Impact of severe coronary disease associated or not associated with diabetes mellitus on outcome of interventional treatment using stents: results from HERZ (Heart Research Group of Kanazawa) analyses.

Percutaneous coronary intervention (PCI) using a drug-eluting stent (DES) leads to less re-stenosis than PCI using a bare metal stent (BMS), however there is still controversy whether use of a DES for severe coronary disease leads to an acceptable outcome in patients with diabetes mellitus (DM). In this study 8159 lesions were treated in 6739 patients (mean age 68.9 years) with coronary artery disease. Use of a DES significantly decreased the re-stenosis rate compared with BMS in both DM (9.6% versus 21.3%) and non-DM (9.5% versus 17.1%) patients. The re-stenosis rate was significantly higher in DM than in non-DM patients in the BMS group but not in the DES group. There was no statistically significant difference in event-free survival after stenting of patients with left main coronary artery (LMCA) disease between the BMS and DES groups. It was concluded that, compared with BMS, DES reduced re-stenosis in patients with DM, however, we advise careful treatment after using DES for severe coronary disease, including LMCA lesions, in patients with DM.

Increased QT dispersion does not reflect the increased regional variation of cardiac sympathetic nervous activity in hypertrophic cardiomyopathy.

BACKGROUND: QT dispersion (QTD) reflects regional variation of ventricular repolarization. However, the relationship between QTD and the regional variation of cardiac sympathetic nerve activity in hypertrophic cardiomyopathy (HCM) is not yet elucidated. METHODS: Cardiac sympathetic nerve activity was evaluated in 25 patients with HCM by iodine 123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy. With planar MIBG imaging, heart and mediastinum ratios (H/M) at early (20 minutes) and delayed (3 hours) acquisition and the washout rate (WR) were calculated. Polar maps of left ventricular myocardium were divided into 20 segments. The SD of early uptake (EU-SD), delayed uptake (DU-SD), and WR (WR-SD) in 20 segments as indices of regional variation were calculated. QT intervals were corrected by use of the Bazett formula. RESULTS: Maximum QTc correlated positively with H/M early, WR, and left ventricular wall thickness (LVWT). Minimum QTc correlated positively with WR and LVWT. Corrected QTD (QTDc) correlated negatively with EU-SD, DU-SD, and WR-SD and positively with the interventricular septal thickness/posterior wall thickness ratio. Stepwise regression analysis revealed that the most powerful determinants for maximum QTc, minimum QTc, and QTDc were WR, LVWT, and EU-SD, respectively. CONCLUSIONS: QTD correlated negatively rather than positively with the regional variability index of cardiac sympathetic nerve activity. These results suggest that increased QTD in patients with HCM may not reflect increased heterogeneity of cardiac sympathetic nerve activity.

Arrhythmias in patients with Brugada-type electrocardiographic findings.

Brugada syndrome is characterized by marked ST-segment elevation in the right precordial leads (Bru-ECG) and is associated with a high risk for sudden death. However, it is unclear whether the arrhythmogenesis is caused by the mechanisms responsible for Bru-ECG. The present study investigated the risk of arrhythmias in patients with Bru-ECG by retrospectively analyzing 30 patients (28 men; mean age, 51+/-14 years) with Bru-ECG. Aborted sudden cardiac death (ventricular fibrillation or syncope) occurred in 9 patients (30%); paroxysmal atrial fibrillation was present in 9 (30%) patients in addition to malignant ventricular arrhythmias, and some type of arrhythmic event (aborted sudden cardiac death or paroxysmal atrial fibrillation) occurred in 15 patients (50%). Of all the arrhythmic events, 93% occurred at night or early in the morning, and 92% had pronounced ST-segment elevation. These results suggest that Bru-ECG may be associated not only with an increased risk of ventricular tachyarrhythmias but also with an increased risk of paroxysmal atrial fibrillation, and that the arrhythmogenesis may be related to the pronounced ST-segment elevation.

Cardiac troponin T Arg92Trp mutation and progression from hypertrophic to dilated cardiomyopathy.

BACKGROUND: Mutations in the cardiac troponin T gene causing familial hypertrophic cardiomyopathy (HCM) are associated with a very poor prognosis but only mild hypertrophy. To date, the serial morphologic changes in patients with HCM linked to cardiac troponin T gene mutations have not been reported. HYPOTHESIS: The aim of this study was to determine the long-term course of patients with familial HCM caused by the cardiac troponin T gene mutation, Arg92Trp. METHODS: In all, 140 probands with familial HCM were screened for mutations in the cardiac troponin T gene. RESULTS: The Arg92Trp missense mutation was present in 10 individuals from two unrelated pedigrees. They exhibited different cardiac morphologies: three had dilated cardiomyopathy-like features, five had asymmetric septal hypertrophy with normal left ventricular systolic function, one had electrocardiographic abnormalities without hypertrophy, and one had the disease-causing mutation but did not fulfill the clinical criteria for the disease. The mean maximum wall thickness was 14.1 +/- 6.0 mm. The three patients with dilated cardiomyopathy-like features had progressive left ventricular dilation. Three individuals underwent right ventricular endomyocardial biopsy. There was a modest degree of myocardial hypertrophy (myocyte diameter: 18.9 +/- 5.2 microm), and minimal myocardial disarray and mild fibrosis were noted. CONCLUSION: The Arg92Trp substitution in the cardiac troponin T gene shows a high degree of penetrance, moderate hypertrophy, and early progression to dilated cardiomyopathy in Japanese patients. Early identification of individuals with this mutation may provide the opportunity to evaluate the efficacy of early therapeutic interventions.

Coronary lesion morphology and prognosis in young males with myocardial infarction with or without familial hypercholesterolemia.

The present study examined the angiographic characteristics and prognosis of young males under 40 years of age with acute myocardial infarction (AMI) and familial hypercholesterolemia (FH). The study group was divided into an FH group (n=16) and a non-FH group (n=27). Lesion morphology was classified as complex or smooth. Overall 36 patients were followed up for an average of 9.4 years. The frequency of angiographic normal or nonobstructive culprit lesions was significantly higher in the non-FH group (p<0.01). In contrast, the incidence of complex or totally occlusive lesions was higher in the FH group (p<0.01). At 10-year follow-up, survival rates from cardiac death (FH 85% vs non-FH 100%, p=0.06), from AMI (FH 43% vs non-FH 80%, p<0.05), and from any ischemic event at a new lesion (FH 9% vs non-FH 67%, p<0.01) were all reduced in the FH group. These results suggest that the mechanism of AMI in young male patients with FH differs from that in similar aged patients without FH, and that the overall prognosis of these patients is less favorable.

Systolic dysfunction and blood pressure responses to supine exercise in patients with hypertrophic cardiomyopathy.

Left ventricular function and blood pressure responses were evaluated in 56 patients with non-obstructive hypertrophic cardiomyopathy (HCM) and 12 control subjects by using a radionuclide ventricular function monitor during supine ergometer exercise. Patients with HCM were divided into 2 groups: (i) group A had no decrease in ejection fraction (EF) during exercise; and (ii) group B had a decrease in EF during exercise. During exercise, the change in end-diastolic volume did not differ between the 3 groups. In contrast, the change in end-systolic volume differed between the 3 groups (p<0.0001). The change in systolic blood pressure (SBP) also differed significantly between the 3 groups. The change in SBP in group B was smaller than that in the control group and group A, and changes in the EF and changes in the SBP between rest and peak exercise showed a significant correlation (p<0.005). These results suggest that exercise-induced systolic dysfunction in patients with non-obstructive HCM may contribute to abnormal blood pressure response in those patients.

Quantitative assessment of diffuse coronary artery disease using a three-dimensional reconstruction method compared with intravascular ultrasound images.

BACKGROUND: It can be difficult to estimate the degree of stenosis in patients with diffuse coronary artery disease (CAD), because of the lack of a normal reference segment. If the size of normal coronary lumen has a direct relation to size of distal myocardial bed, it could be used to estimate the 'normal' cross-sectional area of coronary lumen. Accordingly, we could estimate the degree of stenosis of coronary arteries with diffuse disease by comparing them with calculated 'normal' areas of lumen. OBJECTIVE: To assess the validity of the above hypothesis. METHOD: Fourteen subjects without coronary atherosclerosis (group A) and 16 patients with CAD (group B) underwent simultaneous bidirectional coronary arteriography. Using these coronary arteriograms, we determined the relationship between cross-sectional area of coronary lumen measured by using a computerized edge-detection system and summed distal branch length calculated by using our computerized three-dimensional reconstruction method. RESULTS: For group A, we found a close correlation between area of lumen and branch length (r= 0.948). However, for group B, there were some segments for which the measured area of lumen was clearly smaller than that expected from the relationship for group A. From this relationship for group A, we calculated the stenosis ratios of 22 segments and, to confirm their accuracy, we compared the stenotic ratios with those measured on intravascular ultrasound images. The stenotic ratio of each segment of stenotic coronary artery calculated by our method agreed significantly well with the results obtained from the ultrasound measurements (r= 0.980). CONCLUSIONS: These observations validate a novel approach to quantifying diffuse CAD using clinical arteriograms.

Collagen remodeling and cardiac dysfunction in patients with hypertrophic cardiomyopathy: the significance of type III and VI collagens.

BACKGROUND: The relationship between the extent of myocardial interstitial fibrosis, the percentage of each type of collagen, and cardiac function in patients with hypertrophic cardiomyopathy (HC) has not been established. HYPOTHESIS: The study aimed to establish that increases in some types of collagen may correlate with cardiac dysfunction. METHODS: Mallory-Azan staining and immunohistochemical staining by the avidin-biotin-complex (ABC) method using anticollagen antibodies were performed on the myocardial biopsy specimens in 35 patients with HC, and the percentage and type of collagen present was determined. Left ventricular (LV) function was evaluated by cardiac catheterization and ventriculography. RESULTS: The percentage of myocardial interstitial fibrosis correlated highly with indices of LV diastolic and systolic function. The amount of type III collagen correlated significantly with the peak negative dp/dt, the rapid filling volume/stroke volume, and the ejection fraction (EF). Significant correlations also were noted between the amount of type VI collagen and peak negative dp/dt, peak positive dp/dt, and EF. Type I collagen did not correlate with any of the LV function indices, and type IV collagen correlated only with peak ejection rate. Type V collagen did not accumulate substantially in the myocardial interstitium. CONCLUSIONS: The progression of myocardial interstitial fibrosis in the HC heart adversely impacts both the diastolic and systolic function of the LV. Increases in the percentage of type III and VI collagen correlate with cardiac dysfunction.

Pharmacokinetics of milrinone in patients with congestive heart failure during continuous venovenous hemofiltration.

OBJECTIVE: To evaluate the pharmocokinetics of intravenous milrinone in patients with severe congestive heart failure during continuous venovenous hemofiltration (CVVH). DESIGN: Prospective study of patients with congestive heart failure admitted to the intensive care unit (ICU). SETTING: ICU between September 1997 and August 1999. PATIENTS AND METHODS: Six patients with severe congestive heart failure during CVVH: all patients received a continuous infusion of milrinone of 0.25 microg x kg(-1) min(-1). The hemodynamics and plasma concentration of milrinone were measured before and after the infusion. Pharmacokinetics were analyzed with one-compartment model featuring constant rate infusion. RESULTS: The steady-state concentration (Css) was 845 +/- 135 (mean +/- SD) ng/ml, and the half-life time (t1/2) was 20.1 +/- 3.3 h. Cardiac index and stroke volume index after the infusion of milrinone increased significantly compared with pre-infusion levels. Other hemodynamic parameters did not change significantly. All patients died within 1 month after the injection of milrinone because of severe forms of arrhythmia, such as ventricular tachycardia and ventricular fibrillation. CONCLUSIONS: We found that the mean Css and the mean t1/2 of milrinone in subjects during CVVH were much higher and longer than those previously reported for subjects with normal renal function. It is therefore essential to adjust the dose or modify the dosing interval of milrinone during renal replacement therapy for patients with severe congestive heart failure. However, further studies are needed to determine the details of pharmacokinetics of milrinone and therapeutic procedures for patients with severe heart failure during CVVH.

Identical twins with long QT syndrome associated with a missense mutation in the S4 region of the HERG.

Familial long QT syndrome (LQTS) is caused by mutations in genes encoding ion channels important in determining ventricular repolarization. Mutations in at least five genes have been associated with the LQTS. Fire genes, KCNQ1, HERG, SCN5A, KCNE1, and KCNE2, have been identified. We have identified a missense mutation in the HERG gene in identical twins in a Japanese family with LQTS. The identical twins in our study had QT prolongation and the same missense mutation. However only the proband had a history of syncope. Although many mutations in LQT genes have been reported, there are few reports of twins with LQTS. This is the first report, to our knowledge, of identical twins with a HERG gene mutation.

Left ventricular systolic dysfunction during exercise and dobutamine stress in patients with hypertrophic cardiomyopathy.

OBJECTIVES: We sought to characterize stress-induced left ventricular systolic dysfunction in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Myocardial ischemia and diastolic dysfunction occur in patients with HCM. We hypothesized that, in the setting of transient myocardial ischemia, left ventricular systolic dysfunction occurs during exercise and dobutamine stress. METHODS: We studied 39 patients with HCM but without obstructive symptoms at rest or coronary artery disease. A continuous ventricular function monitor equipped with cadmium telluride detectors (VEST) was used to evaluate left ventricular function during supine bicycle ergometer exercise. Dobutamine stress echocardiography (DSE) was also performed. The left ventricular ejection fraction (LVEF) and regional wall motion were determined from echocardiographic images. RESULTS: Changes in the LVEF correlated between exercise and dobutamine stress (r = 0.643, p < 0.0001). The LVEF decreased more than 5% at peak exercise in 17 of patients (group II), while the other patients had normal responses (group I). New regional wall motion abnormalities during dobutamine infusion were detected in 18 of 110 (16.4%) segments in group I and 42 of 85 (49.4%) segments in group II. Decreased or unchanged regional wall motion occurred more frequently in hypertrophied segments than in nonhypertrophied segments (p < 0.0001). There were significant inverse correlations between the LVEF responses during both stresses and the number of abnormal segments noted during dobutamine stress in all patients (VEST: p < 0.005; DSE: p < 0.0005). Signs of left ventricular obstruction were observed in 11 of 39 patients during DSE. However, there was no significant correlation between the LVEF response and the dobutamine-induced left ventricular pressure gradient. CONCLUSIONS: Exercise-induced systolic dysfunction occurred in 50% of patients with HCM. In these patients, regional wall motion abnormalities were present in hypertrophied segments.

Clinical features of hypertrophic cardiomyopathy caused by a Lys183 deletion mutation in the cardiac troponin I gene.

BACKGROUND: Mutations that cause hypertrophic cardiomyopathy (HCM) have been identified in 9 genes that code proteins in the sarcomere. Previous reports have demonstrated that cardiac troponin I (cTnI) gene mutations may account for familial HCM; however, the clinical characteristics and prognosis of patients with HCM caused by cTnI gene mutations are not known. METHODS AND RESULTS: We analyzed cTnI gene mutations in 130 unrelated probands with HCM and their families to clarify the genotype-phenotype correlations. We identified 25 individuals in 7 families with a Lys183 deletion (Lys183 del) mutation in exon 7 of the cTnI gene. The disease penetrance in subjects aged >20 years was 88% by echocardiography and 96% by ECG. Sudden death occurred in 7 individuals of 4 families at any age. Overall, 7 (43.8%) of 16 individuals aged >40 years had left ventricular systolic dysfunction, and 3 (18.8%) displayed dilated cardiomyopathy-like features. Of affected individuals, 4 of 5 individuals aged >40 years followed by echocardiography showed septal thinning and decreased fractional shortening during >5 years of follow-up. CONCLUSIONS: The Lys183 del mutation in the cTnI gene in patients with HCM is associated with variable clinical features and outcomes. HCM caused by the Lys183 del mutation has a significant disease penetrance. This mutation is associated with sudden death at any age and dilated cardiomyopathy-like features in those aged >40 years. However, it remains unclear whether screening of families with HCM for this mutation will be useful in patient management and counseling.

Cardiac dysfunction and long-term prognosis in patients with nonobstructive hypertrophic cardiomyopathy and abnormal (123)I-15- (p-Iodophenyl)-3(R,S)-methylpentadecanoic acid myocardial scintigraphy.

To evaluate the relationship between myocardial scintigraphic abnormalities based on (123)I-radioiodinated 15-(p-iodophenyl)-3(R, S)-methylpentadecanoic acid (BMIPP) uptake and cardiac function and the relationship between these abnormalities and long-term prognosis in patients with hypertrophic cardiomyopathy (HCM), 27 patients with nonobstructive HCM underwent BMIPP myocardial scintigraphic study, echocardiography, and exercise radionuclide study. Based on the extent of BMIPP scintigraphic defects, the patients were divided into two groups: Group A (n = 19) patients had no or small defects, and group B (n = 8) patients had moderate to large defects. Cardiac events were recorded over an average period of 64 months. The left ventricular end-diastolic and end-systolic dimensions were significantly greater in group B than in group A. The fractional shortening in group B was less than in group A (p = 0.0002). The BMIPP score and fractional shortening at rest correlated significantly (p < 0.05). The BMIPP score and the change in ejection fraction between rest and peak exercise correlated significantly (p < 0.05). While only 1 cardiac event occurred in the 19 patients in group A during a mean follow-up period of 64 months, 6 cardiac events occurred in the 8 patients in group B. The 84-month event-free survival rate was 94.4% in group A and 14.6% in group B (p < 0.01). These results suggest that patients with HCM and moderate to large defects as assessed by BMIPP myocardial scintigraphy have decreased cardiac function and a poor prognosis.

Exercise-induced ST-segment depression and systolic dysfunction in patients with nonobstructive hypertrophic cardiomyopathy.

BACKGROUND: ST-segment depression is common in patients with hypertrophic cardiomyopathy (HCM). However, it is not clear whether exercise-induced ST-segment depression in patients with HCM and patent coronary arteries is associated with changes in left ventricular function. METHODS: Left ventricular function was continuously evaluated in 53 patients with nonobstructive HCM during supine ergometer exercise with a radionuclide ventricular function monitor equipped with a cadmium telluride detector. On the basis of the ST-segment changes during exercise, the patients were divided into 2 groups: group N had no ST-segment depression, and group D had >/=0.1 mV ST-segment depression. RESULTS: Exercise duration, blood pressure, heart rate, and rate-pressure product during exercise did not differ between the 2 groups. End-diastolic volume at rest and at peak exercise did not differ between groups D and N. In contrast, the end-systolic volume in group N decreased during exercise, whereas in group D it increased. As a result, the left ventricular ejection fraction in group D decreased from 70% +/- 7% to 59% +/- 15% (P <.0001), whereas ejection fraction in group N increased from 65% +/- 8% to 71% +/- 11% (P =.0002). There was a strong correlation between exercise-induced ST-segment depression and changes in ejection fraction from rest to peak exercise (P <.0001). CONCLUSIONS: These results suggest that the exercise-induced ST-segment depression seen in patients with nonobstructive HCM is associated with systolic dysfunction during exercise.

Cardiac sympathetic activity in the asymmetrically hypertrophied septum in patients with hypertension or hypertrophic cardiomyopathy.

BACKGROUND: In patients with essential hypertension (HT), proportional (symmetric) left ventricular hypertrophy (LVH) is common. In contrast, hypertrophic cardiomyopathy (HCM) is characterized by disproportional LVH and, in particular, asymmetric septal hypertrophy (ASH); however, some hypertensive patients also develop ASH. It has not been determined whether such cases represent a distinct type of hypertensive LVH or HCM combined with hypertension. HYPOTHESIS: The study was undertaken to evaluate sympathetic activity in the interventricular septum in patients with HT and ASH or in patients with HCM. METHODS: The patients were evaluated by I-123 meta-iodobenzylguanidine (MIBG) and thallium-201 (201Tl) single-photon emission computed tomography (SPECT), respectively. They were divided into three groups: patients with essential HT and symmetric septal hypertrophy (Group A), patients with HT and ASH (Group B), and patients with HCM and ASH (Group C). RESULTS: Compared with the lateral wall, early uptake of MIBG in the septum was significantly higher in Group B than in Group A, but not significantly different between Groups A and C. Compared with the lateral wall, early uptake of 201Tl in the septum did not differ among the three groups. No significant difference in the MIBG clearance in the lateral wall was seen among the three groups. By contrast, MIBG clearances in the septum and apex were significantly greater in Group C than in Groups A and B. There was an inverse correlation between systolic thickening and MIBG clearance in the septum. CONCLUSION: These findings suggest that sympathetic activity in the septum differs between patients with HT and ASH and patients with HCM.

Diagnostic usefulness of the post-exercise systolic blood pressure response for the detection of coronary artery disease in patients with diabetes mellitus.

Patients with diabetes mellitus (DM) often have a positive result on exercise testing despite a normal coronary arteriogram, which indicates that exercise-induced ST depression is not always an accurate indicator of the presence of coronary artery disease (CAD) in such patients. The present study evaluated the usefulness of the post-exercise systolic blood pressure (SBP) response for the detection of CAD in 47 consecutive patients with DM. Significant stenotic lesions were detected by angiography in 25 patients; 18 of these had true positive (TP) exercise testing results, and 7 had false negative (FN) results. No significant stenotic lesions were detected in the remaining 22 patients and of these 10 had true negative (TN) exercise testing results, and 12 had false positive (FP) results. The SBP ratio (SBP after 3 min of recovery divided by the SBP at peak exercise) was significantly higher in patients with coronary stenoses than in those without. Analysis of the relative cumulative frequency revealed that a SBP ratio greater than 0.87 was associated with significant stenoses. The sensitivity, specificity, and accuracy of ST change combined with a SBP ratio greater than 0.87 for detecting stenoses in patients with DM were 68%, 82%, and 74%, respectively. These results suggest that calculating the SBP ratio, in combination with monitoring for ST depression, improves the accuracy of treadmill exercise testing for the detection of CAD in patients with DM.

[A quantitative evaluation of coronary steal phenomenon in coronary artery-pulmonary artery fistula: case report].

A 67-year-old woman was admitted to our hospital with a complaint of anterior chest pain on exertion. Auscultation disclosed a continuous murmur and exercise electrocardiography revealed positive ischemic ST change. Coronary angiography showed a large left coronary fistula and a small right coronary fistula into the main pulmonary artery. To evaluate the influence of the fistula on coronary circulation, we measured blood flow in the left anterior descending artery (LAD) and in the fistula artery using a 0.014 inch Doppler guide wire. Before surgery, blood flow in the LAD decreased during rapid atrial pacing (130 bpm) but that in the fistula remained constant. After the surgery, there was no remarkable decrease in blood flow in the LAD during rapid atrial pacing (130 bpm), and the preoperative reduction ratio was calculated as 24% compared with postoperatively. These findings suggest that coronary steal phenomenon was involved in myocardial ischemia in this patient.

Severe hypercalcemia and polyuria in a near-drowning victim.

A 73-year-old man was admitted because of near-drowning in a hot springs bath. Transient severe hypercalcemia and polyuria were seen during the first hospital day. It seemed that the hypercalcemia was due to acute intoxication from calcium contained in the water of the spring absorbed mainly through the alveoli. To our knowledge, this is the first case of acute hypercalcemia complicating a near-drowning in a hot spring. Analysis of serum and urine electrolytes during the polyuric phase revealed saline diuresis, which was probably due to interference by the hypercalcemia of the reabsorption of sodium and free water.