Kazuaki Negishi

Use of speckle strain to assess left ventricular responses to cardiotoxic chemotherapy and cardioprotection

AIMS The variability of ejection fraction (EF) poses a problem in the assessment of left ventricular (LV) function in patients receiving potentially cardiotoxic chemotherapy. We sought to use global longitudinal strain (GLS) to compare LV responses to various cardiotoxic chemotherapy regimens and to examine the response to cardioprotection with beta-blockers (BB) in patients showing subclinical myocardial damage. METHODS AND RESULTS We studied 159 patients (49 ± 14 year, 127 women) receiving anthracycline (group A, n = 53, 46 ± 17 year), trastuzumab (group T, n = 61, 53 ± 12 year), or trastuzumab after anthracyclines (group AT, n = 45, 46 ± 9 year). LV indices [ejection fraction (EF), mitral annular systolic velocity, and GLS] were measured at baseline and follow-up (7 ± 7 months). Patients who decreased GLS by ≥11% were followed for another 6 months; initiation of BB was at the discretion of the clinician. Anthracycline dose was similar between group A and group AT (213 ± 118 vs. 216 ± 47 mg/m(2), P = 0.85). Although ΔEF was similar among the groups, attenuation of GLS was the greatest in group AT (group A, 0.7 ± 2.8% shortening; T, 1.1 ± 2.7%; and AT, 2.0 ± 2.3%; P = 0.003, after adjustment). Of 52 patients who decreased GLS by ≥-11%, 24 were treated with BB and 28 were not. GLS improved in BB groups (from -17.6 ± 2.3 to -19.8 ± 2.6%, P < 0.001) but not in non-BB groups (from -18.0 ± 2.0 to -19.0 ± 3.0%, P = 0.08). Effects of BB were similar with all regimens. CONCLUSIONS GLS is an effective parameter for identifying systolic dysfunction (which appears worst with combined anthracycline and trastuzumab therapy) and responds to cardioprotection in patients administered beta-blockers.

Left Atrial Strain Provides Incremental Value for Embolism Risk Stratification over CHA2DS2-VASc Score and Indicates Prognostic Impact in Patients with Atrial Fibrillation

BACKGROUND The aim of this study was to investigate whether left atrial (LA) strain has incremental value over the CHA2DS2-VASc score for stratifying the risk for embolism in patients with atrial fibrillation (AF) and whether LA strain predicts poststroke mortality. METHODS Consecutive patients with paroxysmal or persistent AF with acute embolism (82 patients) or without (204 controls) were prospectively enrolled. Global peak LA longitudinal strain during ventricular systole (LAS) was assessed during AF rhythm. Global LAS was compared between the groups in the first cross-sectional study. Then, the 82 patients with acute embolism were prospectively followed during the second prospective cohort study. RESULTS Global LAS was lower in patients with acute embolism than in controls (P < .001). Global LAS < 15.4% differentiated patients with acute embolism from controls, with an area under the curve of 0.83 (P < .0001). In multivariate analysis, global LAS was independently associated with acute embolism (odds ratio, 0.74; 95% confidence interval, 0.67-0.82; P < .001) and had an incremental value over the CHA2DS2-VASc score (P < .0001). Furthermore, 26 patients with acute embolisms died during a median follow-up period of 425 days. Global LAS independently predicted mortality after embolism. CONCLUSIONS In this observational study, LA strain provided incremental diagnostic information over that provided by the CHA2DS2-VASc score, suggesting that LA strain analysis could improve the current risk stratification of embolism in patients with AF. LA strain can also predict poststroke mortality.

Practical guidance in echocardiographic assessment of global longitudinal strain

there has been increasing interest in the measurement of global myocardial strain because it is a sensitive and robust index to detect subclinical myocardial dysfunction, with a defined normal range [(1)][1]. Numerous commercially-available versions of speckle tracking software are available for

Prognostic value of LA volumes assessed by transthoracic 3D echocardiography: comparison with 2D echocardiography.

OBJECTIVES The hypothesis of this study was that minimal left atrial volume index (LAVImin) by 3-dimensional echocardiography (3DE) is the best predictor of future cardiovascular events. BACKGROUND Although maximal left atrial volume index (LAVImax) by 2-dimensional echocardiography (2DE) is a robust index for predicting prognosis, the prognostic value of LAVImin and the superiority of measurements by 3DE over 2DE have not been determined in a large group of patients. METHODS In protocol 1, we assessed age and sex dependency of LAVIs using 2DE and 3DE in 124 normal subjects and determined their cutoff values (mean + 2 SD). In protocol 2, 2-dimensional (2D) and 3-dimensional (3D) LAVImax/LAVImin were measured in 556 patients with high prevalence of cardiovascular disease. After excluding patients with atrial fibrillation, mitral valve disease, and age <18 years, 439 subjects were followed to record major adverse cardiovascular events (MACE). Patients were divided into 2 groups by the cutoff criteria of LAVI in each method. RESULTS In protocol 1, there was no significant age and sex dependency for each 2D and 3D LAVI. In protocol 2, during a mean of 2.5 years of follow-up, MACE developed in 88 patients, including 32 cardiac deaths. Kaplan-Meier survival analyses showed that all 4 LAVI cutoff criteria had significant predictive power of MACE. After variables were adjusted for clinical variables and left ventricular ejection fraction, all 4 methods were still independently and significantly associated with MACE, but 3D-derived LAVImin had the highest risk ratio. 3D LAVImin also had an incremental prognostic value over 3D LAVImax. CONCLUSIONS LAVIs by both 2DE and 3DE are powerful predictors of future cardiac events. 3D LAVImin tended to have a stronger and additive prognostic value than 3D LAVImax.

Role of Temporal Resolution in Selection of the Appropriate Strain Technique for Evaluation of Subclinical Myocardial Dysfunction

Objective: To assess the effects of frame and volume rate on the concordance between two‐dimensional speckle tracking strain (2DS) and three‐dimensional speckle tracking strain (3DS), and between 2DS and triplane imaging of speckle tracking (Tri‐P). Methods: Global longitudinal strains (GLSs) derived from 2DS, 3DS, and Tri‐P were compared among 142 prospectively recruited patients who underwent evaluation of subclinical left ventricle (LV) function. Results: Feasibility to obtain GLS of 3DS was significantly higher than that of Tri‐P (76% vs. 47%, P < 0.001). The correlation between 2DS and 3DS was only modest (r = 0.47) whereas that of 2DS and Tri‐P was better (r = 0.67). The difference in frame/volume rate between two methods also affected their correlation. A volume rate between 34 and 50 volumes/sec had the highest correlation between 2DS and 3DS (r = 0.72). The correlation between 2DS and Tri‐P was better with a difference in frame‐rate ≤20 per second than with a difference >20 per second. Likewise, there was a better correlation between 2DS and 3DS when the difference between 2D frame rate and 3D volume rate was ≤40 per second, compared to when it was >40 per second. These associations differed from segment to segment and the apical segments had the highest correlation and the basal the lowest. Conclusions: The feasibility of each means of strain calculation showed important differences, with 2DS being the most attainable. Strain values were not interchangeable among 2DS, Tri‐P, and 3DS. Importantly, poor correlations seemed to be driven by differences in acquisition rate. Currently, 2DS offers the most robust measurement of subclinical myocardial dysfunction. (Echocardiography 2012;29:334‐339)

Validation of Global Longitudinal Strain and Strain Rate as Reliable Markers of Right Ventricular Dysfunction: Comparison with Cardiac Magnetic Resonance and Outcome

Background Right ventricular (RV) dysfunction in ischemic cardiomyopathy (ICM) is associated with poor prognosis, but RV assessment by conventional echocardiography remains difficult. We sought to validate RV global longitudinal strain (RVGLS) and global longitudinal strain rate (RVGLSR) against cardiac magnetic resonance (CMR) and outcome in ICM. Methods In 57 patients (43 men, 64 ± 12 years) with ICM who underwent conventional and strain echocardiography and CMR, RVGLS and RVGLSR were measured off-line. RV dysfunction was determined by CMR [RV ejection fraction (RVEF) < 50%]. Patients were followed over 15 ± 9 months for a composite of death and hospitalization for worsening heart failure. Results RVGLS showed significant correlations with CMR RVEF (r = -0.797, p < 0.01), RV fractional area change (RVFAC, r = -0.530, p < 0.01), and tricuspid annular plane systolic excursion (TAPSE, r = -0.547, p < 0.01). RVGLSR showed significant correlations between CMR RVEF (r = -0.668, p < 0.01), RVFAC (r = -0.394, p < 0.01), and TAPSE (r = -0.435, p < 0.01). RVGLS and RVGLSR showed significant correlations with pulmonary vascular resistance (r = 0.527 and r = 0.500, p < 0.01, respectively). The best cutoff value of RVGLS for detection of RV dysfunction was -15.4% [areas under the curve (AUC) = 0.955, p < 0.01] with a sensitivity of 81% and specificity 95%. The best cutoff value for RVGLSR was -0.94 s-1 (AUC = 0.871, p < 0.01), sensitivity 72%, specificity 86%. During follow-up, there were 12 adverse events. In Cox-proportional hazard regression analysis, impaired RVGLS [hazard ratio (HR) = 5.46, p = 0.030] and impaired RVGLSR (HR = 3.95, p = 0.044) were associated with adverse clinical outcome. Conclusion Compared with conventional echocardiographic parameters, RVGLS and RVGLSR correlate better with CMR RVEF and outcome.

Normal ranges of left atrial strain by speckle-tracking echocardiography: A systematic review and meta-analysis

Background: Recent advances in the assessment of myocardial function have facilitated the direct measurement of atrial function using speckle‐tracking echocardiography. Currently, normal reference ranges for atrial function using speckle‐tracking echocardiography are based on a few initial studies, with variations among modestly sized (n = 100–350) studies. Methods: The authors searched the PubMed, Embase, and Scopus databases for the key terms “left atrial/atrial/atrium” and “strain/function/deformation/stiffness” and “speckle tracking/Velocity Vector Imaging/edge tracking.” Studies of global left atrial function using speckle‐tracking were selected if they involved >30 normal or healthy participants without any cardiac risk factors. Normal ranges for reservoir strain, conduit strain, and contractile strain were computed using a random‐effects model. Meta‐regression and subgroup analysis was performed to explore between‐study heterogeneity. Results: Forty studies (2,542 healthy subjects) satisfied the inclusion criteria. Meta‐analysis revealed a normal reference range for reservoir strain of 39% (95% CI, 38%–41%, from 40 articles), for conduit strain of 23% (95% CI, 21%–25%, from 14 articles), and for contractile strain of 17% (95% CI, 16%–19%, from 18 articles). Meta‐regression identified heart rate (P = .02) and body surface area (P = .003) as contributors to this heterogeneity. Subgroup analyses revealed heterogeneity due to sample size (n > 100 vs N < 100, P = .02). Conclusions: The normal reference ranges for the three components of left atrial function are demonstrated. The between‐study heterogeneity is explained partly by heart rate, body surface area, and sample size.

Impact of repeat myocardial revascularization on outcome in patients with silent ischemia after previous revascularization

OBJECTIVES This study sought to compare the survival of asymptomatic patients with previous revascularization and ischemia, who subsequently underwent repeat revascularization or medical therapy (MT). BACKGROUND Coronary artery disease is progressive and recurring; thus, stress myocardial perfusion scintigraphy (MPS) is widely used to identify ischemia in patients with previous revascularization. METHODS Of 6,750 patients with previous revascularization undergoing MPS between January 1, 2005, and December 31, 2007, we identified 769 patients (age 67.7 ± 9.5 years; 85% men) who had ischemia and were asymptomatic. A propensity score was developed to express the associations of revascularization. Patients were followed up over a median of 5.7 years (interquartile range: 4.7 to 6.4 years) for all-cause death. A Cox proportional hazards model was used to identify the association of revascularization with all-cause death, with and without adjustment for the propensity score. The model was repeated in propensity-matched groups undergoing MT versus revascularization. RESULTS Among 769 patients, 115 (15%) underwent revascularization a median of 13 days (interquartile range: 6 to 31 days) after MPS. There were 142 deaths; mortality with MT and revascularization were 18.3% and 19.1% (p = 0.84). In a Cox proportional hazards model (chi-square test = 89.4) adjusting for baseline characteristics, type of previous revascularization, MPS data, and propensity scores, only age and hypercholesterolemia but not revascularization were associated with mortality. This result was confirmed in a propensity-matched group. CONCLUSIONS Asymptomatic patients with previous revascularization and inducible ischemia on MPS realize no survival benefit from repeat revascularization. In this group of post-revascularization patients, an ischemia-based treatment strategy did not alter mortality.

Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals

Background: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important components of phospholipids and cell membranes. There has, however, been no clinical report on the direct effects of ARA and DHA on coronary circulation. Objective: To evaluate the effects of ARA and DHA on coronary circulation using the measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE). Methods: A double-blind, placebo-matched study of 28 Japanese elderly individuals (19 men, mean age 65 years) conducted to compare the effects of polyunsaturated fatty acids (PUFA; ARA 240 mg/day, DHA 240 mg/day) and placebo on CFVR. Coronary flow velocity (CFV) of the left anterior descending coronary artery was measured at rest and during hyperaemia by TTDE to determine CFVR. Results: There were no significant differences in CFV at rest or during hyperaemia in CFVR at baseline in the two groups (PUFA versus placebo 17 (7 SD) versus 16 (6), 62 (20) versus 59 (12), and 3.85 (1.04) versus 3.98 (0.83) cm/s, respectively). After three months’ supplementation, CFV during hyperaemia was significantly higher in the PUFA than in the placebo group (73 (19) versus 64 (12) cm/s, p<0.01) although no significant difference was found between the two groups in CFV at rest (17 (7) versus 16 (4) cm/s). CFVR thus significantly increased after PUFA consumption (3.85 (1.04) versus 4.46 (0.95), p = 0.0023). Conclusion: Three months’ supplementation of PUFA increased CFVR in Japanese elderly individuals, which suggests beneficial effects of PUFA on the coronary microcirculation.

Clinical prediction of incident heart failure risk: a systematic review and meta-analysis

Background Early treatment may alter progression to overt heart failure (HF) in asymptomatic individuals with stage B HF (SBHF). However, the identification of patients with SBHF is difficult. This systematic review sought to examine the strength of association of clinical factors with incident HF, with the intention of facilitating selection for HF screening. Methods Electronic databases were systematically searched for studies reporting risk factors for incident HF. Effect sizes, typically HRs, of each risk variable were extracted. Pooled crude and adjusted HRs with 95% CIs were computed for each risk variable using a random-effects model weighted by inverse variance. Results Twenty-seven clinical factors were identified to be associated with risk of incident HF in 15 observational studies in unselected community populations which followed 456 850 participants over 4–29 years. The strongest independent associations for incident HF were coronary artery disease (HR=2.94; 95% CI 1.36 to 6.33), diabetes mellitus (HR=2.00; 95% CI 1.68 to 2.38), age (HR (per 10 years)=1.80; 95% CI 1.13 to 2.87) followed by hypertension (HR=1.61; 95% CI 1.33 to 1.96), smoking (HR=1.60; 95% CI 1.45 to 1.77), male gender (HR=1.52; 95% CI 1.24 to 1.87) and body mass index (HR (per 5 kg/m2)=1.15; 95% CI 1.06 to 1.25). Atrial fibrillation (HR=1.88; 95% CI 1.60 to 2.21), left ventricular hypertrophy (HR=2.46; 95% CI 1.71 to 3.53) and valvular heart disease (HR=1.74; 95% CI 1.07 to 2.84) were also strongly associated with incident HF but were not examined in sufficient papers to provide pooled hazard estimates. Conclusions Prediction of incident HF can be calculated from seven common clinical variables. The risk associated with these may guide strategies for the identification of high-risk people who may benefit from further evaluation and intervention.