Masaki Tanabe

Elevated Cardiac Troponin I and Relationship to Persistence of Electrocardiographic and Echocardiographic Abnormalities After Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— Cardiac injury persistence after aneurysmal subarachnoid hemorrhage (aSAH) is not well described. We hypothesized that post-aSAH cardiac injury, detected by elevated cardiac troponin I (cTnI), is related to aSAH severity and associated with electrocardiographic and structural echocardiographic abnormalities that are persistent. Methods— Prospective longitudinal study was conducted of patients with aSAH with Fisher grade ≥2 and/or Hunt/Hess grade ≥3. Serum cTnI was collected on Days 1 to 5; cohort dichotomized into peak cTnI ≥0.3 ng/mL (elevated) or cTnI <0.3 ng/mL. Relationships among cTnI and aSAH severity, 12-lead electrocardiography early (≤4 days) and late (≥7 days), Holter monitoring on Days 1 to 5, and transthoracic echocardiogram (left ventricular ejection fraction and regional wall motion abnormalities) early (Days 0 to 5) and late (Days 5 to 12) were evaluated. Results— Of 204 subjects, 31% had cTnI ≥0.3 ng/mL. cTnI ≥0.3 ng/mL was incrementally related to aSAH severity by admission symptoms (Hunt/Hess P=0.001) and blood load (Fisher P=0.028). More patients with cTnI ≥0.3 ng/mL had prolonged QTc on early (63% versus 30%, P<0.0001) and late electrocardiography (24% versus 7%, P=0.024). On Holter monitoring, more patients with cTnI ≥0.3 ng/mL had ventricular tachycardia/fibrillation (22% versus 9%, P=0.018) but not atrial fibrillation/flutter (P=0.241). Cardiac troponin I ≥0.3 ng/mL was associated with both early ejection fraction <50% (44% versus 5%, P<0.0001) and regional wall motion abnormalities (44% versus 4%, P<0.0001). Regional wall motion abnormalities predominated in basal and midventricular segments and persisted to some degree in 73% of patients affected, whereas ejection fraction <50% persisted in 59% of patients affected. Conclusions— Cardiac injury is incrementally worse with increasing aSAH severity and associated with persistent QTc prolongation and ventricular arrhythmias. Regional wall motion abnormalities and depressed ejection fraction persist to some degree in the majority of those affected.

Echocardiographic Speckle Tracking Radial Strain Imaging to Assess Ventricular Dyssynchrony in a Pacing Model of Resynchronization Therapy

BACKGROUND Speckle tracking imaging is a promising new echocardiographic method to assess left ventricular (LV) mechanical dyssynchrony. Our aim was to assess a new speckle tracking regional strain algorithm by comparison with angle-corrected tissue Doppler (TD) in an animal model of left bundle branch block and cardiac resynchronization therapy. METHODS AND RESULTS Ten open-chest dogs had routine gray-scale and TD images of the mid-LV short-axis plane. Electrical activation was altered by pacing from right ventricular, LV free wall, and biventricular sites to create various degrees of mechanical dyssynchrony and alter regional function. Segmental time to peak strain, peak strain, and frame-by-frame strain were measured by angle-corrected TD, TD M-mode, and speckle tracking on the same digital cineloop. Of 240 possible paired TD and speckle tracking segments, data were available for 222 segments (93%); images with catheter artifacts were prospectively excluded. Comparative overall time to peak strain by each method correlated well: r = 0.96, bias = -6 +/- 20 ms. Of 80 possible paired M-mode TD and speckle tracking segments, strain data were available for 76 segments (95%). Comparative overall time to peak strain, peak strain, and frame-by-frame strain analysis in 1012 frames by each method correlated well: r = 0.98, bias of 1 +/- 14 ms; r = 0.82, bias of 3% +/- 7%; and r = 0.91, bias of 0% +/- 6%, respectively. CONCLUSION Regional strain analysis using echocardiographic speckle tracking radial strain strongly correlated with strain by angle-corrected TD imaging in an animal model of dyssynchrony. Speckle tracking radial strain has potential for clinical applications.

Left ventricular contraction-relaxation coupling in normal, hypertrophic, and failing myocardium quantified by speckle-tracking global strain and strain rate imaging.

OBJECTIVE The aim of this study was to noninvasively quantify global left ventricular (LV) contraction and relaxation, and to investigate their relationship in normal, hypertrophic, and failing myocardium. METHODS Fifty patients with hypertensive LV hypertrophy (LVH) (LVH group), 50 patients with dilated cardiomyopathy (DCM) (DCM group), and 50 normal subjects (control group) had echocardiographic evaluations. Global LV peak systolic strain (PSS) and peak relaxation rate (PRR) during early diastole were analyzed by speckle-tracking strain and strain rate imaging in the longitudinal and circumferential directions. RESULTS Both global PSS and PRR were reduced in the LVH group in the longitudinal direction. In the circumferential direction, global PSS was maintained and global PRR was reduced in the LVH group. The reductions in both global PSS and PRR were more pronounced in both directions in the DCM group compared with the other 2 groups. Global PSS correlated strongest with global PRR among the clinical and echocardiographic variables, which exhibited the best fit with exponential regressions in both the longitudinal and circumferential directions in all subjects (longitudinal: y=0.15e(-0.10x), r2=0.75; circumferential: y=0.21e(-0.09x), r2=0.76, P<.01, respectively). Multiple regression analysis indicated that global PSS was the most powerful determinant of global PRR in both longitudinal and circumferential directions. CONCLUSION Global LV function quantified using speckle-tracking echocardiography revealed strong coupling of LV contraction to relaxation sequentially from normal to failing myocardium, regardless of their heterogeneous pathophysiology. In addition, the extent of myocardial systolic shortening was the most powerful independent contributor of LV relaxation in both the longitudinal and circumferential directions. These results strongly indicate that LV myocardial systolic contraction directly regulates its relaxation.

Impact of heart rate on mechanical dyssynchrony and left ventricular contractility in patients with heart failure and normal QRS duration

The quantification of mechanical dyssynchrony has important diagnostic value and may help to determine optimal therapy in heart failure (HF). We hypothesized that mechanical dyssynchrony may be augmented at increased heart rates in patients with HF and normal QRS duration.

Reversible left ventricular regional non-uniformity quantified by speckle-tracking displacement and strain imaging in patients with acute pulmonary embolism.

BACKGROUND The aim of this study was to investigate the impact of acute right ventricular pressure overload (RVPO) on left ventricular (LV) function and regional uniformity using speckle-tracking displacement and strain analyses in patients with acute pulmonary embolism (PE). METHODS Twenty-five patients with acute PE (mean age, 59 ± 16 years) and 25 normal subjects were enrolled. Radial, longitudinal, and circumferential LV wall motion and myocardial deformation were analyzed using speckle-tracking displacement and strain imaging echocardiography, respectively, from the mid-LV short-axis and apical four-chamber views. The standard deviation of the heart rate-corrected intervals from QRS onset to peak systolic displacement (PSD) and peak systolic strain for the six segments was used to quantify LV systolic dyssynchrony. The standard deviation of regional PSD and peak systolic strain divided by their global values was used to quantify LV systolic heterogeneity. Mechanical discoordination of LV regional wall motion and myocardial deformation was assessed by averaging the frame-by-frame percentage discordance between segmental and global signal changes in the six segments. RESULTS Patients with acute PE had reduced radial PSD and peak systolic strain and a large extent of displacement-derived nonuniformities (PSD dyssynchrony, 74 ± 32 vs 40 ± 20 m sec; PSD heterogeneity, 0.39 ± 0.13 vs 0.17 ± 0.08; and PSD discoordination, 23 ± 2% vs 15 ± 3%; P < .05 vs normal subjects for all comparisons) associated with a leftward shift of the interventricular septum. In contrast, all indices of strain-derived radial LV nonuniformities were not augmented by acute RVPO in patients with acute PE. Patients with acute PE also had impaired LV systolic function and regional uniformities in the longitudinal and circumferential directions. After the amelioration of acute RVPO by primary treatment, most of the indices of LV function and regional uniformity were restored to normal values. Multiple regression analysis indicated that only radial LV wall motion discoordination was a significant determinant of cardiac index. CONCLUSIONS Acute RVPO induces reversal LV regional uniformities, which are closely associated with reduced LV function and abnormal geometry of the left ventricle, and radial LV wall motion coordination plays a key role in the short-term regulation of cardiac output in patients with acute PE.

Japanese antimicrobial consumption surveillance: First report on oral and parenteral antimicrobial consumption in Japan (2009–2013)

No reliable national antimicrobial consumption data have been available in Japan. The Japanese antimicrobial consumption surveillance (JACS) project started to collect data nationwide on antimicrobial consumption. This paper provides the first sales data from the JACS project on oral and parenteral antimicrobial consumption in Japan as well as the trends for the years from 2009 to 2013. The population-weighted total consumption was expressed as defined daily doses (DDDs) per 1000 inhabitants per day (DID). The value of DID increased from 14.7 in 2009 to 15.8 in 2013. Notably, oral antimicrobials accounted for 92.6% (mean of 2009, 2011 and 2013) of total consumption. Oral third-generation cephalosporins, macrolides and fluoroquinolones accounted for 77.1% (mean of 2009, 2011 and 2013) of oral consumption. Consumption of antimicrobials has increased during the years 2009 and 2013 regardless of the dosage form. This is the first report regarding the population-weighted consumption of oral and parenteral antimicrobials in Japan during the years 2009 and 2013. These results provide useful information for combating the menace of antimicrobial resistance in Japan.

Nitroglycerin improves left ventricular relaxation by changing systolic loading sequence in patients with excessive arterial load

Nitroglycerin abbreviates left ventricular (LV) relaxation through improved hemodynamics as well as by direct actions on the myocardium. The aim of this study was to examine whether the changing systolic loading sequence during nitroglycerin administration affects LV relaxation in patients with excessive arterial load. By use of a conductance catheter with microtip manometer, the effects of intravenous nitroglycerin (0.3-0.5 μg/kg/min) on LV function and hemodynamics were examined in 39 patients with various degrees of LV contractility. Patients were divided into two groups according to LV-arterial coupling, the ratio of end-systolic elastance (Ees) to effective arterial elastance (Ea). In patients with Ees/Ea ratio > 1, nitroglycerin had no effect on the time to peak force or on the time constant of LV relaxation (τ). On the other hand, in patients with Ees/Ea < 1, which represented excessive arterial load, nitroglycerin significantly shortened the time to peak force, shifted the peak of the loading sequence from late to early systole, and significantly decreased τ without any changes in Ees. Thus, nitroglycerin improved LV relaxation in patients with excessive arterial load partly by changing the systolic loading sequence.

Quantifying the role of regional dyssynchrony on global left ventricular performance.

OBJECTIVES We hypothesize that left ventricular (LV) segmental dyssynchrony, quantified by paradoxical systolic wall thinning, determines changes in global LV performance in a model of canine right ventricular (RV) pacing-induced dyssynchrony and the response to cardiac resynchronization therapy (CRT). BACKGROUND Quantification of LV dyssynchrony is important to assess the impact of CRT. METHODS Seven pentobarbital-anesthetized open-chest dogs had LV pressure-volume relations and mid-LV short-axis echocardiographic speckle tracking radial strain imaging during right atrial (RA) pacing, RV pacing to simulate left bundle branch block, and CRT using RV pacing plus either LV free-wall (CRTfw) and apical (CRTa) pacing. The area under the segmental LV time-radial strain positive and negative curves defined global thickening and thinning, respectively. Dyssynchrony was defined as the maximum time difference between earliest and latest peak segmental positive strain among 6 radial sites. RESULTS RA pacing had minimal dyssynchrony (58 + or - 40 ms). RV pacing induced both dyssynchrony (213 + or - 67 ms, p < 0.05) and reduced LV stroke work (SW) (67 + or - 51 mJ, p < 0.05). CRTfw and CRTa decreased dyssynchrony (116 + or - 47 ms and 50 + or - 34 ms, respectively, p < 0.05 vs. RV pacing), but only CRTa restored LV SW to RA pacing levels. RV pacing decreased global thickening (129 + or - 87%.ms) compared with RA pacing (258 + or - 133%.ms, p < 0.05), whereas CRTfw and CRTa restored regional thickening to RA pacing levels (194 + or - 83%.ms and 230 + or - 76%.ms, respectively). The sum of thickening and thinning during RV (230 + or - 88%.ms vs. 258 + or - 133%.ms, p < 0.05) correlated (r = 0.98) with RA thickening, suggesting that all the loss of LV function was due to thinning. CONCLUSIONS Dyssynchrony causes proportional changes in regional LV wall thinning and global LV SW that were reversed by CRT, suggesting that dyssynchrony impairs LV systolic function by causing paradoxical regional wall thinning and that CRT effectiveness can be monitored by its reversal. Thus, monitoring paradoxical regional thinning reversal may be used to define CRT effectiveness.

Impact of Chronic Kidney Disease on the Presence and Severity of Aortic Stenosis in Patients at High Risk for Coronary Artery Disease

ObjectiveWe evaluated the impact of chronic kidney disease (CKD) on the presence and severity of aortic stenosis (AS) in patients at high risk for coronary artery disease (CAD).MethodsOne hundred and twenty consecutive patients who underwent invasive coronary angiography were enrolled. Aortic valve area (AVA) was calculated by the continuity equation using transthoracic echocardiography, and was normalized by body surface area (AVA index).ResultsAmong all 120 patients, 78% had CAD, 55% had CKD (stage 3: 81%; stage 4: 19%), and 34% had AS (AVA < 2.0cm2). Patients with AS were older, more often female, and had a higher frequency of CKD than those without AS, but the prevalence of CAD and most other coexisting conventional risk factors was similar between patients with and without AS. Multivariate linear regression analysis indicated that only CKD and CAD were independent determinants of AVA index with standardized coefficients of -0.37 and -0.28, respectively. When patients were divided into 3 groups (group 1: absence of CKD and CAD, n = 16; group 2: presence of either CKD or CAD, n = 51; and group 3: presence of both CKD and CAD, n = 53), group 3 had the smallest AVA index (1.19 ± 0.30*# cm2/m2, *p < 0.05 vs. group 1: 1.65 ± 0.32 cm2/m2, and #p < 0.05 vs. group 2: 1.43 ± 0.29* cm2/m2) and the highest peak velocity across the aortic valve (1.53 ± 0.41*# m/sec; *p < 0.05 vs. group 1: 1.28 ± 0.29 m/sec, and #p < 0.05 vs. group 2: 1.35 ± 0.27 m/sec).ConclusionCKD, even pre-stage 5 CKD, has a more powerful impact on the presence and severity of AS than other conventional risk factors for atherosclerosis in patients at high risk for CAD.

Addition of Angiotensin II Receptor Antagonist to an ACE Inhibitor in Heart Failure Improves Cardiovascular Function by a Bradykinin-Mediated Mechanism

Whether cardiovascular responses to bradykinin are augmented by additional treatment with angiotensin II receptor antagonism (ATRA) to angiotensin-converting enzyme inhibition (ACEI) in congestive heart failure (CHF) is unknown. To clarify the level and functional effects of endogenous bradykinin in CHF with combined ATRA and ACEI, 35 dogs were assigned to the following treatment protocols: 1) rapid ventricular pacing (240 bpm), 2) concomitant ATRA (TCV116, 1.5 mg·kg−1·day−1) and rapid pacing, 3) concomitant ACEI (enalapril 1.9 mg·kg−1·day−1) and rapid pacing, 4) concomitant combined ATRA (TCV116, 0.75 mg·kg−1·day−1) and ACEI (enalapril 0.95 mg·kg−1·day−1) and rapid pacing, and 5) sham-operated control. Plasma bradykinin levels were increased and B2 receptors were synergistically upregulated in CHF groups treated with combined ATRA and ACEI compared with those treated with ATRA or ACEI alone. HOE-140 (0.3 mg/kg), a bradykinin B2 receptor antagonist, produced an increase in total systemic resistance and a decrease in left ventricular contractility in CHF with combined therapy compared with either monotherapy. Thus, endogenous bradykinin partially contributes to the synergistic improvement of cardiovascular function in CHF with additional treatment with ATRA to ACEI.