Left atrial pressure overload and prognosis in elderly patients with heart failure and preserved ejection fraction: a prospective multicenter observational study. Hoshida Shiro,Tachibana Koichi,Shinoda Yukinori,Minamisaka Tomoko,Yamada Takahisa,Higuchi Yoshiharu,Nakagawa Yusuke,Abe Haruhiko,Fuji Hisakazu,Yasumura Yoshio,Hikoso Shungo,Nakatani Daisaku,Sakata Yasushi, , BMJ open OBJECTIVES:The severity of diastolic dysfunction is assessed using a combination of several indices of left atrial (LA) volume overload and LA pressure overload. We aimed to clarify which overload is more associated with the prognosis in patients with heart failure and preserved ejection fraction (HFpEF). SETTING:A prospective, multicenter observational registry of collaborating hospitals in Osaka, Japan. PARTICIPANTS:We enrolled hospitalised patients with HFpEF showing sinus rhythm (men, 79; women, 113). Blood tests and transthoracic echocardiography were performed before discharge. The ratio of diastolic elastance (Ed) to arterial elastance (Ea) was used as a relative index of LA pressure overload. PRIMARY OUTCOME MEASURES:All-cause mortality and admission for heart failure were evaluated at >1 year after discharge. RESULTS:In the multivariable Cox regression analysis, Ed/Ea, but not LA volume index, was significantly associated with all-cause mortality or admission for heart failure (HR 2.034, 95% CI 1.059 to 3.907, p=0.032), independent of age, sex, and the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level. In patients with a higher NT-proBNP level, the effect of higher Ed/Ea on prognosis was prominent (p=0.015). CONCLUSIONS:Ed/Ea, an index of LA pressure overload, was significantly associated with the prognosis in elderly patients with HFpEF showing sinus rhythm. TRIAL REGISTRATION NUMBER:UMIN000021831. 10.1136/bmjopen-2020-044605

Impaired left atrial function in heart failure with preserved ejection fraction. Santos Angela B S,Kraigher-Krainer Elisabeth,Gupta Deepak K,Claggett Brian,Zile Michael R,Pieske Burkert,Voors Adriaan A,Lefkowitz Marty,Bransford Toni,Shi Victor,Packer Milton,McMurray John J V,Shah Amil M,Solomon Scott D, European journal of heart failure AIMS:Left atrial (LA) enlargement is present in the majority of heart failure with preserved ejection fraction (HFpEF) patients and is a marker of risk. However, the importance of LA function in HFpEF is less well understood. METHODS AND RESULTS:The PARAMOUNT trial enrolled HFpEF patients (LVEF ≥45%, NT-proBNP >400 pg/mL). We assessed LA reservoir, conduit, and pump function using two-dimensional volume indices and speckle tracking echocardiography in 135 HFpEF patients in sinus rhythm at the time of echocardiography and 40 healthy controls of similar age and gender. Systolic LA strain was related to clinical characteristics and measures of cardiac structure and function. Compared with controls, HFpEF patients had worse LA reservoir, conduit, and pump function. The differences in systolic LA strain (controls 39.2 ± 6.6% vs. HFpEF 24.6 ± 7.3%) between groups remained significant after adjustments and even in the subsets of HFpEF patients with normal LA size or without a history of AF. Among HFpEF patients, lower systolic LA strain was associated with higher prevalence of prior HF hospitalization and history of AF, as well as worse LV systolic function, and higher LV mass and LA volume. However, NT-proBNP and E/E' were similar across the quartiles of LA function. CONCLUSIONS:In this HFpEF cohort, we observed impairment in all phases of LA function, and systolic LA strain was decreased independent of LA size or history of AF. LA dysfunction may be a marker of severity and play a pathophysiological role in HFpEF. TRIAL REGISTRATION:NCT00887588. 10.1002/ejhf.147

Left atrium decompression devices across the spectrum of ejection fraction in heart failure: an updated systematic review and meta-regression analysis. Heart failure reviews BACKGROUND:In patients affected by heart failure (HF) with reduced ejection fraction (HFrEF), pharmacological treatments have been proven to alleviate symptoms and improve prognosis, while no treatment other than sodium-glucose co-transporter-2 inhibitors have demonstrated significant effects in HF with preserved ejection fraction (HFpEF). Left atrium decompression devices (LADd) have been recently investigated as a new interventional approach in patients with HFpEF. OBJECTIVES:To assess the efficacy of LADd on soft endpoints in HF patients across the spectrum of ejection fraction. METHODS:PubMed and Web of Science were searched without restrictions from inception to 28 May 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified main outcomes were the change from baseline in 6-min walking distance (6MWD), NYHA class and health-related quality of life (HRQoL). Secondary outcomes were reduction in HF hospitalizations, echocardiographic, and hemodynamic parameters. RESULTS:Eleven studies, with a total of 547 patients, were included. LADd significantly improved 6MWD by 43.95 m (95% CI 29.64-58.26 m), decreased NYHA class by 0.93 (95% CI 1.20-0.67), and improved HRQoL questionnaire by 20.45 points (95% CI 13.77-27.14) with better results for all outcomes in patients with lower EFs. CONCLUSION:The present meta-analysis suggests that LADd are favorable in improving 6MWD, NYHA class, and HRQoL in HF across a wide spectrum of ejection fraction, with better outcomes in patients with lower EFs. TRIAL REGISTRATION:CRD42022336077, URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=336077 . 10.1007/s10741-023-10317-2

Diagnostic Accuracy of Tissue Doppler Index E/e' for Evaluating Left Ventricular Filling Pressure and Diastolic Dysfunction/Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis. Sharifov Oleg F,Schiros Chun G,Aban Inmaculada,Denney Thomas S,Gupta Himanshu Journal of the American Heart Association BACKGROUND:Tissue Doppler index E/e' is used clinically and in multidisciplinary research for estimation of left ventricular filling pressure (LVFP) and diastolic dysfunction (DD)/heart failure with preserved ejection fraction (HFpEF). Its diagnostic accuracy is not well studied. METHODS AND RESULTS:From the PubMed, Scopus, Embase, and Cochrane databases, we identified 24 studies reporting E/e' and invasive LVFP in preserved EF (≥50%). In random-effects models, E/e' had poor to mediocre linear correlation with LVFP. Summary sensitivity and specificity (with 95% CIs) for the American Society of Echocardiography-recommended E/e' cutoffs (lateral, mean, and septal, respectively) to identify elevated LVFP was estimated by using hierarchical summary receiver operating characteristic analysis. Summary sensitivity was 30% (9-48%), 37% (13-61%), and 24% (6-46%), and summary specificity was 92% (82-100%), 91% (80-99%), and 98% (92-100%). Positive likelihood ratio (LR+) was <5 for lateral and mean E/e'. LR+ was slightly >10 for septal E/e' obtained from 4 studies (cumulative sample size <220). For excluding elevated LVFP, summary sensitivity for E/e' (lateral, mean, and septal, respectively) was 64% (38-86%), 36% (3-74%), and 50% (14-81%), while summary specificity was 73% (54-89%), 83% (49-100%), and 89% (66-100%). Because of data set limitations, meaningful inference for identifying HFpEF by using E/e' could not be drawn. With the use of quality assessment tool for diagnostic accuracy studies (Quality Assessment of Diagnostic Accuracy Studies questionnaire), we found substantial risks of bias and/or applicability. CONCLUSIONS:There is insufficient evidence to support that E/e' can reliably estimate LVFP in preserved EF. The diagnostic accuracy of E/e' to identify/exclude elevated LVFP and DD/HFpEF is limited and requires further validation in a well-designed prospective clinical trial. 10.1161/JAHA.115.002530

Left atrial function in heart failure with preserved ejection fraction: a systematic review and meta-analysis. Khan Muhammad Shahzeb,Memon Muhammad Mustafa,Murad Mohammad H,Vaduganathan Muthiah,Greene Stephen J,Hall Michael,Triposkiadis Filippos,Lam Carolyn S P,Shah Amil M,Butler Javed,Shah Sanjiv J European journal of heart failure AIMS:Left atrial (LA) mechanical function may play a significant role in the development and progression of heart failure with preserved ejection fraction (HFpEF). We performed a systematic review and meta-analysis to evaluate association of impaired LA function with outcomes in HFpEF. METHODS AND RESULTS:Multiple databases were searched for original studies measuring different phases of LA function in HFpEF patients. Comparative LA function between HFpEF patients and healthy controls was assessed by pooling weighted mean differences (WMD). Adjusted hazard ratios (HRs) with 95% confidence intervals were pooled to evaluate the prognostic utility of LA function. Twenty-two studies (2 trials, 20 observational) comprising 1974 HFpEF patients and 751 healthy controls were included. HFpEF patients had decreased LA reservoir [WMD = -12.21% (-15.47, -8.95); P < 0.001], LA conduit [WMD = -5.68% (-8.56, -2.79); P < 0.001], and pump [WMD = -11.07% (-14.81, -7.34); P < 0.001] emptying fractions compared with controls. LA reservoir [WMD = -13.38% (-16.07, -10.68); P < 0.001], conduit [WMD = -4.09% (-6.77, -1.42); P = 0.003], and pump [WMD = -3.53% (-4.47, -2.59); P < 0.001] strains were also significantly lower in HFpEF patients. Decreased LA reservoir strain [HR 1.24 (1.02, 1.50); P = 0.03] was significantly associated with risk of composite all-cause mortality or heart failure hospitalization. CONCLUSIONS:Impaired LA function appears to have diagnostic and prognostic value in HFpEF, but whether indices of LA function truly refine discrimination for diagnosis or prognosis remains to be fully determined. Larger studies are needed to better evaluate associations between LA function and clinical outcomes and the role of LA function as a target for novel HFpEF therapies. 10.1002/ejhf.1643