The left atrium (LA) plays an important role in facilitating left ventricular (LV) filling by acting as a reservoir, passive conduit, and active booster pump, as well as a regulator of blood volume through A-type natriuretic peptide secretion in response to stimulation by mechanical stretch of the cavity. LA myopathy has emerged as one of the most important non-LV contributors to disease progression in heart failure with preserved ejection fraction (HFpEF). LA dysfunction is common in HFpEF and is associated with more severe pulmonary vascular disease and right ventricular dysfunction, and increases the risk of incident atrial fibrillation or atrial functional mitral regurgitation, leading to limitations in cardiac output reserve and reduced exercise capacity. LA deformation assessed by 2-dimensional speckle-tracking echocardiography is useful for estimating abnormal hemodynamics or exercise capacity, discriminating HFpEF from non-cardiac dyspnea and is an independent predictor of adverse outcome in HFpEF. Thus, interventions directly targeting LA myopathy may improve outcomes in HFpEF with LA myopathy. This review provides information regarding the physiology of the LA in patients with HFpEF and discusses the importance of evaluation of LA function, management issues, and future directions through ongoing trials of medical interventions.

Background: Carpal tunnel syndrome (CTS) is considered an early sign of cardiac amyloidosis (CA) because amyloid deposition is often confirmed in the tenosynovium removed during carpal tunnel release (CTR); however, the prevalence of concomitant CA is unclear.

Methods and Results: We prospectively examined 700 patients who underwent CTR and evaluated amyloid deposition after tenosynovium removal. Amyloid deposition was observed in 261 (37%) patients, who were significantly older and predominantly male (P<0.05). Of them, 120 agreed to cardiac screening. We performed ^{99 m}Tc-labeled pyrophosphate (^{99 m}Tc-PYP) scintigraphy in 12 patients who met either of the following criteria: (1) interventricular septal diameter (IVSd) ≥14 mm or (2) 12 mm ≤ IVSd < 14 mm with above-normal limits in high-sensitivity cardiac troponin T (hs-cTnT). Six patients (50%) had positive findings on ^{99 m}Tc-PYP scintigraphy and were diagnosed with wild-type transthyretin CA. Concomitant CA was observed in 6/120 (5%) CTR patients with amyloid deposition and 50% (6/12) in patients with left ventricular hypertrophy (≥12 mm) with increased hs-cTnT levels.

Conclusions: Amyloid deposition was frequently observed in the removed tenosynovium of elderly men with CTS. Cardiac screening may be useful for early diagnosis of CA in patients undergoing CTR with amyloid deposition.

Background: The association between the T-peak to T-end interval (Tp-e) and ventricular arrhythmia (VA) events in cardiac sarcoidosis (CS) is unknown. The purpose of this study was to investigate whether Tp-e was associated with VA events in CS patients with implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds).

Methods and Results: We retrospectively studied 50 patients (16 men; mean [±SD] age 56.3±10.5 years) with CS and ICD/CRT-D. The maximum Tp-e in the precordial leads recorded by a 12-lead electrocardiogram after ICD/CRT-D implantation was evaluated. The clinical endpoint was defined as appropriate ICD therapy. During a median follow-up period of 85.0 months, 22 patients underwent appropriate therapy and 10 patients died. Kaplan-Meier analysis revealed that the probability of the clinical endpoint was 28.3% at 2 years and 35.3% at 4 years. The optimal cut-off value of the Tp-e for the prediction of the clinical endpoint was 91 ms, with a sensitivity of 72.7% and a specificity of 87.0% (area under the curve=0.81). Multivariate Cox regression analysis showed that Tp-e ≥91 ms (hazard ratio [HR] 5.10; 95% confidence interval [CI] 1.99–13.1; P<0.001) and a histological diagnosis of CS (HR 3.84; 95% CI 1.28–11.5; P=0.016) were significantly associated with the clinical endpoint.

Conclusions: Tp-e ≥91 ms was a significant predictor of VA events in patients with CS and ICD/CRT-D.

Background: Patients with hypertrophic cardiomyopathy (HCM) show various physical findings, but their clinical significance has not been systematically evaluated.

Methods and Results: This study evaluated 105 consecutive patients with HCM who had undergone phonocardiography and external pulse recording. Physical examinations included a visible jugular a-wave (Jug-a), audible 4th sound (S4), and double or sustained apex beat. The primary outcome was a composite of all-cause death and hospitalization for cardiovascular disease. A total of 104 non-HCM subjects served as controls. The prevalence of visible Jug-a in the seated or supine position, audible S4, and a sustained or double apex beat in patients with HCM were 10%, 71%, 70%, 42%, and 27%, respectively, all of which were significantly higher than in the controls (0%, 20%, 11%, 17%, and 2%; P<0.001 for all comparisons). The combination of visible Jug-a in the supine position and audible S4 yielded a specificity of 94% and sensitivity of 57%. During a follow-up period of 6.6 years, 6 patients died and 10 were hospitalized. The absence of audible S4 was a predictor of cardiovascular events (hazard ratio, 3.91; 95% confidence interval, 1.41 to 10.8; P=0.005).

Conclusions: Detection of these findings has clinical importance in the diagnosis and risk stratification of HCM prior to the use of advanced imaging techniques.

Background: The number of patients with heart failure (HF) has increased, and it is crucial to prevent the development of HF in patients at risk of HF. The present study aimed to risk stratify patients in Stage A and B HF based on associations between exercise-induced changes in aortic stiffness and exercise tolerance.

Methods and Results: Patients in Stage A and B HF who performed a cardiopulmonary exercise test were enrolled in the study (n=106; median age 65.0 years [interquartile range 52.8–73.0 years]). Exercise tolerance was examined by the percentage of predicted peak oxygen consumption (%V̇O₂peak). The ascending aortic pressure waveform was estimated non-invasively. Aortic stiffness was assessed using the augmentation index (AIx) and reflection magnitude (RM). Multivariable regression analysis showed that AIx measured both before and after exercise was significantly associated with %V̇O₂peak (β=−0.221 [P=0.049] and β=−0.342 [P=0.003], respectively). When participants were divided into %V̇O₂peak subgroups using a cut-off value of 60%, RM decreased immediately after exercise and remained lower 5 min after exercise in the group with preserved exercise tolerance, but recovered to baseline levels 5 min after exercise in the group with reduced exercise tolerance.

Conclusions: Exercise-induced increases in aortic stiffness were associated with exercise tolerance in patients at risk of HF, suggesting that exercise-induced changes in aortic stiffness may be useful to stratify high-risk patients.

Background: Patients with atrial fibrillation (AF) and heart failure (HF) have elevated left ventricular end-diastolic pressure in addition to decreased left atrial (LA) function, but there are few reports of useful prognostic indices that can be seen on echocardiography. In this study, we investigated the association between LA reservoir strain (LARS) and prognosis in this group of patients.

Methods and Results: We retrospectively enrolled patients with acute HF complicated by AF who were consecutively admitted to hospital between January 2014 and December 2018. A total of 320 patients (mean age 79±12 years, 163 women) were included in the analysis. During a median follow-up of 473 days, 92 cardiovascular deaths and 113 all-cause deaths occurred. In the multivariate analysis, LARS was an independent predictor of all-cause death (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90–0.99, P=0.016). Multivariate analysis also showed that the patients in the lowest LARS tertile (<7.16%) had a significantly increased risk of cardiovascular death (HR 1.76, 95% CI 1.05–2.96; P=0.033) and all-cause death (HR 1.90, 95% CI 1.17–3.08; P=0.009) in comparison with patients in the highest LARS tertile (>10.52%).

Conclusions: We found a significant association between LARS and death in patients with AF and HF. Patients with reduced LARS had poor prognosis, suggesting the need for aggressive therapy to improve their LA dysfunction.

Background: This study used echocardiography to investigate non-invasive myocardial work (MCW) indices in infants born to mothers with diabetes mellitus (DM) in pregnancy (gestational DM: GDM), including those diagnosed under novel classification criteria and those with pre-existing DM.

Methods and Results: This single-centered, retrospective study included 25 infants born to mothers with GDM (termed “infant with GDM”), which was diagnosed by oral glucose tolerance test results during pregnancy or the presence of diabetes before the current pregnancy. We evaluated the relationship between the infant’s MCW, such as global constructive work (GCW), global work index (GWI), global work efficiency (GWE), and global wasted work (GWW), and the mother’s GDM maximal HbA1c during pregnancy. HbA1c level in GDM significantly negatively correlated with GWI* (r=−0.565) and GCW* (r=−0.641). In infants with GDM, GWI and GCW were significantly higher with <6.5% HbA1c than in those with >6.5% HbA1c GDM; however, the specific-layer global longitudinal strain analyses did not show any significant differences between the groups. The pressure-strain loop in infants with >6.5% HbA1c in GDM tended to be smaller than in those infants with <6.5% HbA1c GDM.

Conclusions: The hyperglycemic environment of GDM leads to impaired MCW in the infants. MCW is useful for screening for cardiac illnesses among infants with GDM. Appropriate maternal blood glucose management while maintaining HbA1c <6.5% might be beneficial for the cardiac performance of infants with GDM.

Background: Recently, destination therapy (DT) was approved in Japan, and patients ineligible for heart transplantation may now receive durable left ventricular assist devices (LVADs). Several conventional risk scores are available, but a risk score that is best to select optimal candidates for DT in the Japanese population remains unestablished.

Methods and Results: A total of 1,287 patients who underwent durable LVAD implantation and were listed for the Japanese registry for Mechanically Assisted Circulatory Support (J-MACS) were eligible for inclusion. Finally, 494 patients were assigned to the derivation cohort and 487 patients were assigned to the validation cohort. According to the time-to-event analyses, J-MACS risk scores were newly constructed to predict 3-year mortality rate, consisting of age, history of cardiac surgery, serum creatinine level, and central venous pressure to pulmonary artery wedge pressure ratio >0.71. The J-MACS risk score had the highest predictability of 3-year death compared with other conventional scores in the validation cohort, including HeartMate II risk score and HeartMate 3 risk score.

Conclusions: We constructed the J-MACS risk score to estimate 3-year mortality rate after durable LVAD implantation using large-scale multicenter Japanese data. The clinical utility of this scoring to guide the indication of DT should be validated in the next study.

Background: We investigated the components of frailty associated with hospitalization-associated disability (HAD) after cardiac surgery.

Methods and Results: This retrospective, observational study evaluated 1,446 older patients after elective cardiac surgery at the Sakakibara Heart Institute. We examined the association between HAD and 7 domains of frailty assessed by the Kihon Checklist. HAD was defined as a decline in the ability to perform activities of daily living (ADL) between admission and discharge, as assessed by the Barthel Index. Logistic regression and decision tree analysis were used to identify associations between the number and type of frailty components and HAD. Of the 1,446 patients, 190 were excluded, and 90 (7%) developed HAD. An increase in the number of frailty components was a risk factor for HAD (odds ratio: 1.88, 95% confidence interval: 1.62–2.17). Decision tree analysis identified physical functional decline, depression, and cognitive dysfunction as factors associated with HAD. The incidence of HAD was highest in cases of physical functional decline (21%) and lowest for cases in which the 3 aforementioned factors were absent (2.8%).

Conclusions: An increased number of frailty factors increased the risk of HAD and the findings also reaffirmed the importance of a comprehensive assessment to evaluate the risk of HAD, including evaluation of physical function, cognitive function, and depression.

Background: Heart failure (HF) is an increasing health problem associated with a high mortality rate. Growth differentiation factor (GDF) 15, a stress response cytokine belonging to the transforming growth factor-β superfamily, is associated with poor clinical outcomes in a broad spectrum of cardiovascular diseases. However, the prognostic usefulness of GDF15 in Japanese patients with HF remains unclear.

Methods and Results: We measured serum concentrations of GDF15 and B-type natriuretic peptide (BNP) in 1,201 patients with HF. All patients were prospectively followed for a median period of 1,309 days. In all, 319 HF-related events and 187 all-cause deaths occurred during the follow-up period. Kaplan-Meier analysis demonstrated that, among GDF15 tertiles, the highest tertile group had the greatest risk of HF-related events and all-cause mortality. Multivariate Cox proportional hazard regression analysis demonstrated that the serum GDF15 concentration was an independent predictor of HF-related events and all-cause deaths after adjusting for confounding risk factors. Serum GDF15 improved the prediction capacity for all-cause deaths and HF-related events with a significant net reclassification index and integrated discrimination improvement. Subgroup analysis in patients with HF with preserved ejection fraction also showed the prognostic usefulness of GDF15.

Conclusions: Serum GDF15 concentrations were associated with HF severity and clinical outcomes, indicating that GDF15 could provide additional clinical information to track the health status of patients with HF.

Background: Although guideline-directed medical therapy (GDMT), including β-blockers, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), improves survival and quality of life, most patients with heart failure with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction are treated with inadequate medications. We investigated the prescription patterns of GDMT in elderly patients with HFrEF and HFmrEF and their characteristics, including the certification of long-term care insurance (LTCI), which represents frailty and disability.

Methods and Results: This retrospective cross-sectional study analyzed 1,296 elderly patients with symptomatic HFrEF and HFmrEF with diuretic use (median age 78 years; 63.8% male; median left ventricular ejection fraction 40%). Prescription rates of GDMT were inadequate (ACEi, ARBs, β-blockers, and MRAs: 27.0%, 30.1%, 54.1%, and 41.9%, respectively). LTCI certification was independently associated with reduced prescription of all medications (ACEi/ARB: odds ratio [OR] 0.591, 95% confidence interval [CI] 0.449–0.778, P=0.001; β-blockers: OR 0.698, 95% CI 0.529–0.920, P<0.001; MRAs: OR 0.743, 95% CI 0.560–0.985, P=0.052). Patients with LTCI certification also had a high prevalence of polypharmacy and prescription of diuretics.

Conclusions: Vulnerable patients with LTCI may be an explanation for the challenges in implementing GDMT, and communicating is required for favorable heart failure care in this population.

Background: The applicability of the Stages of Change model for cardiovascular disease-related behaviors, such as smoking, exercise, diet, and sleep quality, is unclear.

Methods and Results: Using a large-scale epidemiological dataset, we found that baseline behavior change intention, as per the transtheoretical model, was associated with modifications of unhealthy lifestyles including cigarette smoking, physical inactivity, skipping breakfast, and poor sleep quality.

Conclusions: Our results suggest that an individual’s motivation to change assessed by a general questionnaire may contribute to lifestyle modification and potentially prevent subsequent cardiovascular disease.