of CA. Therefore, we sought to compare the incremental benefits of echocardiographic indices over the clinical parameters for the screening of CA and externally validate their incremental benefits. Methods We retrospectively studied 295 consecutive patients (median age, 67 years; male, 65%; mean LV wall thickness (MWT), 12 mm) with LV hypertrophy who underwent echocardiography as well as the detailed work-up for myocardium (Biopsy, technetium pyrophosphate scintigraphy (99mTc-PYP) or cardiac magnetic resonance imaging). CA was diagnosed through biopsy or 99mTc-PYP. The clinical model considers patients' age and the low-voltage in electrocardiography in reference to previous studies. Continuous echocardiographic variables were represented in binary through generally accepted external cutoff points. The incremental benefits of the echocardiography findings over the clinical model were assessed using with the help of both receiver-operated characteristic curve analysis and comparison of area under the curves. Furthermore, these incremental benefits were validated in the external validation sample (median age, 70 years; male, 69%; MWT, 12 mm). Results Among the enrolled patients, CA was observed in 18% of cases. Table presents the results of this study. Of the echocardiographic parameters, relative apical sparing pattern (RASP) was the greatest contributor for improvement of diagnostic accuracy of the clinical model. The next greatest contributor was LV wall thickness, followed by left atrial reservoir strain (LAS), E/e', left atrial volume index, ejection fraction strain ratio, and pericardial effusion, respectively. Similarly, RASP, LV wall thickness, global longitudinal strain, ejection fraction, LAS, and granular sparkling showed significant incremental benefit in the validation cohort. Only mean wall thickness, LV wall thickness, LAS, E/e' and RASP consistently improved the diagnostic accuracy of the clinical model. Conclusion During the screening process, adding LV wall thickness, LAS, and RASP to the clinical parameters may be useful for the accurate diagnosis of CA in patients with LV hypertrophy. Figure 1 Funding Acknowledgement Type of funding source: None

Background Cardiac amyloidosis (CA) is an infiltrative disease mimicking left ventricular hypertrophy (LVH), although its prognosis is poorer than other diseases with LVH. Moreover, because CA is treatable, appropriate screening for CA is an important area of study for clinicians to prevent and treat the disease. Several imaging predictors of CA have been reported so far;. in particular, deformation parameters such as relative apical sparing patterns of longitudinal strain (RASP) may diagnose CA with better precision than conventional parameters. Accordingly, we hypothesized that the inclusion of deformation parameters into the established diagnostic parameters would permit derivation of a risk score for CA screening in patients with LVH. Thus, we aimed to 1) investigate the incremental benefits of deformation parameters over established diagnostic parameters for CA screening in patients with LVH; 2) determine the risk score to screen CA patients with LVH using all of these variables; and 3) externally validate the score. Methods We retrospectively studied 295 consecutive non-ischemic patients with LVH who underwent echocardiography as well as the detailed work-up for LVH (biopsy, technetium pyrophosphate scintigraphy (99mTc-PYP) or cardiac magnetic resonance imaging) (median age, 67 years; MWT, 12 mm). CA was diagnosed by biopsy or 99mTc-PYP. The base model consisted of age (≥65 [male], ≥70 [female]), low voltage in electrocardiography, and posterior wall thickness ≥14 mm in reference to previous studies. Continuous echocardiographic variables were binarized by the use of generally accepted external cutoff points to avoid best clinical scenario. Incremental benefits were assessed using receiver operating characteristic curve analysis and area under the curve (AUC) comparison. Multiple logistic regression analysis was performed to determine the risk score. The score was then validated in the external validation sample (N=178, median age, 70 years; MWT, 12 mm). Results CA was observed in 54 patients (18%) and of the several echocardiographic parameters studied, only RASP demonstrated a significant incremental benefit for the screening of CA over the base model (Figure A). After multiple logistic regression analysis in the prediction of CA with 4 variables (RASP and basal model components), each was assigned a numeric value based on its relative effect (Figure B). The incidence rate of CA clearly increased as the sum of the risk score increased (Figure C). The score had good discrimination ability, with an AUC of 0.87, a total score of ≥2 with 70% sensitivity and 90% specificity. Similarly, the discrimination ability of the score in the validation cohort was sufficient (AUC = 0.87). Conclusion Overall, we determined a simple risk score including RASP to screen CA. This score takes into account 4 common parameters used in daily practice, and therefore, has potential utility in risk stratification and management of patients with LVH. Figure 1 Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Kitaishikai

Background The relative apical sparing pattern (RASP) of left ventricular (LV) longitudinal strain (LS) is frequently associated with cardiac amyloidosis (CA). However, some patients with CA do not show the RASP, and their clinical characteristics have not been fully clarified. We sought to investigate the clinical significance of RASP in patients with CA. Methods One hundred consecutive CA patients who were diagnosed by biopsy or myocardial pyrophosphate scintigraphy and evaluated for RASP (mean age: 76 years, male: 77%, LV mean wall thickness: 13.5 mm, light-chain [AL] type: 33 cases, transthyretin [TTR] type: 67 cases) were retrospectively enrolled. The RASP was semi-quantitatively and quantitatively assessed. Semi-quantitative RASP was defined as reduction of LS (≥−10%) in ≥5 (of 6) basal segments relative to preserved LS (1.00, >0.90, and >0.87) according to the literature. Results Semi-quantitative and binalized quantitative RASP (>1.00, >0.90, and >0.87) were observed in 55, 55, 63, and 65 patients, respectively. RASP in each definition was more prevalent in the TTR group than in the AL group. Additionally, RASP was significantly associated with higher LV wall thickness even after adjustment for the CA subtypes (all, p Conclusions The incidence of RASP is low in the case of thin LV wall thickness in CA patients, which may indicate the difficulty of early diagnosis of CA using RASP in patients with mild LV hypertrophy. The prognostic prediction using RASP may be challenging in this cohort. Figure 1 Funding Acknowledgement Type of funding source: None