In-hospital initiation of angiotensin receptor-neprilysin inhibition in acute heart failure: the PREMIER trial.

BACKGROUND AND AIMS: The efficacy and safety of early sacubitril/valsartan (Sac/Val) initiation after acute heart failure (AHF) has not been demonstrated outside North America. The present study aimed to evaluate the effect of in-hospital Sac/Val therapy initiation after an AHF episode on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in Japanese patients. METHODS: This was an investigator-initiated, multicentre, prospective, randomized, open-label, blinded-endpoint pragmatic trial. After haemodynamic stabilization within 7 days after hospitalization, eligible inpatients were allocated to switch from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to Sac/Val (Sac/Val group) or to continue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (control group). The primary efficacy endpoint was the 8-week proportional change in geometric means of NT-proBNP levels. RESULTS: A total of 400 patients were equally randomized, and 376 (median age 75 years, 31.9% women, de novo heart failure rate 55.6%, and median left ventricular ejection fraction 37%) were analysed. The per cent changes in NT-proBNP level geometric means at Weeks 4/8 were -35%/-45% (Sac/Val group) and -18%/-32% (control group), and their group ratio (Sac/Val vs. control) was 0.80 (95% confidence interval 0.68-0.94; P = .008) at Week 4 and 0.81 (95% confidence interval 0.68-0.95; P = .012) at Week 8, respectively. In the pre-specified subgroup analyses, the effects of Sac/Val were confined to patients with a left ventricular ejection fraction < 40% and were more evident in those in sinus rhythm and taking mineralocorticoid receptor antagonists. No adverse safety signal was evident. CONCLUSIONS: In-hospital Sac/Val therapy initiation in addition to contemporary recommended therapy triggered a greater NT-proBNP level reduction in Japanese patients hospitalized for AHF. These findings may expand the evidence on Sac/Val therapy in this clinical situation outside North America. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov (NCT05164653) and Japan Registry of Clinical Trials (jRCTs021210046).

Dapagliflozin Influences Ventricular Hemodynamics and Exercise-Induced Pulmonary Hypertension in Type 2 Diabetes Patients　- A Randomized Controlled Trial.

BACKGROUND: This prospective randomized multicenter open-label trial evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2-i) improves left ventricular (LV) pump function and suppresses elevation of LV filling pressure (LVFP) and right ventricular systolic pressure (RVSP) during exercise in type 2 diabetes mellitus (T2DM) patients.Methods and Results:Based on HbA1c and LV ejection fraction, 78 patients with poorly controlled T2DM were randomly assigned to D-group (dapagliflozin 5 mg/day add-on) or C-group (conventional therapy add-on). Physical examination, home and office blood pressure examination, blood tests, and echocardiography at rest and during ergometer exercise were performed at baseline and at 1.5 and 6 months after treatment. The primary endpoint was defined as the change in RVSP (mmHg) between baseline and 6-month follow up. The secondary endpoints were changes in LVFP (ratio), stroke volume index (SVi; mL/m2), and cardiac index (CI; L/min/m2). Both RVSP and LVFP during exercise significantly decreased from baseline to 6 months after starting treatment in the D-group (P<0.001). No changes to either parameter was observed in the C-group. The SVi and CI did not improve in either group. Both home and office blood pressure significantly decreased in the D-group. Decreases in HbA1c were somewhat greater in the C-group. CONCLUSIONS: Dapagliflozin significantly improved RVSP and LVFP during exercise in patients with T2DM and cardiovascular risk, which may contribute to favorable effects on heart failure.

Reversible T-wave inversions and neurogenic myocardial stunning in a patient with recurrent stress-induced cardiomyopathy.

A 72-year-old female was diagnosed as a stress-induced cardiomyopathy from apical ballooning pattern of left ventricular dysfunction without coronary artery stenosis after the mental stress. ECG showed the transient T-wave inversions after the ST-segment elevations. By the mental stress after 1 year, she showed a transient dysfunction with similar ECG changes again. T-wave inversions recovered earlier, and cardiac sympathetic dysfunction showed a lighter response corresponding to the less severe dysfunction than those after the first onset. Wellens' ECG pattern was associated with the degree of neurogenic myocardial stunning with sympathetic hyperinnervation caused by mental stress.

Prognostic value of left atrial reverse remodelling in patients hospitalized with acute decompensated heart failure.

AIMS: Left atrial (LA) volume index (LAVI) in chronic heart failure (HF) predicts cardiovascular outcomes. However, the association between LAVI reduction during acute decompensated HF (ADHF) and its prognostic potential is limited. We hypothesized that LA reverse remodelling (LARR) after ADHF therapy would be associated with better clinical outcomes. METHODS: This retrospective study analysed clinical outcomes and the LAVI reduction rate of 363 out of 861 patients hospitalized for ADHF who underwent two-point echocardiography at admission and discharge between January 2015 and December 2019. The mean age was 74.3 ± 13.6 years, and the mean ejection fraction (EF) was 38.9 ± 15.2%. The follow-up echocardiogram was performed 13.0 [9.5, 20] days after admission. As the median LAVI reduction rate was 7.02%, the LARR was defined as an LAVI reduction rate >7%. RESULTS: During the 34.0 ± 20.2 months of follow-up, 117 patients (32.2%) reached the primary endpoint defined as cardiovascular death and rehospitalization for ADHF. Kaplan-Meier survival analysis showed that patients with LARR had a better prognosis. Multivariate analysis indicated that LARR was an independent predictor of cardiovascular events. Similar findings were observed in the subgroup analyses of patients with persistent/permanent atrial fibrillation and those with non-HF with reduced EF. Among patients who were brain natriuretic peptide (BNP) responders, defined as a relative reduction of >70% in BNP from admission to discharge, non-LARR was observed in 41.6%. BNP responders without LARR experienced worse prognoses. CONCLUSIONS: LARR in the early vulnerable phase after hospitalization for ADHF was associated with better long-term clinical outcomes.

Cardiac Structure and Cardiorespiratory Fitness in Young Male Japanese Rugby Athletes.

Limited data are available on athlete's heart for rugby athletes. This study aimed to investigate cardiac structure and its relationship with cardiorespiratory fitness in young Japanese rugby athletes. A prospective cross-sectional study using echocardiography and cardiopulmonary exercise testing (CPET) was conducted on 114 male collegiate rugby players. There was a higher prevalence of increased left ventricular (LV), atrial, and aortic dimensions in the young athletes than that in previously published reports, whereas the wall thickness was within the normal range. Anthropometry and CPET analyses indicated that the forwards and backs presented muscular and endurance phenotypes, respectively. Indexed LV and aortic dimensions were significantly larger in the backs than in the forwards, and the dimensions significantly correlated with oxygen uptake measured by CPET. On the four-tiered classification for LV hypertrophy, abnormal LV geometry was found in 16% of the athletes. Notably, the resting systolic blood pressure was significantly higher in athletes with concentric abnormal geometry than in the other geometry groups, regardless of their field positions. Japanese young athletes may exhibit unique phenotypes of cardiac remodeling in association with their fitness characteristics. The four-tiered LV geometry classification potentially offers information regarding the subclinical cardiovascular risks of young athletes.

Anxiety disorder is associated with nocturnal and early morning hypertension with or without morning surge: ambulatory blood pressure monitoring.

BACKGROUND: Nocturnal and early morning hypertension are both significant risk factors for cardiovascular events. It remains unclear whether anxiety disorder affects nocturnal blood pressure (BP), early morning BP, or BP pattern in hypertensive patients. METHODS AND RESULTS: One hundred and twenty consecutive hypertensive outpatients (77 men and 43 women; mean age, 66±11 years) were divided into 2 groups based on Hospital Anxiety and Depression Scale (HADS) score: a control group (n=78; HADS ≤10) and an anxiety group (42 patients; HADS ≥11). Nocturnal BP, early morning BP, morning BP surge (defined as BP rise ≥50 mmHg), and BP pattern (extreme-dipper/dipper/non-dipper/riser) were measured on ambulatory BP monitoring. Clinical characteristics and BP were also evaluated at physician check-up. There was no significant difference between the 2 groups for BP check-up, but nocturnal and early morning BP were significantly higher in the anxiety group (142±16 mmHg and 152±21 mmHg) than in the control group (126±14 mmHg and 141±18 mmHg). With regard to patients with morning BP surge, nocturnal and early morning BP were also significantly higher in the anxiety group. The relative risk of existing anxiety disorders in riser-type hypertension was 4.48-fold higher (95% confidence interval: 1.58-12.74; P<0.005) than in dipper-type hypertension. CONCLUSIONS: Anxiety disorder is associated with nocturnal and early morning hypertension, and may be a risk factor for cardiovascular events.

Intraoperative Trifecta Valve Malfunction.

The Trifecta valve has been reported to have valve dysfunction months to years after operation. However there were no reports of intraoperative valve dysfunction. A 73-year-old man with aortic stenosis underwent aortic valve replacement using a 21-mm Trifecta valve with Glide Technology (Trifecta GT; Abbot). Hemodynamics were collapsed after aortic declamp because of severe regurgitation, and we replaced it with another biologic valve. We noticed that the removed valve's mount post was open outwardly more than usual. Despite the progress of the biologic valve, dysfunction like this case can occur during operation, and it is important to reoperate immediately even if there is no obvious tear or deformity.

CT findings in a patient with Coronavirus Disease-19-associated acute pericarditis.

Coronavirus Disease-19 (COVID-19)-associated acute pericarditis is a rare complication. Several cases have been reported, but those reports have not discussed any imaging findings. Here, we report a case of a 76-year-old female diagnosed with COVID-19-associated pericarditis without pneumonia, and present image findings of the patient's contrast-enhanced CT.

Predicting prognosis based on the shape of the left ventricular cavity in dilated cardiomyopathy: analysis using rate of improvement in the circle index.

PURPOSE: To elucidate the relation between a quantitative measure of the shape of the left ventricular cavity, cardiac function, and prognosis in patients with dilated cardiomyopathy (DCM). METHODS: The hearts of 20 healthy individuals and 18 patients with DCM were evaluated. Participants were aged 48.5 ± 5.0 years. On the basis of end-systolic four-chamber view echocardiograms, the endocardium of the left ventricle was traced and the resulting curve was segmented using 100 points. A line tangential to the curve was then drawn at each point, and the angle between two adjacent tangential lines was calculated. The deviation of these angles was designated as the circle index. The circle index and hemodynamic findings in patients with DCM were compared, and the rate of improvement in the circle index in these cases of DCM was determined. These patients were then placed into one of two groups: group R (11 patients), those with improvement rates of 10% or higher at time of discharge; and group NR (seven patients), those with rates less than 10%. Diuretic (furosemide) use, New York Heart Association (NYHA) classification, and readmission rate for the two groups were compared 2 years after discharge. RESULTS: The circle index was 2.7 ± 0.9 in the DCM group and 17.5 ± 4.2 in the healthy group (P < 0.01). The circle index in the DCM group was correlated with pulmonary capillary wedge pressure (r(2) = 0.42). Use of furosemide was unchanged in group R 2 years after discharge, but had increased for all patients in group NR. All cases in group R were classified as NYHA I 2 years after discharge. In group NR, in contrast, although all cases were classified as NYHA I at discharge, five of seven cases had deteriorated to NYHA III-IV 2 years later and were readmitted to hospital. CONCLUSION: There appears to be a quantifiable correlation between the circularity of the left ventricular cavity and the circle index. This suggests that rate of improvement after treatment for heart failure could predict prognosis in patients with DCM.

Impact of depression on masked hypertension and variability in home blood pressure in treated hypertensive patients.

This study was conducted to determine the effects of depression and/or insomnia on masked hypertension (MHT) compared with other types of HT and on variability in home-measured blood pressure (HBP) and clinic BP (CBP). Three hundred and twenty-eight hypertensives (132 women) aged 68±10 years were classified into four BP types: controlled HT (CHT), white-coat HT, MHT and sustained HT (SHT), based on CBP (140/90 mm Hg) and morning HBP (135/85 mm Hg) measurements. A score of ⩾16 on the Center for Epidemiologic Studies Depression Scale (CES-D) was defined as depression. The mean values and s.d. of BP were calculated from measurements taken during the 14 consecutive days just before the CES-D evaluation. Compared with the CHT group, the risk of depression was 2.77-fold higher in the SHT group and even higher in the MHT group (7.02-fold). The association between depression and MHT was augmented in the presence of insomnia and was somewhat stronger in women. A HBP variability index defined as s.d./mean BPs in both morning and night time was significantly higher in MHT than in the other BP types, whereas that of CBP was not. Both morning and night-time HBP variability were significantly higher in depressive patients than in non-depressives. These suggest that depression is associated with MHT and that increases both morning and night-time HBP variability but not CBP variability. Physicians should be mindful of mental stresses such as depression in their hypertensive patients when forming strategies to control BP over the diurnal cycle.

Adenosine triphosphate stress myocardial contrast echocardiography detects coronary artery stenosis with greater sensitivity than wall-motion abnormality measurements.

BACKGROUND: Although stress myocardial contrast echocardiography (MCE) can be used to detect coronary stenosis, its efficacy relative to other methods, such as detection of wall-motion abnormalities, remains unknown. Thus, the goal of this study was to compare the sensitivity of MCE versus wall-motion abnormality detection in the assessment of coronary artery stenosis. METHOD: Nine dogs with severe but nonflow limiting stenosis in the circumflex coronary artery underwent evaluation with real-time MCE along the short-axis view during infusion of Optison. The equation of y = a (1 - e -betat ) + c, which fits the replenishment curve of MCE, was calculated in the midseptum (normal region) and in the lateral wall (ischemic region) before and during adenosine triphosphate infusion. Wall-motion abnormalities were also evaluated by visual assessment and by measurement of wall thickening. RESULTS: Area under the receiver operating characteristic curve in beta- and A x beta-value, and percent wall thickening, was 0.963, 0.963, and 0.889, respectively, indicating that the diagnostic accuracy for detecting the coronary artery stenosis by real-time MCE was higher than that by the wall-motion assessment. CONCLUSION: Real-time MCE has higher sensitivity in detecting coronary stenosis during adenosine triphosphate stress test when compared with wall-motion assessment.

Myocardial blood flow parameters derived from contrast replenishment using harmonic power Doppler imaging are underestimated by ultrasound signal attenuation.

The effect of ultrasound signal attenuation on myocardial blood flow parameters derived from contrast replenishment was evaluated using harmonic gray-scale (HGS) and harmonic power Doppler (HPD) imaging. In vitro experiments were performed in a flow model, whereas in vivo experiments were performed in 5 open-chest dogs. In each study, intermittent HGS and HPD images were acquired at various pulsing intervals during contrast infusion. A silicone pad was interposed between the transducer and target region to simulate attenuation conditions. Baseline-subtracted HGS and HPD signal intensities were measured with and without silicone pad, and myocardial blood flow parameters A and beta were calculated using contrast replenishment. Attenuation with HGS images could be offset by baseline subtraction, as baseline images provided the reference for attenuation. However, attenuation with HPD images could not be compensated for, as baseline signal intensity was theoretically 0. In HGS mode, silicone attenuation produced no significant decreases in A and beta. In HPD mode, however, A and beta were significantly decreased by silicone attenuation (A, P <.001; beta, P <.05). Compared with nonattenuated regions, myocardial blood flow parameters in attenuated regions are underestimated when HPD imaging is used. Baseline-subtracted HGS imaging may be useful to compensate for thoracic wall attenuation.

Three-dimensional reconstruction of coronary arteriole plexus image by contrast echocardiography using a high-frequency transducer.

OBJECTIVE: This study was established to examine the efficacy of a high-frequency liner probe for visualizing fine anatomy of coronary microcirculation. METHODS: The vessel size and its velocity-time integral at the anterior wall in dogs by real-time contrast echocardiography with high-frequency liner probe and pulse Doppler methods, and the coronary flow volume, were measured before and after adenosine triphosphate injection. A 3-dimensional (3D) image was reconstructed by the built-in 3D system using intermittent flash echocardiographic images. RESULTS: The increments of flow volume calculated from vessel sizes and velocity-time integral were well correlated with those of coronary flow volume. Using intermittent flash echocardiographic images, fine dots and lines of contrast echocardiographic-expected arterioles were evident, and easily and quickly reconstructed as coronary plexus by 3D system. CONCLUSION: A high-frequency liner probe provides the fine-vessel images to evaluate those morphologic changes; a 3D reconstruction image could provide new information about coronary arterioles.

Brief communications: visualization of coronary arteries in rats by 3-dimensional real-time contrast echocardiography.

Angiogenesis is under intense investigation to advance the treatment of various ischemic diseases. Small animals, such as mice and rats, are often used for this purpose. However, evaluating the structure of coronary arteries in small animals in situ is not easy. We succeeded in visualizing the coronary artery in rats on 3-dimensional real-time contrast echocardiography using a high-frequency transducer. These methods will be applied for more convenient assessment in a new study, examining issues such as angiogenesis using rats in situ.

Quantitative assessment of microcollateral recruitment during coronary occlusion using real-time intravenous myocardial contrast echocardiography.

BACKGROUND: Residual collateral-derived myocardial blood flow (MBF) (A x beta) is important to protect against myocardial ischemia after acute coronary occlusion. METHODS: Recruitment of microcollateral was assessed in 22 dogs with left circumflex coronary artery occlusion by analysis of MBF and regional wall thickening (WT) using real-time myocardial contrast echocardiography. RESULTS: Video intensity and WT at the center of risk area were significantly lower than those at the border of risk area. The video intensity, A value, beta value, and MBF correlated well with WT after left circumflex coronary artery occlusion. The WT of the area with above 25% of normal MBF was preserved and was higher than that at below 25%. However, the deterioration of WT was not distinguished according to A value. CONCLUSION: Real-time myocardial contrast echocardiography is a useful noninvasive method to evaluate collateral-derived MBF, which can be a reliable index of protection against myocardial ischemia.

Effect of systemic blood pressure on microcollateral circulation evaluated by real-time contrast echocardiography.

BACKGROUND: In acute myocardial infarction, residual collateral-derived myocardial blood flow (CBF) within the ischemic area is one of the major determinants of infarct size. Management of systemic blood pressure (sBP) related to maintain collateral circulation is still difficult. The aim of this study was to reveal the influence of sBP on the rescue of area at risk by collateral circulation. METHODS: Real-time myocardial contrast echocardiography just after the onset of complete occlusion of the left circumflex coronary artery was performed in collateral-rich open-chest dogs. The video intensity of the ischemic area was evaluated during the occlusion and the CBF (A x beta) was calculated from a replenishment curve: y = A (1 - e(-beta t)). To analyze the effect of sBP on the collateral circulation, sBP was altered by infusion of nitroglycerin or etilefrine hydrochloride. To evaluate the defect size (%DS), every end-systolic myocardial contrast echocardiography image after left circumflex coronary artery occlusion was converted into binary images using custom offline software. RESULTS: The %DS increased and CBF slightly decreased at low sBP. The %DS decreased and CBF increased at high sBP. At excessively high sBP, %DS increased and CBF decreased again. CONCLUSION: Real-time myocardial contrast echocardiography, which is a useful noninvasive method to evaluate the collateral perfusion quantitatively, has a crucial role in the decision of patient treatment and management strategy of acute myocardial infarction.

Improved septal contraction and coronary flow velocity after cardiac resynchronization therapy elucidated by strain imaging and pulsed wave Doppler echocardiography.

OBJECTIVES: The effects of cardiac resynchronization therapy (CRT) with various atrioventricular conduction delay settings were investigated on cardiac hemodynamic changes involved in coronary flow velocity using color and pulsed wave Doppler modalities and myocardial regional contractility using a novel echocardiographic technique (strain imaging). METHODS: Seven patients with advanced heart failure (left ventricular ejection fraction < 35%) and left bundle branch block(QRS > or = 140 msec) were treated with CRT. Color and pulsed wave Doppler imaging were performed from the apical four-chamber view to examine the cardiac functions such as stroke volume, cardiac output, mitral regurgitant volume and coronary flow velocity. Strain imaging was performed to quantify the asynchrony of both intraventricular and interventricular time delay between the septum and left ventricular free wall (posterior wall) and to assess the regional contractile function. Wall motion was also evaluated. RESULTS: Intraventricular and interventricular asynchrony were improved from 173 +/- 18 to 60 +/- 6 msec, and 69 +/- 25 to 12 +/- 3 msec, respectively. Stroke volume (55.2 +/- 6.2 to 76.8 +/- 10.8 ml; 39% up), cardiac output (3.9 +/- 0.3 to 5.4 +/- 0.5 I/min; 38% up) and coronary flow velocity (24 +/- 3 to 36 +/- 5 cm/sec; 50% up) were greatly increased and mitral regurgitant volume (59.7 +/- 18.0 to 38.9 +/- 11.3 ml; 35% down)was clearly decreased. Septal wall shortening was greatly increased from 10.2 +/- 2.3% to 17.0 +/- 1.8% and septal wall motion (radial thickening)was also improved simultaneously. Atrioventricular interval settings influenced all above parameters. CONCLUSIONS: CRT improved the cardiac hemodynamics involved in coronary flow significantly due to both resynchronization of inter and intra asynchrony, and improvement of the regional myocardial contraction in patients with severe congestive heart failure and complete left bundle branch block.