Renoprotective effects of telmisartan in patients with advanced chronic kidney disease.

BACKGROUND: Angiotensin II receptor blockers (ARBs) provide renoprotective effects in patients with mild-to-moderate chronic kidney disease (CKD). However, there have been few reports regarding whether ARBs show clinical efficacy and safety in patients with advanced CKD. METHODS: Seventy-two hypertensive patients with Stages 3 - 4 CKD receiving no ARBs were enrolled in this study and observed up to 48 months. Telmisartan was added to conventional antihypertensive agents (n = 36, mean estimated glomerular filtration ratio [eGFR] 19.7 ml/min/1.73 m2) whilst the remaining control patients were not treated with ARBs (n = 36, mean eGFR 19.2 ml/min/1.73 m2). Urinary protein excretion, kidney function, and the occurrence of end-stage renal disease requiring renal replacement therapy, hyperkalemia, and death were analyzed. RESULTS: Baseline characteristics of each group were similar. During the observation period, the blood pressures of each group decreased at similar rates. In the telmisartan group, 17 patients (47.2%) were introduced to renal replacement therapy, as compared with 31 patients (86.1%) in the control group (relative risk 0.55, 95% confidence interval 0.19 - 0.92, p < 0.05). Telmisartan significantly reduced proteinuria levels (from 3.47 +/- 3.00 to 2.41 +/- 2.46 g/g . creatinine, p < 0.05) and was associated with a reduction of 49.6% in the decline rate of eGFR. The incidence of major adverse events in both groups was similar. CONCLUSIONS: The addition of telmisartan to conventional antihypertensive therapy is associated with significant improvement in kidney outcome without increased incidence of adverse effects, even in patients with advanced CKD.

Clock and ATF4 transcription system regulates drug resistance in human cancer cell lines.

The mechanisms underlying cellular drug resistance have been extensively studied, but little is known about its regulation. We have previously reported that activating transcription factor 4 (ATF4) is upregulated in cisplatin-resistant cells and plays a role in cisplatin resistance. Here, we find out a novel relationship between the circadian transcription factor Clock and drug resistance. Clock drives the periodical expression of many genes that regulate hormone release, cell division, sleep-awake cycle and tumor growth. We demonstrate that ATF4 is a direct target of Clock, and that Clock is overexpressed in cisplatin-resistant cells. Furthermore, Clock expression significantly correlates with cisplatin sensitivity, and that the downregulation of either Clock or ATF4 confers sensitivity of A549 cells to cisplatin and etoposide. Notably, ATF4-overexpressing cells show multidrug resistance and marked elevation of intracellular glutathione. The microarray study reveals that genes for glutathione metabolism are generally downregulated by the knockdown of ATF4 expression. These results suggest that the Clock and ATF4 transcription system might play an important role in multidrug resistance through glutathione-dependent redox system, and also indicate that physiological potentials of Clock-controlled redox system might be important to better understand the oxidative stress-associated disorders including cancer and systemic chronotherapy.

Coexistence of hERG current block and disruption of protein trafficking in ketoconazole-induced long QT syndrome.

BACKGROUND AND PURPOSE: Many drugs associated with acquired long QT syndrome (LQTS) directly block human ether-a-go-go-related gene (hERG) K(+) channels. Recently, disrupted trafficking of the hERG channel protein was proposed as a new mechanism underlying LQTS, but whether this defect coexists with the hERG current block remains unclear. This study investigated how ketoconazole, a direct hERG current inhibitor, affects the trafficking of hERG channel protein. EXPERIMENTAL APPROACH: Wild-type hERG and SCN5A/hNa(v) 1.5 Na(+) channels or the Y652A and F656C mutated forms of the hERG were stably expressed in HEK293 cells. The K(+) and Na(+) currents were recorded in these cells by using the whole-cell patch-clamp technique (23 degrees C). Protein trafficking of the hERG was evaluated by Western blot analysis and flow cytometry. KEY RESULTS: Ketoconazole directly blocked the hERG channel current and reduced the amount of hERG channel protein trafficked to the cell surface in a concentration-dependent manner. Current density of the hERG channels but not of the hNa(v) 1.5 channels was reduced after 48 h of incubation with ketoconazole, with preservation of the acute direct effect on hERG current. Mutations in drug-binding sites (F656C or Y652A) of the hERG channel significantly attenuated the hERG current blockade by ketoconazole, but did not affect the disruption of trafficking. CONCLUSIONS AND IMPLICATIONS: Our findings indicate that ketoconazole might cause acquired LQTS via a direct inhibition of current through the hERG channel and by disrupting hERG protein trafficking within therapeutic concentrations. These findings should be considered when evaluating new drugs.

Design of a new surgical approach for ventricular remodeling to relieve ischemic mitral regurgitation: insights from 3-dimensional echocardiography.

BACKGROUND: Mechanistic insights from 3D echocardiography (echo) can guide therapy. In particular, ischemic mitral regurgitation (MR) is difficult to repair, often persisting despite annular reduction. We hypothesized that (1) in a chronic infarct model of progressive MR, regurgitation parallels 3D changes in the geometry of mitral leaflet attachments, causing increased leaflet tethering and restricting closure; therefore, (2) MR can be reduced by restoring tethering geometry toward normal, using a new ventricular remodeling approach based on 3D echo findings. METHODS AND RESULTS: We studied 10 sheep by 3D echo just after circumflex marginal ligation and 8 weeks later. MR, at first absent, became moderate as the left ventricle (LV) dilated and the papillary muscles shifted posteriorly and mediolaterally, increasing the leaflet tethering distance from papillary muscle tips to the anterior mitral annulus (P<0.0001). To counteract these shifts, the LV was remodeled by plication of the infarct region to reduce myocardial bulging, without muscle excision or cardiopulmonary bypass. Immediately and up to 2 months after plication, MR was reduced to trace-to-mild as tethering distance was decreased (P<0.0001). LV ejection fraction, global LV end-systolic volume, and mitral annular area were relatively unchanged. By multiple regression, the only independent predictor of MR was tethering distance (r(2)=0.81). CONCLUSIONS: Ischemic MR in this model relates strongly to changes in 3D mitral leaflet attachment geometry. These insights from quantitative 3D echo allowed us to design an effective LV remodeling approach to reduce MR by relieving tethering.

Mechanism of dynamic regurgitant orifice area variation in functional mitral regurgitation: physiologic insights from the proximal flow convergence technique.

OBJECTIVES: We used the Doppler proximal flow convergence technique as a physiologic tool to explore the effects of the time courses of mitral annular area and transmitral pressure on dynamic changes in regurgitant orifice area. BACKGROUND: In functional mitral regurgitation (MR), regurgitant flow rate and orifice area display a unique pattern, with peaks in early and late systole and a midsystolic decrease. Phasic changes in both mitral annular area and the transmitral pressure acting to close the leaflets, which equals left ventricular-left atrial pressure, have been proposed to explain this dynamic pattern. METHODS: In 30 patients with functional MR, regurgitant orifice area was obtained as flow (from M-mode proximal flow convergence traces) divided by orifice velocity (v) from the continuous wave Doppler trace of MR, transmitral pressure as 4v(2), and mitral annular area from two apical diameters. RESULTS: All patients had midsystolic decreases in regurgitant orifice area that mirrored increases in transmitral pressure, while mitral annular area changed more gradually. By stepwise multiple regression analysis, both mitral annular area and transmitral pressure significantly affected regurgitant orifice area; however, transmitral pressure made a stronger contribution (r2 = 0.441) than mitral annular area (added r2 = 0.008). Similarly, the rate of change of regurgitant orifice area more strongly related to that of transmitral pressure (r2 = 0.638) than to that of mitral annular area (added r2 = 0.003). A similar regurgitant orifice area time course was observed in four patients with fixed mitral annuli due to Carpentier ring insertion. CONCLUSIONS: In summary, the time course and rate of change of regurgitant orifice area in patients with functional MR are predominantly determined by dynamic changes in the transmitral pressure acting to close the valve. Thus, although mitral annular area helps determine the potential for MR, transmitral pressure appears important in driving the leaflets toward closure, and would be of value to consider in interventions aimed at reducing the severity of MR.

Two-dimensional echocardiographic assessment of papillary muscle contractility in patients with prior myocardial infarction.

OBJECTIVES: This study was performed to assess the length and contractile performance of human left ventricular papillary muscles and to determine the relation between papillary muscle dysfunction and mitral regurgitation. BACKGROUND: Assessment of human papillary muscle contractility remains a clinical challenge. METHODS: Two-dimensional echocardiographic examinations were performed in 16 normal subjects and 31 patients with prior myocardial infarction. Apical echocardiograms were used to obtain long-axis views of the anterior and posterior papillary muscles. The end-systolic and end-diastolic lengths of the papillary muscles were measured and fractional shortening was calculated. RESULTS: Fractional shortening in normal subjects was 27 +/- 8% for the anterior papillary muscle and 30 +/- 8% for the posterior papillary muscle. In patients with prior myocardial infarction, a significant decrease in fractional shortening was observed in proportion to the severity of left ventricular wall motion abnormalities at the site of papillary muscle implantation. Moderate or severe mitral regurgitation was significantly more frequent in patients with combined anterior and posterior papillary muscle dysfunction than in those with isolated anterior or posterior dysfunction or with normal function of both papillary muscles (p < 0.05). CONCLUSIONS: Two-dimensional echocardiography is useful for demonstrating abnormal contractility of human left ventricular papillary muscles. Papillary muscle contractility should be analyzed in each case to elucidate the mechanism of mitral regurgitation in patients with papillary muscle dysfunction.

Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: evidence for increased valve tethering.

OBJECTIVES: We tested the hypothesis that patients with incomplete systolic mitral leaflet closure (IMLC: apically displaced coaptation) also have restricted diastolic leaflet opening that is independent of mitral inflow volume and provides evidence supporting increased leaflet tethering. BACKGROUND: Competing hypotheses for functional mitral regurgitation (MR) with IMLC include global left ventricular (LV) dysfunction per se (reduced leaflet closing force) versus geometric distortion of the mitral apparatus by LV dilation (augmented leaflet tethering). These are inseparable in systole, but restricted leaflet motion has also been observed in diastole, and attributed to reduced mitral inflow. METHODS: Diastolic mitral leaflet excursion and orifice area were measured by two-dimensional echocardiography in 58 patients with global LV dysfunction, 36 with and 22 without IMLC, compared with 21 normal subjects. The biplane Simpson's method was used to calculate LV ejection volume, which equals mitral inflow volume in the absence of aortic regurgitation. RESULTS: The diastolic mitral leaflet excursion angle was markedly reduced in patients with IMLC compared with those without IMLC, whose ventricles were smaller, and normal subjects (17 +/- 10 degrees vs. 58 +/- 13 degrees vs. 67 +/- 8 degrees, p < 0.0001). Excursion angle was dissociated from mitral inflow volume (r2 = 0.04); excursion was reduced in patients with IMLC despite a normal inflow volume in the larger ventricles with MR (60 +/- 25 vs. 61 +/- 12 ml in normal subjects, p = NS), and excursion was nearly normal in patients without IMLC despite reduced inflow volume (40 +/- 10 ml, p < 0.001 vs. normal subjects). The anterior leaflet when maximally open coincided well with the line connecting its attachments to the anterior annulus and papillary muscle tip (angular difference = 3 +/- 7 degrees vs. 25 +/- 9 degrees vs. 32 +/- 10 degrees in patients with and without IMLC vs. normal subjects, p < 0.0001). In patients with IMLC, the leaflet tip orifice was smaller in an anteroposterior direction but wider than in the other groups, giving a normal total area (6.8 +/- 1.8 vs. 7.1 +/- 1.2 vs. 6.9 +/- 0.8 cm2, p = NS). CONCLUSIONS: Patients with LV dysfunction and systolic IMLC also have restricted diastolic leaflet excursion that is independent of inflow volume, coincides with the tethering line connecting the annulus and papillary muscle and reflects limitation of anterior motion relative to the posteriorly placed papillary muscles without a decrease in total orifice area. These observations are consistent with increased tethering by displaced mitral leaflet attachments in the dilated ventricles of patients with IMLC that can restrict both diastolic opening and systolic closure.

Mechanism of ischemic mitral regurgitation with segmental left ventricular dysfunction: three-dimensional echocardiographic studies in models of acute and chronic progressive regurgitation.

OBJECTIVES: This study aimed to separate proposed mechanisms for segmental ischemic mitral regurgitation (MR), including left ventricular (LV) dysfunction versus geometric distortion by LV dilation, using models of acute and chronic segmental ischemic LV dysfunction evaluated by three-dimensional (3D) echocardiography. BACKGROUND: Dysfunction and dilation-both mechanisms with practical therapeutic implications-are difficult to separate in patients. METHODS: In seven dogs with acute left circumflex (LCX) coronary ligation, LV expansion was initially restricted and then permitted to occur. In seven sheep with LCX branch ligation, LV expansion was also initially limited but became prominent with remodeling over eight weeks. Three-dimensional echo reconstruction quantified mitral apparatus geometry and MR volume. RESULTS: In the acute model, despite LV dysfunction with ejection fraction = 23 +/- 8%, MR was initially trace with limited LV dilation, but it became moderate with subsequent prominent dilation. In the chronic model, MR was also initially trace, but it became moderate over eight weeks as the LV dilated and changed shape. In both models, the only independent predictor of MR volume was increased tethering distance from the papillary muscles (PMs) to the anterior annulus, especially medial and posterior shift of the ischemic medial PM, measured by 3D reconstruction (r2 = 0.75 and 0.86, respectively). Mitral regurgitation volume did not correlate with LV ejection fraction or dP/dt. CONCLUSIONS: Segmental ischemic LV contractile dysfunction without dilation, even in the PM territory, fails to produce important MR. The development of MR relates strongly to changes in the 3D geometry of the mitral apparatus, with implications for approaches to restore a more favorable configuration.

Repeated thermal therapy improves impaired vascular endothelial function in patients with coronary risk factors.

OBJECTIVES: We sought to determine whether sauna therapy, a thermal vasodilation therapy, improves endothelial function in patients with coronary risk factors such as hypercholesterolemia, hypertension, diabetes mellitus and smoking. BACKGROUND: Exposure to heat is widely used as a traditional therapy in many different cultures. We have recently found that repeated sauna therapy improves endothelial and cardiac function in patients with chronic heart failure. METHODS: Twenty-five men with at least one coronary risk factor (risk group: 38 +/- 7 years) and 10 healthy men without coronary risk factors (control group: 35 +/- 8 years) were enrolled. Patients in the risk group were treated with a 60 degrees C far infrared-ray dry sauna bath for 15 min and then kept in a bed covered with blankets for 30 min once a day for two weeks. To assess endothelial function, brachial artery diameter was measured at rest, during reactive hyperemia (flow-mediated endothelium-dependent dilation [%FMD]), again at rest and after sublingual nitroglycerin administration (endothelium-independent vasodilation [%NTG]) using high-resolution ultrasound. RESULTS: The %FMD was significantly impaired in the risk group compared with the control group (4.0 +/- 1.7% vs. 8.2 +/- 2.7%, p < 0.0001), while %NTG was similar (18.7 +/- 4.2% vs. 20.4 +/- 5.1%). Two weeks of sauna therapy significantly improved %FMD in the risk group (4.0 +/- 1.7% to 5.8 +/- 1.3%, p < 0.001). In contrast, %NTG did not change after two weeks of sauna therapy (18.7 +/- 4.2% to 18.1 +/- 4.1%). CONCLUSIONS: Repeated sauna treatment improves impaired vascular endothelial function in the setting of coronary risk factors, suggesting a therapeutic role for sauna treatment in patients with risk factors for atherosclerosis.

Usefulness of adenosine triphosphate-atropine stress echocardiography for detecting coronary artery stenosis.

There have been few studies on adenosine triphosphate (AT) stress echocardiography. The AT stress test may have fewer adverse effects than the adenosine stress test. The addition of atropine to AT echocardiography may enhance the sensitivity for detection of coronary artery disease (CAD). The purpose of this study was to determine the utility of AT-atropine echocardiography for detection of CAD. The group studied consisted of 112 patients with suspected CAD. Sixty-one patients did not have a history of prior myocardial infarction (group I) and 51 patients did (group II). AT was infused intravenously at 180 microg/kg/min for 14 minutes. Atropine (0.25 mg intravenously, repeated up to maximum total dose of 1 mg) was administered starting after 8 minutes of AT infusion. Ischemic response was defined as new or worsening wall motion abnormality occurring during the infusion. The sensitivity and specificity for detection of CAD were assessed using the representative echocardiograms during single AT infusion and AT-atropine infusion. Sixty-two patients had CAD. Fifty-eight patients (52%) developed minor side effects that resolved promptly. The rate-pressure product (10(3)/mm Hg beats/min) was significantly increased at 12 minutes of infusion (12.4+/-3.2) compared with that at baseline (9.1+/-2.3) and that at 6 minutes of infusion (9.4+/-2.1). The sensitivity for detection of CAD was 45% for AT echocardiography and 74% for AT-atropine echocardiography. The specificity was 94% for AT echocardiography and 90% for AT-atropine echocardiography. The sensitivity and specificity of AT-atropine echocardiography was 78% and 93%, respectively, in group I, and 70% and 86%, respectively, in group II. In conclusion, AT-atropine stress echocardiography seems to be well tolerated, safe, and useful for detection of CAD.

Right ventricular stiffness measured by a new method without volume estimation in coronary artery disease.

This study was designed to measure the right ventricular (RV) stiffness (delta P/ delta V) with a new method without estimating the RV volume itself. RV stiffness has rarely been measured due to the difficulty in estimating the RV volume. Without measuring RV volume itself, stiffness can be determined by measuring its volume change (delta V). Tricuspid filling flow volume, which is the diastolic RV delta V, is measurable by using Doppler echocardiography. Thus, RV stiffness may possibly be obtained from Doppler echocardiography combined with high-fidelity RV pressure. Subjects consisted of 8 controls, 8 patients with angina pectoris, 8 with anterior, 8 with posterior, and 8 with inferior prior myocardial infarction. Tricuspid annular dimension was measured by 2-dimensional echocardiography and the tricuspid annular area was calculated. Velocity-time integral of the tricuspid filling flow during the late diastole was measured by pulsed Doppler echocardiography. Then, the late diastolic RV delta V was obtained as the product of the tricuspid annular area and the integral. The late diastolic RV pressure rise (delta P) was also measured with a micromanometer catheter. The RV elastic chamber stiffness constant ([delta P/ delta V]/P) was obtained by dividing simple stiffness by the mean RV pressure during late diastole. The RV elastic chamber stiffness constant did not significantly differ among controls, patients with angina pectoris, and those with anterior and posterior myocardial infarction (0.0054 +/- 0.0009 vs 0.0057 +/- 0.0018 vs 0.0064 +/- 0.002 vs 0.0052 +/- 0.0019 ml-1). However, it was significantly increased in patients with inferior myocardial infarction (0.010 +/- 0.004 ml-1, p < 0.01 or 0.05) compared with those in the other 4 groups. These results suggest (1) that RV stiffness can be measured with a new method without RV volume estimation, and (2) that this new method is useful in evaluating RV diastolic pathophysiology in patients with coronary artery disease.

Influence of left ventricular filling profile on the effect of atrioventricular synchronous pacing.

We correlated the percentage of atrial contribution to left ventricular filling (percent AC) assessed by Doppler echocardiography with the hemodynamic benefit from atrioventricular synchronous pacing assessed by direct hemodynamic measurements. Subjects comprised 40 patients who underwent electrophysiologic catheterization because of unexplained syncope or bradycardia (< 40 beats/min). Femoral arterial and pulmonary capillary wedge pressure were recorded by catheterization, and cardiac output was measured by thermodilution during temporary atrioventricular synchronous (DDD, 70 beats/min with 150 ms of atrioventricular delay) and ventricular (VVI, 70 beats/min) pacing. Mitral inflow velocity by pulsed-wave Doppler echocardiography was recorded during DDD pacing and percent AC was obtained by calculating the ratio of mitral inflow velocity area during atrial systole to total mitral inflow velocity area during early diastole and atrial systole. The mean arterial pressure and the cardiac output increased significantly (99 +/- 16 mm Hg vs 90 +/- 15 mm Hg, p < 0.001; 4.6 +/- 1.0 L/min vs 3.9 +/- 0.9 L/min, p < 0.001), and the mean pulmonary capillary wedge pressure decreased (7 +/- 4 mm Hg vs 10 +/- 4 mm Hg, p < 0.001) during DDD compared with VVI pacing. A significant positive correlation was observed between the percent AC and the increase in cardiac output (r = 0.58, n = 40, p < 0.01) or the increase in mean arterial pressure (r = 0.62, n = 38, p < 0.01) during DDD pacing. The percent AC did not significantly correlate with the decrease in pulmonary capillary wedge pressure. In conclusion, patients with larger percent AC may receive major benefit from atrioventricular synchronous pacing.

Skin test study of Bancroftian filariasis in Kuroshima Island, Okinawa: a 13-year longitudinal study during a control campaign.

A longitudinal study was performed in an island, endemic for Bancroftian filariasis, by blood survey and skin test from the beginning of a filariasis control campaign in 1967 through 1980. The initial microfilarial rate of 13.2% was successfully reduced to almost 0 by 1970, by the selective administration of diethylcarbamazine to microfilaria positives. The age distribution of skin-test positivity changed year by year, especially in the younger age groups. A marked reduction was seen in the positive rate in the 0- to 9- and 10- to 19-year-old age groups. The change of skin reactivity for all islanders was evaluated, and revealed a gradual decrease in the wheal-size over the observation period.

Myocardial perfusion and wall motion in infarction border zone: assessment by myocardial contrast echocardiography.

Several mechanisms have been proposed to explain the decreased wall motion (WM) at the borders of myocardial infarction (MI). We used myocardial contrast echocardiography (MCE) to investigate the relation of perfusion to WM in infarcted border zones (BZs) 6 weeks after MI in 5 sheep. After quantifying the extent of WM abnormality and the perfusion defect, normal (NL), infarcted, and BZs were defined. Peak intensity after contrast was measured in acoustic units (AU). Radiolabeled microspheres were injected to measure regional blood flow. The heart was stained with 2,3, 5-triphenyltetrazolium chloride (TTC). The perfusion defect on MCE was 33% +/- 7% of the total myocardial area and correlated well with TTC (r = 0.92, P <.03). The BZ was 8% +/- 5% of the total myocardial area. Peak intensity after contrast was decreased in MI compared with BZ and NL (MI: 2.5 +/- 1.9 AU, BZ: 8.0 +/- 3.8 AU, P <.005; NL: 10.2 +/- 6.9 AU, P <.02) and comparable in NL and BZ. The blood flow measured by microspheres was not different in NL and BZ but was decreased in MI (NL: 1.6 mL/g/min, BZ: 1.5 +/- 0.5 mL/g/min, MI: 0.7 +/- 0.5 mL/g/min; P <.0001). In this model of chronic ovine MI, the BZ was small and its perfusion was preserved. These findings support the hypothesis that tethering of normal myocardial segments explains the abnormal wall motion noted at the borders of MI.

Comparison of transthoracic Doppler echocardiography and natriuretic peptides in predicting mean pulmonary capillary wedge pressure in patients with chronic atrial fibrillation.

The purpose of this study was to assess whether transthoracic Doppler echocardiography and serum natriuretic peptide levels could predict mean pulmonary capillary wedge pressure (PCWP) in patients with chronic atrial fibrillation. We examined mitral flow velocity and pulmonary venous flow (PVF) velocity patterns in 32 patients with chronic atrial fibrillation. Plasma A-type and B-type natriuretic peptide (ANP, BNP, respectively) levels in the peripheral vein were measured. Significant correlations were observed between mean PCWP and the following: peak velocity (r = 0.51) and deceleration time (r = -0.65) of the mitral flow; peak velocity (r = 0.64) and deceleration time (r = -0.80) of the PVF; BNP (r = 0.60); and ANP (r = 0.36). Stepwise multiple linear regression analysis selected PVF deceleration time and mitral flow deceleration time as independent predictors of PCWP. A cutoff value of PVF deceleration time of < or =150 ms and a mitral flow deceleration time of < or =100 ms predicted a mean PCWP of > or =18 mm Hg, with a sensitivity of 100% and 80% and a specificity of 96% and 85%, respectively. In conclusion, PVF deceleration time and mitral flow deceleration time obtained from transthoracic Doppler echocardiography are more accurate predictors of mean PCWP than values obtained with natriuretic peptides in patients with chronic atrial fibrillation.

Cardiac involvement in congenital myopathy.

We examined cardiac changes in 8 patients (4 men and 4 women, age 21-43 years) with congenital myopathy proven by skeletal muscle biopsy. Of 8 patients, 4 showed cardiac changes, including 1 with cytoplasmic body myopathy (patient 1), 2 with minimal change myopathy (patients 2 and 3) and 1 with nemaline myopathy (patient 4). Patients 1 and 2 showed left ventricular dilatation with severe global hypokinesis of left ventricular wall. These clinical features were quite similar to those of dilated cardiomyopathy and the patients were in NYHA class 3 or 4. Patient 3 had severe mitral regurgitation with mitral valve prolapse. This patient also had a persistent left superior vena cava and hypoplasia of the aorta, and her cardiac function was in NYHA class 3. Patient 4 showed moderate global left ventricular hypokinesis but the left ventricle was not dilated. This patient also had sino-atrial block and type A Wolff-Parkinson-White syndrome. His cardiac function was NYHA class 1. In conclusion, various types of congenital myopathy are associated with cardiac changes which can result in severe congestive heart failure.

Echocardiographic diagnosis of partial anomalous pulmonary venous connection from right upper lobe to the coronary sinus.

A 36-year-old woman was admitted because of an enlarged right heart. Echocardiographic examination revealed an abnormal vessel connecting to the dilated coronary sinus. The abnormal vessel traveled in the direction from the right axillary to the left epigastric region. Partial anomalous pulmonary venous connection (PAPVC) from the right upper lobe to the coronary sinus was initially considered as a possible diagnosis by echocardiography. At surgery, diagnosis of an isolated PAPVC of the right upper pulmonary vein to the coronary sinus was confirmed.

Phonoechocardiographic identification of chordal snap in hypertrophic cardiomyopathy.

In three patients with hypertrophic cardiomyopathy, a late systolic click following mid systolic murmur was recognized. M-mode and two-dimensional echocardiography showed the presence of systolic anterior motion of the chordae tendineae in all cases. Phonoechocardiographic studies showed that the time of the click always coincided with the endpoint of mild anterior motion of the chordae tendineae. The click was considered to be a chordal snap.

[Clinical study on myocardial imaging with beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid in patients with mitochondrial myopathy].

Myocardial imaging with beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP), a new radiopharmaceutical designed to evaluate myocardial fatty acid metabolism, was performed in 7 patients with mitochondrial myopathy to detect their myocardial damages in comparison with 201Tl myocardial imaging. These patients were divided into 4 chronic progressive external ophthalmoplegia (CPEO) cases, 2 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) cases and 1 myoclonus epilepsy with ragged-red fibers (MERRF). In visual assessment, we observed more myocardial segments with decreased uptake of 123I-BMIPP compared to 201Tl in MELAS cases than in CPEO cases. The mean myocardial uptake of 123I-BMIPP was higher than that of 201Tl in CPEO cases. On the other hand, in MELAS and MERRF cases, the mean myocardial uptake of 123I-BMIPP was lower than that of 201Tl. Abnormal findings suggesting myocardial damages were observed in echocardiogram and/or in electrocardiogram in MELAS and MERRF cases, while no such abnormal findings were observed in CPEO cases. Along with the previously reported experimental result that the impairment of rat myocardial mitochondria decreased myocardial uptake of 125I-BMIPP, these results suggest that 123I-BMIPP may be useful to detect myocardial damages in patients with mitochondrial myopathy.