Clinical importance of detecting exaggerated blood pressure response to exercise on antihypertensive therapy.

OBJECTIVE: In patients with hypertension, regression of left ventricular hypertrophy (LVH) is associated with improved prognosis. Impact of exaggerated blood pressure response to exercise (Ex-BP) seen in patients with hypertension undergoing antihypertensive therapy on the regression of LVH has not been evaluated. This prospective study investigated the relationship between Ex-BP on antihypertensive therapy and the regression of LVH. METHODS: We prospectively studied 124 never-treated patients with hypertension with LVH. After a pretreatment evaluation, antihypertensive treatment was started and exercise test was performed in all patients. Patients with Ex-BP were divided into the Ex-BP (+) group and those without were divided into the Ex-BP (-) group. Regression of LVH over the follow-up period was compared between the groups. RESULTS: The follow-up duration was approximately 12 months in both the groups. Mean values of blood pressure at rest during the follow-up period were similar between the groups. Reduction of LVH was seen in both the groups. The magnitude of reduction of LVH was significantly smaller in the Ex-BP (+) group compared with the Ex-BP (-) group. Regression of LVH was much frequently seen in the Ex-BP (+) group compared with the Ex-BP (-) group. Multiple regression analysis determined that on-treatment Ex-BP was an independent negative determinant of antihypertensive treatment-induced reduction of LVH. CONCLUSIONS: This study suggests that on-treatment Ex-BP is associated with depressed regression of LVH in patients with hypertension with antihypertensive treatment. If Ex-BP is detected despite receiving antihypertensive agents, improvement of Ex-BP may be necessary to achieve an effective reduction of LVH. Active search of Ex-BP is recommended in patients with hypertension with antihypertensive treatment.

Major non-cardiac surgery is a risk factor for rapid hemodynamic progression of non-rheumatic aortic stenosis.

BACKGROUND: Inflammatory processes are suggested to play a pathogenic role in the development and progression of non-rheumatic aortic stenosis (AS). Major surgery causes an inflammatory reaction. With the increasing prevalence of non-rheumatic AS, the number of affected patients undergoing major surgery increases. We hypothesized that major non-cardiac surgery (MNCS) could accelerate the progression of non-rheumatic AS. METHODS AND RESULTS: We enrolled 218 consecutive patients with non-rheumatic AS who underwent transthoracic echocardiography (TTE) at least twice more than 6 months apart. Study patients were divided into the MNCS group and the non-MNCS group. The MNCS group consisted of patients who underwent MNCS during the TTE follow-up interval. At baseline, peak pressure gradient across the aortic valve (AVG) was similar between the groups. Also baseline clinical characteristics and TTE follow-up interval were similar. The annual rate of peak AVG increase was much higher in the MNCS group than in the non-MNCS group. The proportion of patients with rapid hemodynamic progression was much higher in the MNCS group than in the non-MNCS group. Multiple logistic regression analysis showed that MNCS was an independent predictor of rapid hemodynamic progression of non-rheumatic AS. CONCLUSIONS: The present study indicates for the first time that MNCS is associated with the rapid progression of non-rheumatic AS.

Detection of latent anthracycline-induced cardiotoxicity using left ventricular end-systolic wall stress-velocity of circumferential fiber-shortening relationship.

Although cardiotoxicity is a well-known side effect of anthracycline, detection of subclinical impairment of myocardial contractility at the latent stage is difficult. The left ventricular end-systolic wall stress (WS)-velocity of circumferential fiber-shortening (VCF) relationship reflects the load-independent myocardial contractility and can detect sensitively intrinsic abnormalities in myocardial contractility. Usefulness of this relationship in detecting subclinical anthracycline-induced cardiotoxicity has not yet been established. We investigated whether latent anthracycline-induced cardiotoxicity at the subclinical state can be detected by using the WS-VCF relationship in patients receiving anthracycline therapy. We studied 45 patients who had received anthracycline therapy and 40 healthy controls. All patients had preserved left ventricular ejection fraction (LVEF). WS and VCF were measured using echocardiography. VCF was corrected by heart rate. The WS-VCF relationship was derived by linear regression. Patients with data points lying below -2 SD derived from controls were regarded as having impaired intrinsic myocardial contractility. Although VCF was within normal limits in all patients, it was significantly reduced in the patient group overall compared with the control group. On the other hand, WS was significantly increased in the patient group overall compared with the control group. The WS-VCF relationship demonstrated impaired intrinsic myocardial contractility in 24 patients (53.3 %). In more than half of patients with preserved LVEF, impairment of intrinsic myocardial contractility was detected using the WS-VCF relationship, suggesting the presence of latent anthracycline-induced cardiotoxicity. The WS-VCF relationship may be able to detect sensitively latent anthracycline-induced cardiotoxicity at the subclinical stage.

[An attempt to classify patients with dementia by detrended fluctuation analysis of electroencephalographic data --a preliminary study].

We investigated changes of the scaling exponent alpha estimated by detrended fluctuation analysis (DFA) of electroencephalograms (EEG) in patients with dementia including Alzheimer's disease(AD), and attempted to apply a method of pattern recognition using the alpha value-based feature vector to classify dementia. In 9 patients with AD, 8 patients with other types of dementia (vD), and 7 patients without dementia(C), DFA was performed for approximately one minute with background EEG data recorded at 16 different scalp monopoles. The alpha values were significantly higher in patients with AD at electrodes F7, C3, P3, P4, T3, and T5 than in patients without dementia. No significant difference in alpha values was found between patients with vD and without dementia. Then, an artificial neural network (ANN) was trained on the alpha value-based feature vector of EEG to classify patients with dementia into AD and vD. The trained ANN successfully diagnosed all four new test cases of AD. From these observations, it is suggested that AD has a specific pattern in the alpha value-based feature vector. Thus, pattern recognition using alpha value-based feature vector may be useful for the classification of dementia.

Optimal antihypertensive level for improvement of coronary microvascular dysfunction: the lower, the better?

Recently, coronary microvascular function was documented to be impaired even in patients with prehypertension. However, the impact of antihypertensive level on improvement of coronary microvascular dysfunction in hypertensive patients remains to be established. We investigated the optimal blood pressure achieved with treatment of antihypertensive agents for improvement of coronary microvascular dysfunction in hypertensive patients. We prospectively studied 108 untreated hypertensive patients. All patients were treated with antihypertensive agents for approximately 12 months. Coronary flow reserve (CFR) was measured before and after treatment. The patients were divided into hypertensive, prehypertensive, and normal groups based on their average blood pressure during the treatment period. Pretreatment CFR was similar among all groups. CFR increased significantly in the normal group during the treatment period, but decreased significantly in the prehypertensive and hypertensive groups. This decrease was significantly greater in the hypertensive group than in the prehypertensive group. Multivariate analysis showed lowering blood pressure to normal level to be an independent determinant of improvement in CFR. The normal group was divided into normal-higher and normal-lower subgroups based on their average diastolic blood pressure during the treatment period. Increase in CFR was significantly greater in the normal-higher group than in the normal-lower group. These findings indicate that lowering blood pressure to a normal level is necessary to improve coronary microvascular dysfunction in hypertensive patients. Furthermore, raising diastolic blood pressure to a higher level within normal range has the most beneficial effect. However, as this study is based on observational design, it may have several limitations.

Selective deficit of divided attention following traumatic brain injury: case reports.

Divided attention (DA) impairment may be the most salient and commonly reported cognitive dysfunction following traumatic brain injury (TBI). Even so, DA impairment is sometimes overlooked during hospitalization. Our group experienced two TBI patients with selective deficits of DA recognized after their return-to-work. Neither patient showed abnormalities in standard tests for higher brain dysfunction. Both, however, performed poorly in a newly developed dual-task test. DA should be assessed more thoroughly and carefully in TBI patients. Dual-task testing may be sensitive in the detection of DA disturbances.

Giant left atrial myxoma causing severe pulmonary hypertension.

This report describes a case of giant left atrial myxoma in a 43-year-old woman. She presented with general malaise and dyspnea. Electrocardiogram showed severe right-axis deviation. Transthoracic echocardiography demonstrated a giant mobile mass with size of 6.5 × 4.5 cm in the left atrium. This mass protruded into the left ventricle in diastole and disturbed transmitral left ventricular filling flow. Bilateral atrium and right ventricle were dilated. Severe tricuspid regurgitation was demonstrated with peak pressure gradient of 91 mmHg. This mass was surgically excised and was diagnosed as benign atrial myxoma by histological analysis. Pulmonary hypertension was improved after surgery.

Increase in male fetal deaths in Japan and congenital anomalies of the kidney and urinary tract.

The male to female (M/F) fetal death ratio in Japan from the mid 1970s to 2005s has consistently increased while total fetal deaths have declined. Public health records and other evidence were reviewed to assess the recent trends in infant renal failure, the congenital anomalies of the kidney and urinary tract (CAKUT), and the sex ratio of these disorders. The M/F infant death ratio caused by renal failure has increased from 0.75 to 3.0 over the past 3 decades. There has been an increase in CAKUT as a cause for fetal and infant deaths, and renal hypoplasia and dysplasia were male predominant. The increase in the M/F deaths ratio caused by infant renal failure, as well as increased male predominant CAKUT suggests that the Wolffian duct regression might have affected the initial development of the kidney and male genital tract thus contributing to male fetal deaths.

Exercise-induced delayed onset of left ventricular early relaxation in association with coronary microcirculatory dysfunction in patients with diabetes mellitus.

BACKGROUND: The initiation of ventricular diastole is an energy-dependent phase of cardiac cycle. Delayed onset of left ventricular (LV) relaxation has been proposed to identify myocardial ischemia. Diabetes mellitus (DM) is known to be associated with coronary microangiopathy, but its influence on LV early relaxation is not established. METHODS AND RESULTS: Ninety-two subjects consisting of 70 DM patients without overt cardiac disease and 22 normal controls were evaluated. Using strain rate imaging, time from R-wave on the electrocardiogram to onset of LV relaxation (Tr) was measured at rest and peak exercise. Using myocardial contrast echocardiography, myocardial blood flow (MBF) was measured at rest and peak exercise, enabling MBF reserve. Tr at rest was similar between DM patients and controls, but Tr at peak exercise was significantly longer in DM patients than controls. MBF reserve was significantly reduced in DM patients compared with controls. There was a significant negative correlation between Tr at peak exercise and MBF reserve. In a multivariate analysis, MBF reserve was an independent determinant of Tr at peak exercise. CONCLUSIONS: This study demonstrates that DM patients have exercise-induced delayed onset of LV relaxation in association with impaired coronary microcirculatory function in the absence of coexistent heart disease.

Cardiac Raynaud's phenomenon induced by cold provocation as a predictor of long-term left ventricular dysfunction and remodelling in systemic sclerosis: 7-year follow-up study.

AIMS: The clinical importance of cold-induced reversible myocardial ischaemia, known as cardiac Raynaud's phenomenon (C-Raynaud), has not been established in systemic sclerosis (SSc). This prospective study investigated the impact of C-Raynaud on long-term irreversible left ventricular (LV) functional and morphologic deterioration in SSc. METHODS AND RESULTS: Fifty-one SSc patients with no clinical evidence of cardiac involvement were prospectively followed up for 7.1 +/- 2.2 years. Systolic LV dysfunction was defined as a LV ejection fraction <50%. Left ventricular remodelling was defined as an increase in LV volume during follow-up of more than 20% compared with baseline values. At the initial evaluation, C-Raynaud was found in 15 patients (29.4%). Of these, eight patients had severe C-Raynaud. None of the patients had systolic LV dysfunction. At the final evaluation, five patients had developed systolic LV dysfunction. In four of these five patients, the development of systolic LV dysfunction was associated with LV remodelling. At multivariate analysis, severe C-Raynaud was a strong independent determinant of the development of long-term systolic LV dysfunction. CONCLUSION: This study documents for the first time that severe C-Raynaud is a strong long-term predictor of systolic LV dysfunction in SSc patients. Detection of C-Raynaud is clinically important for identifying SSc patients at high risk of cardiac deterioration at latent stage.

Accessory mitral valve in an elderly man on maintenance hemodialysis.

This report describes a case of accessory mitral valve in an elderly patient on maintenance hemodialysis. Transesophageal echocardiography revealed a mobile sac-like structure with size of 12 × 10 mm(2), which attached to the left ventricular surface of base of the anterior mitral valve leaflet. Mobile stick-like structure with diameter of 21 mm was extending from this sac-like structure toward the left ventricular outflow tract and had a floating free edge. Peak pressure gradient across the left ventricular outflow tract was 32 mmHg. There were no other congenital cardiac anomalies. No clinical findings suggestive of bacterial or nonbacterial vegetation were seen. Also other possibilities of mobile thrombus or calcification were unlikely. These abnormal structures were diagnosed as accessory mitral valve with rudimentary chordae.

Influence of living style and situation on the compliance of taking antihypertensive agents in patients with essential hypertension.

BACKGROUND: As the reason for insufficient control of blood pressure (BP), poor compliance of taking antihypertensive agents is an important issue. In Japan, no prospective study on the compliance of antihypertensive agents has been done. In this study we prospectively investigated the details of the relationship between the compliance of taking antihypertensive agents and living style and situation in hypertensive patients. METHODS: We prospectively examined 121 outpatients with essential hypertension treated with antihypertensive agents for 12 months. Using an oral interview based on the questionnaire sheet, the factors about living style and situations which worsen the compliance were assessed. Also we evaluated the relationship of BP control and season, which was compared between patients with poor compliance and those with good compliance. RESULTS: As for the background of the poor compliance, many factors related to the patients' living style and situation were clarified. On average for 12 months the levels of the compliance and BP showed a significant negative correlation and BP was significantly higher in patients with poor compliance than those with good compliance. However, in the summer season BP did not differ between patients with poor and good compliance, CONCLUSION: Many factors regarding the patients' living style and situation were related to poor compliance. The development of strategy that changes these factors is a future task for improving compliance. This study may also imply that unnecessary antihypertensive agents are prescribed in some patients with poor compliance in the summer season. Determination of the suitable prescription by which to attain optimal individual patients' compliance is important in the treatment of hypertensive patients.

Non-invasive quantitation of myocardial fibrosis using combined tissue harmonic imaging and integrated backscatter analysis in dilated cardiomyopathy.

BACKGROUND: Echocardiographic modalities have challenged the myocardial tissue characterization, but this reliability has not reached to the clinical use. This study investigated whether combined tissue harmonic imaging (THI) and integrated backscatter analysis (IB) provide the reliable and quantitative information about myocardial fibrosis in idiopathic dilated cardiomyopathy (DCM) in comparison with myocardial biopsy findings. METHODS: We studied 56 patients with DCM. All patients underwent left ventricular endomyocardial biopsy and IB with fundamental imaging (FI) and THI. RESULTS: In patients with good echocardiographic image quality, excellent correlations between the percentage of area occupied by myocardial fibrosis (% fibrosis) and the mean of integrated backscatter during a cardiac cycle (m-IB) measured with FI or THI were seen, and the correlation was closer with THI compared with FI. While in patients with poor image quality the correlation between m-IB and % fibrosis was only modest with FI, but the correlation was excellent with THI. Four cut-off values of m-IB with THI obtained from receiver operating characteristic curve discriminated between % fibrosis of more and less than 25, 30, 35, and 40% with high sensitivity and specificity. Multivariate analysis revealed that m-IB with THI was an independent predictor for discrimination of the severity of myocardial fibrosis. CONCLUSION: Combined IB and THI are a clinically applicable method and may be an alternative to myocardial biopsy in evaluating quantitatively myocardial fibrosis in DCM.

Clinical application of wave intensity for the treatment of essential hypertension.

Wave intensity analysis is a method of studying intravascular flow wave propagation, calculated as the product of the rate of change in pressure (d P/ t) and the rate of change in velocity (d U/d t). The typical pattern of wave intensity seen during the cardiac cycle has two dominant peaks. The larger first peak (FP) occurs during early systole when a forward traveling compression wave is generated by the left ventricle. The second smaller peak (SP) follows a period of relatively little net wave production during mid-systole. Wave reflection is seen as a small backward-traveling compression wave occurring just after the first peak of wave intensity (NP). In this study, we investigated the usefulness of parameters from the wave intensity for estimating the efficacy of the Alpha-1 blocker, doxazosin, to reduce blood pressure, by the reduction of peripheral vascular resistance. We examined 20 patients with essential hypertension. Patients were included if their diastolic blood pressure was >95 mmHg on at least three separate visits to the clinic. The study consisted of a 2-week baseline phase followed by a 2-4-week dose-adjusted phase with doxazosin. Treatment began with 1 mg/day doxazosin, and the dose was doubled fortnightly until the diastolic blood pressure was <90 mmHg. Blood-pressure measurements and side effects were recorded at intervals of 2 weeks. Before and after 4 weeks of stable treatment with doxazosin, a comprehensive clinical evaluation was given. Doxazosin reduced systolic and diastolic blood pressure. Both FP and SP increased and NP decreased. DeltaMBP (change in mean blood pressure) correlated well with NP before and after the antihypertensive therapy. The efficacy of doxazosin was confirmed by the decreased reflection wave of aortic flow from wave intensity analysis. Thus, patients with a significant reflection wave may be good candidates for antihypertensive treatment by a vasodilator, such as doxazosin.

[Intravenous myocardial contrast echocardiography; recent advances].

Until quite recently, contrast echocardiography for myocardial perfusion imaging has required the invasive direct injection of contrast agent into the coronary artery. Recent advances in ultrasonic technology and contrast agents have enabled myocardial contrast echocardiography with intra-venous injection of contrast agent in the clinical setting. This noninvasive technique has made the following clinical applications; left ventricular opacification, determination of the endocardium, enhancement of the Doppler flow signals, and detection of myocardial perfusion. Furthermore, in the near future, local drug delivery and pathology-specific targeted adherence of contrast agent may be added to the applications for the treatment. Intravenous myocardial contrast echocardiography is expected to have wide-ranging clinical potential.