Hiroyuki Iwano

Heart failure: What does ejection fraction have to do with it?

Heart failure (HF) occurs across the entire range of left ventricular (LV) ejection fractions (EF), not just reduced EF. Nearly half or more patients presenting with HF have a preserved EF>0.50 (HFpEF). Diastolic dysfunction is apparent in all patients with HF, regardless of EF. A preserved EF indicates that the end-diastolic volume is appropriate for the stroke volume, and a reduced EF indicates that the end-diastolic volume is enlarged relative to stroke volume (i.e. the LV is dilated). Most therapies proven to be effective in HF with a reduced EF (ACE-inhibitors, angiotensin receptor blockers, beta-blockers, and cardiac resynchronization) reverse LV dilation. These therapies have not been proven to be effective in HFpEF. Increasing c-GMP may be a treatment target in HFpEF, and potential ways of increasing c-GMP are being studied. Finally, comorbidities are important in HFpEF and are additional targets for therapy.

Left ventricular global strain for estimating relaxation and filling pressure: A multicenter study

BACKGROUND Speckle-tracking echocardiography (STE)-derived parameters may have better correlation with left ventricular (LV) relaxation and filling pressure than tissue Doppler-derived parameters. However, it has not been elucidated which parameter - strain or strain rate - and which direction of myocardial deformation - longitudinal or circumferential - is the most useful marker of LV relaxation and filling pressure. METHODSANDRESULTS We conducted a prospective multicenter study and compared the correlation of tissue Doppler- and STE-derived parameters with the time constant of LV pressure decay (τ) and LV mean diastolic pressure (MDP) in 77 patients. The correlation of early-diastolic mitral annular velocity (e´) with τ was weak (r=-0.32, P<0.01), and that of peak longitudinal strain (LS) was the strongest (r=-0.45, P<0.001) among the STE-derived parameters. There was a modest correlation between LVMDP and the ratio of early-diastolic inflow velocity (E) to e´ (E/e´) (r=0.50, P<0.001). In contrast, the ratio of E to LS (E/LS) correlated strongly with LVMDP (r=0.70, P<0.001). The correlation of E/LS with LVMDP was significantly better than that for E/e´ (P<0.01). Receiver-operating characteristic analysis showed that E/LS had the largest area under the curve for distinguishing elevated LVMDP (E/LS 0.86, E/e´ 0.74, E/A 0.67). CONCLUSIONS STE-derived longitudinal parameters correlated well with LV relaxation and filling pressure. In particular, E/LS could be more accurate than E/e´ for estimating LV filling pressure. (Circ J 2016; 80: 1163-1170).

Myocardial Shortening in 3 Orthogonal Directions and Its Transmural Variation in Patients With Nonobstructive Hypertrophic Cardiomyopathy

BACKGROUND Although longitudinal strain (LS) is known to be reduced in patients with hypertrophic cardiomyopathy (HCM), it has not been elucidated whether or not circumferential strain (CS) is reduced. We aimed to determine whether multidirectional and layer-specific myocardial strain is reduced in patients with nonobstructive HCM. METHODSANDRESULTS Speckle-tracking echocardiography was performed in 41 HCM patients and 27 control subjects. Segmental and global LS and CS were measured in the inner, mid, and outer layers. Global LS was significantly lower in the HCM group than in controls in the inner (-10.3±2.9 vs. -14.8±2.0%, P<0.001), mid (-8.7±2.6 vs. -13.8±1.9%, P<0.001), and outer (-7.2±2.6 vs. -11.9±1.9%, P<0.001) layers. Global CS was preserved in the inner layer (-23.8±4.7 vs. -24.3±3.3%, P=0.69) but reduced in the mid (-10.3±3.1 vs. -13.3±2.5%, P<0.001) and outer layers (-6.7±2.3 vs. -8.6±2.3%, P=0.002). Differences in CS between the inner and outer layers correlated with segmental relative wall thickness (r=-0.20, P=0.002). Furthermore, only the absolute value of global CS in the inner layer positively correlated with left ventricular ejection fraction (r=0.32, P<0.01) among these multidirectional and layer-specific strains. CONCLUSIONS In patients with HCM, not only the LS in all layers but also CS in the mid and outer layers was reduced, presumably reflecting impaired myocardial function. In contrast, CS in the inner layer was preserved, being associated with maintenance of chamber function.

Delay of left ventricular longitudinal expansion with diastolic dysfunction: impact on load dependence of e′ and longitudinal strain rate

The effect of diastolic dysfunction (DD) on the timing of left ventricular (LV) diastolic longitudinal and circumferential expansion and their load dependence is not known. This study evaluated the timing of the peak early diastolic LV inflow velocity (E), mitral annular velocity (e′), and longitudinal and circumferential global strain rates (SRE) in 161 patients in sinus rhythm. The intraventricular pressure difference (IVPD) from the left atrium to the LV apex was obtained using color M‐mode Doppler data to integrate the Euler equation. The diastolic function was graded according to the guidelines. In normals (N = 57), E, e′, longitudinal SRE, and circumferential SRE occurred nearly simultaneously during the IVPD. With DD (N = 104), e′ and longitudinal SRE were delayed occurring after the IVPD (e′: 18 ± 23 msec, longitudinal SRE: 13 ± 21 msec from the IVPD), whereas circumferential SRE (−8 ± 28 msec) and E (−2 ± 13 msec) were not delayed. The normal dependence of e′ and longitudinal SRE on IVPD was reduced in DD; while the relation of circumferential SRE and E to IVPD were unchanged in DD. Thus, normally, the LV expands symmetrically during early diastole and both longitudinal and circumferential expansions are related to the IVPD. With DD, early diastolic longitudinal LV expansion is delayed, occurring after the IVPD and LV filling, resulting in their relative independence from the IVPD. In contrast, with DD, circumferential SRE and mitral inflow are not delayed and their normal relation to the IVPD is unchanged.

Effects of Surgical Ventricular Reconstruction and Mitral Complex Reconstruction on Cardiac Oxidative Metabolism and Efficiency in Nonischemic and Ischemic Dilated Cardiomyopathy

OBJECTIVES The aim of this study was to investigate the effects of surgical ventricular reconstruction (SVR) on cardiac efficiency as a surrogate marker for cardiac function and oxidative metabolism in patients with severe heart failure. BACKGROUND Our new integrated overlapping left ventriculoplasty, modified SVR, combined with mitral complex reconstruction, reduce left ventricular (LV) volume associated with improvement of symptoms of heart failure. METHODS Twelve consecutive patients with end-stage heart failure due to nonischemic dilated cardiomyopathy (DCM) (n = 6) and ischemic dilated cardiomyopathy (ICM) (n = 6) who underwent SVR were studied. Myocardial oxidative metabolism per gram of tissue was estimated by monoexponential clearance of (11)C-acetate positron emission tomography (K(mono)). Forward stroke volume at the LV outflow tract was measured by echocardiography. Cardiac efficiency was estimated by the ratio of external work (stroke volume at the LV outflow tract index × systolic blood pressure × heart rate) to K(mono) before and 1 month after SVR. RESULTS After SVR, medians of New York Heart Association functional class significantly improved from 3 to 1.5 (p < 0.01) in both DCM and ICM patients. End-systolic and end-diastolic volume and LV mass significantly decreased in both groups. Stroke volume at the LV outflow tract increased from 43 ± 8 ml to 52 ± 11 ml (p = 0.028) in DCM patients, but not in ICM patients (49 ± 21 ml to 59 ± 26 ml, p = 0.12). K(mono) × LV mass, as an index of global LV oxidative metabolism, decreased in DCM patients (13.6 ± 1.9 g/min vs. 8.6 ± 1.5 g/min, p = 0.03) and ICM patients (12.0 ± 3.4 g/min vs. 9.2 ± 1.0 g/min, p = 0.06). As a result, cardiac efficiency increased in all patients with DCM (3.34 ± 0.46 × 10E6 vs. 4.74 ± 0.88 × 10E6 mm Hg·ml·min/m(2), p = 0.03) and in 5 of 6 patients with ICM (4.54 ± 1.66 × 10E6 vs. 5.99 ± 2.11 × 10E6 mm Hg·ml·min/m(2), p = 0.12). CONCLUSIONS Combined surgery with SVR and mitral complex reconstruction reduced LV volume in association with improvement of cardiac efficiency in patients with severe heart failure.

Value of Virtual Touch Quantification Elastography for Assessing Liver Congestion in Patients With Heart Failure

BACKGROUND Heart failure (HF) causes organ congestion, which is thought to increase organ stiffness. The virtual touch quantification (VTQ) method can be used to assess liver stiffness in patients with chronic liver diseases. This study aimed to measure liver and kidney stiffness using VTQ and to determine its value for assessing organ congestion in patients with HF. METHODSANDRESULTS This study included 10 normal subjects and 38 HF patients (age 52.3±16.7 years, left ventricular ejection fraction 27.0±9.4%, plasma B-type natriuretic peptide [BNP] 1,297.3±1,155.1 pg/ml). We investigated the relationships between clinical characteristics and hemodynamics and liver and kidney stiffness, and assessed the effects of medical treatment on these measurements. Liver stiffness was significantly higher in HF patients (1.17±0.13 m/s vs. 2.03±0.91 m/s, P=0.004) compared with normal subjects, but kidney stiffness was similar in both groups. Central venous pressure (CVP) (P=0.021) and BNP (P=0.025) were independent predictive factors for increased liver stiffness in HF patients. Liver stiffness decreased significantly from 2.37±1.09 to 1.27±0.33 m/s (P<0.001) after treatment. Changes in liver stiffness in HF patients significantly correlated with changes in CVP (R=0.636, P=0.014) and cardiac index (R=-0.557, P=0.039) according to univariate analysis, and with changes in CVP in multivariate analysis. CONCLUSIONS Liver stiffness measured by noninvasive VTQ methods can be used to assess liver congestion and therapeutic effects in patients with HF. (Circ J 2016; 80: 1187-1195).

Morphofunctional cardiac changes in pregnant women: associations with biomarkers

Objective This longitudinal study was performed to determine changes in echocardiography parameters in association with various biomarker levels in pregnancy/postpartum. Methods Fifty-one healthy pregnant women underwent echocardiography with simultaneous determination of blood levels of five biomarkers at each of the first, second and third trimesters of pregnancy, immediately postpartum within 1 week after childbirth and approximately 1 month postpartum. Data on 255 echocardiography scans (five times per woman) and biomarkers were analysed. Results Left ventricular end-diastolic dimension, left atrial (LA) volume index and left ventricular (LV) mass index increased with advancing gestation and reached the maximum immediately postpartum concomitant with the highest brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI) and creatine kinase MB levels. The inferior vena cava diameter was significantly reduced in the third trimester compared with that in the first trimester and the peak occurred immediately after childbirth. In 255 paired measurements, hs-TnI level was significantly positively correlated with LA volume index and LV mass index; BNP and NT-proBNP were significantly positively correlated with LA volume index and estimated glomerular filtration rate (eGFR) was significantly positively correlated with the average of early diastolic septal and lateral mitral annular velocity (e′). Conclusions Maximal cardiac changes in morphology occurred postpartum within 1 week after childbirth, not during pregnancy. BNP/NT-proBNP, hs-TnI and eGFR reflected cardiac changes in pregnancy.

Novel echocardiographic method to assess left ventricular chamber stiffness and elevated end-diastolic pressure based on time–velocity integral measurements of pulmonary venous and transmitral flows

Aims The detection of increased left ventricular (LV) chamber stiffness may play an important role in assessing cardiac patients with potential but not overt heart failure. A non-invasive method to estimate it is not established. We investigated whether the echocardiographic backward/forward flow volume ratio from the left atrium (LA) during atrial contraction reflects the LV chamber stiffness. Methods and results We studied 62 patients who underwent cardiac catheterization and measured their left ventricular end-diastolic pressure (LVEDP) and pressure increase during atrial contraction (ΔPa) from the LV pressure waveform. Using the echocardiographic biplane method of disks, we measured the LV volume change during atrial contraction indexed to the body surface area (ΔVa), and ΔPa/ΔVa was calculated as a standard for the LV operating chamber stiffness. Using pulsed Doppler echocardiography, we measured the time-velocity integral (TVI) of the backward pulmonary venous (PV) flow during atrial contraction (IPVA) and the ratio of IPVA to the PV flow TVI throughout a cardiac cycle (FPVA). We also measured the TVI of the atrial systolic forward transmitral flow (IA) and the ratio of the IA to the transmitral TVI during a cardiac cycle (FA) and calculated IPVA/IA and FPVA/FA. IPVA/IA and FPVA/FA were well correlated with ΔPa/ΔVa (r = 0.79 and r = 0.81) and LVEDP (r = 0.73 and r = 0.77). The areas under the ROC curve to discriminate LVEDP >18 mmHg were 0.90 for IPVA/IA and 0.93 for FPVA/FA. Conclusion The FPVA/FA, the backward/forward flow volume ratio from the LA during atrial contraction, is useful for non-invasive assessments of LV chamber stiffness and elevated LVEDP.

Reduced variability of visual left ventricular ejection fraction assessment with reference images: The Japanese Association of Young Echocardiography Fellows multicenter study

BACKGROUND Visual estimation of left ventricular ejection fraction (LVEF) is widely applied to confirm quantitative EF. However, visual assessment is subjective, and variability may be influenced by observer experience. We hypothesized that a learning session might reduce the misclassification rate. METHODS Protocol 1: Visual LVEFs for 30 cases were measured by 79 readers from 13 cardiovascular tertiary care centers. Readers were divided into 3 groups by their experience: limited (1-5 years, n=28), intermediate (6-11 years, n=26), and highly experienced (12-years, n=25). Protocol 2: All readers were randomized to assess the effect of a learning session with reference images only or feedback plus reference images. After the session, 20 new cases were shown to all readers following the same methodology. To assess the concordance and accuracy pre- and post-intervention, each visual LVEF measurement was compared to overall average values as a reference. RESULTS Experience affected the concordance in visual EF values among the readers. Groups with intermediate and high experience showed significantly better mean difference (MD), standard deviation (SD), and coefficient of variation (CV) than those with limited experience at baseline. The learning session with reference image reduced the MD, SD, and CV in readers with limited experience. The learning session with reference images plus feedback also reduced proportional bias. Importantly, the misclassification rate for mid-range EF cases was reduced regardless of experience. CONCLUSION This large multicenter study suggested that a simple learning session with reference images can successfully reduce the misclassification rate for LVEF assessment.

Refractory cardiac myocarditis associated with drug rash with eosinophilia and systemic symptoms syndrome due to anti-bipolar disorder drugs: a case report

Abstract Background Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug reaction accompanied by multiple organ dysfunction. Myocarditis is a manifestation, and once acute necrotizing eosinophilic myocarditis (ANEM) develops, the mortality rate is high. Case summary We report the case of a 37-year-old man who developed myocarditis associated with DRESS syndrome after starting treatment with lithium and quetiapine for bipolar disorder. At that time, he presented with fever, morbilliform eruption, lymphadenopathy, eosinophilia with atypical lymphocytes, and liver dysfunction; bipolar drugs were discontinued and oral prednisolone begun. Four months later, he was admitted to our institution with worsening skin rash and dyspnoea. Transthoracic echocardiography revealed reduced systolic function in both ventricles, and endocardial biopsy indicated hypersensitivity myocarditis. Cardiac function was temporarily normalized by high-dose prednisolone. However, the inflammation was persistent as shown by a re-elevation of troponin T and fall of left ventricular ejection fraction several months later; in addition, 18F-fluoro-deoxyglucose positron emission tomography with chest computed tomography (FDG-PET/CT) showed focal FDG uptake in the left ventricle. Despite additional treatment with mycophenolate mofetil, the cardiac function deteriorated further, and the patient eventually manifested refractory heart failure classified as New York Heart Association (NYHA) Class III. Myocardial biopsy showed myocyte necrosis associated with ANEM. Discussion This is the first case report of DRESS-associated myocarditis due to treatment for bipolar disorder. Although the pathophysiology remains incompletely understood, lithium and/or quetiapine can induce refractory myocarditis in DRESS syndrome. Regular measurements of troponin T and FDG-PET/CT are useful for assessing disease progression in DRESS-associated myocarditis.