Association of the R485K polymorphism of the factor V gene with poor response to activated protein C and increased risk of coronary artery disease in the Chinese population.

Inherited predisposition to thrombosis contributes to the initiation and progression of coronary artery disease (CAD). The present study was designed to explore the relationship between genetic variation of coagulation factor V and occurrence of CAD. A total of 141 unrelated patients with CAD and 175 healthy controls were analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) for variation detection in all 25 exons of the factor V gene. Among the study subjects, 55 CAD patients and 73 controls were evaluated at random for response to activated protein C (APC) by Coatest APC resistance test. Polymorphisms in exon 4, 10, 13 and 16 of factor V gene were documented [642G-->T(S156), 1628--> A(R485K), 4070A-->G(H1299R) and 5380G A(V1736M), respectively]. The study also identified a novel polymorphism 327A G in exon 2 which did not alter the amino acid residue. Leiden mutation (R506Q) was not detected in any of our 316 subjects. Among the five polymorphisms, the allele frequency of 1628G--> A was significantly different between the CAD patients and the controls (0.36 vs. 0.21, p < 0.05). Subjects homozygous or heterozygous for the A allele of 1628G-->A polymorphism had lower normalized APC ratios than those with the GG genotype in the CAD group (1.16+/-0.13 and 1.18+/-0.23 vs. 1.36+/-0.33, p <0.05) and in the controls, indicating that A(1628) allele was associated with a poor response to APC. We conclude that the 1628G-->A (R485K) polymorphism of factor V is associated with a poor response to APC and increased risk for CAD.

Identification of a novel missense mutation in the cardiac beta-myosin heavy chain gene in a Chinese patient with sporadic hypertrophic cardiomyopathy.

The exons 13, 16, 21 and 23 of cardiac beta-myosin heavy chain (MHC) gene from 32 Chinese patients with hypertrophic cardiomyopathy were analyzed by the polymerase chain reaction and the DNA single strand conformation polymorphism (PCR-SSCP) procedure. The results showed an altered SSCP in exon 13 of one patient. Sequencing analysis revealed that the patient had a G to T transversion in codon 383, resulting in the substitution of Lys by Asn. The missense mutation was also confirmed by Southern blot hybridization with an allele-specific oligonucleotide probe. Because it was found at a residue highly conserved through evolution, this mutation is likely to be the cause of hypertrophic cardiomyopathy in the patient. Because her parents and child were neither clinically nor genetically affected, it was concluded that the mutation in this patient arose de novo and was not passed to her child. This is the first report of a mutant cardiac beta-MHC gene in the Chinese population. Also, it is a novel missense mutation of the cardiac beta-MHC gene.

[Pharmacokinetics and pharmacodynamics of slow release tablet of diltiazem in hypertensive patients with various renal functions].

Twenty hypertensive patients were equally divided into 2 groups: A) with normal renal function (NRF) and B) with impaired renal function (IRF) according to creatinine clearance, blood urea nitrogen and creatinine levels. The pharmacokinetic and pharmacodynamic effects of diltiazem (Dil, 90 mg, bid x 7 d, p.o.) were studied. The pharmacokinetic parameters in IRF patients (Ka 0.7 +/- 0.2 h-1, T 1/2e 3.7 +/- 0.7 h, Cmax1 45 +/- 4 ng.ml-1, Tmax1 3.1 +/- 0.4 h) did not differ from those in NRF patients (0.7 +/- 0.5 h-1, 4.1 +/- 1.3 h, 41 +/- 5 ng.ml-1 and 3.4 +/- 0.4 h, P > 0.05). Antihypertensive efficacy of Dil in patients with IRF was similar to that in those with NRF, and the hypotensive effect lasted over 24 h. The plasma Dil concentrations were strongly correlated with a decrease in BP in both groups. It was concluded that IRF did not affect the disposition of slow release Dil tablet under a steady state. No dosage adjustment of Dil is necessary in hypertensive patients with IRF.

Prognostic importance of left ventricular diastolic filling velocity profiles in dilated cardiomyopathy.

To determine the prognostic importance of pulsed Doppler-derived left ventricular diastolic filling velocity profiles and the relationship between Doppler variables and clinical functional status, the follow-up outcome of 58 patients with dilated cardiomyopathy and symptoms of left ventricular dysfunction was analysed. During a mean follow-up period of 31.2 +/- 12.8 months, 23 died of either progressive pump failure or sudden death. Peak early filling velocity (E) was higher and late atrial filling velocity (A) lower in nonsurvivors than in survivors. The E/A ratio was higher and the deceleration time (DT) of early diastole shorter in nonsurvivors. The mortality was significantly higher in patients with an E/A ratio > 2 or a DT < 150 ms than in those without. Repeated Doppler echocardiographic examinations in 31 of 35 survivors after intense treatment showed decreased E, increased A, reduced E/A ratio and prolonged DT in 18 patients with clinical functional improvement, whereas these measurements were unaltered in the remaining 13 patients whose functional status was unchanged or deteriorated. This study suggests that pulsed Doppler-derived left ventricular diastolic filling variables may be important predictors of outcome in dilated cardiomyopathy and provide useful measures in observing the effects of therapy during long-term follow-up of the patients.

Relationship between left ventricular end-diastolic compliance and abnormal Doppler mitral filling in patients with coronary artery disease.

Left ventricular end-diastolic compliance (LVEDC) and transmitral flow velocities were measured in 19 patients with coronary artery disease associated with hypertension and 10 normal subjects by LV catheterization and pulsed-Doppler echocardiography. LVEDC was much lower in the patient than in the normal subjects (P less than 0.01). The data showed that abnormal Doppler diastolic function such as elevated late diastolic peak flow velocity (PVA) and decreased LVEDC occurred in the patients at the same time. In addition, the negative correlation of PVA with LVEDC observed in normal controls but not in patients suggested that in patients with impaired diastolic filling, factors other than the decreased LVEDC itself must also participate in the development of diastolic dysfunction.

[Characteristics of left ventricular diastolic function in patients with hypertension].

Left ventricular (LV) diastolic filling was examined by Doppler echocardiography in 239 patients with essential hypertension and 100 normal subjects. The Doppler study showed an inverse correlation between age and early diastolic peak velocity (PVE, r-0.201, P less than 0.05) [and a positive correlation between age and late diastolic peak velocity (PVA, r = 0.202, P less than 0.05) in normal subjects. Isovolumic relaxation time and late diastolic filling time were prolonged, PVA, A/E and Ai elevated, PVE, E/A and Ei/Ai as well as total filling time decreased in patients with hypertension as compared with the values found in the normal subjects (P less than 0.05 to 0.01). The results showed definite impairement of LV diastolic function in hypertensive patients. PVA correlated positively with systolic blood pressure (r = 0.68, P less than 0.01) and modestly with left atrial dimension in the hypertensives. No significant differences were found in FS and EF between the two study populations, indicating that LV filling abnormalities may occur early in patients with hypertension, even at a time when systolic performance has not yet been affected.

Myocardial infarction due to isolated left circumflex or right coronary artery occlusion.

The electrocardiographic (ECG) patterns related to clinical spectrum and angiographic features were assessed in 41 patients with first myocardial infarction due to isolated left circumflex coronary artery (LCX) occlusion, and compared to those in 45 patients with right coronary artery (RCA)-related infarction. The occurrence of inferior Q waves was similar in patients with LCX and RCA occlusion, but lateral Q waves and an abnormal R wave in lead V1 were more frequently seen in patients with LCX-related infarction (46% vs 7% and 51% vs 4%, respectively). Compared with patients with LCX-related infarction without an abnormal R wave in lead V1 and those with RCA occlusion, patients with LCX-related infarction and an abnormal R wave in lead V1 associated with inferior and/or lateral Q waves had larger left ventricular end-diastolic and end-systolic volumes, lower ejection fraction, higher incidence of total occlusion of a dominant LCX without collaterals, and more cardiac events during follow-up. The study suggests that the presence of lateral Q waves and an abnormal R wave in lead V1 after myocardial infarction may be a useful marker of LCX occlusion, and that patients with LCX-related infarction may have different status of left ventricular function depending on the size of circulation and the status of residual flow to the infarct region during LCX occlusion.

[Relationship between electrocardiographic pattern and angiographic findings in inferior myocardial infarction].

The relationship between electrocardiographic pattern and angiographic features was assessed in 86 patients with inferior myocardial infarction. Although the occurrence of inferior Q wave was similar in patients with isolated left circumflex (LCX) or right coronary artery (RCA) occlusion, lateral Q wave and abnormal R wave in lead V1 were more frequent in the former. In patients with LCX-related infarction, abnormal R wave in lead V1 associated with inferior and/or lateral Q waves may indicate left ventricular dysfunction, total occlusion of the LCX without collateral circulation, and high cardiac event rate during longterm follow-up.

Angiographic prediction of cardiac events after first acute transmural myocardial infarction. A prospective study of 108 patients.

108 patients with acute myocardial infarction (MI), aged 70 years or younger, underwent left ventriculography and coronary arteriography (mean one month) after infarction and were followed up for an average period of 22 months (range 5-47 months). The contribution of angiographic variables to a first cardiac event (death, recurrent infarction, coronary artery bypass grafting or congestive heart failure) was evaluated with Kaplan-Meier survival curve analysis and long-rank test. Patients with cardiac events had left ventricular dilation, systolic dysfunction, multivessel coronary disease and lack of residual flow to the infarct region. Multivariate analysis showed that left ventricular end-systolic volume (P less than 0.001), end-diastolic volume (P less than 0.01) and the number of the diseased coronary vessels (P less than 0.05) were of significance in predicting the outcome. This prospective study indicates that in survivors of first acute transmural MI, cardiac catheterization performed one month after infarction can provide additive prognostic information that can be used to stratify risk.

Spontaneous alterations in left ventricular regional wall motion after acute myocardial infarction.

For assessing the relationship between the left ventricular (LV) wall motion abnormalities and the status of residual flow to the infarcted region, the extent of coronary artery disease and one-year outcome, 60 patients with a first transmural, Q-wave myocardial infarction (MI) underwent serial echocardiographic examinations. The abnormal wall motion (AWM) score was calculated, and the cardiac events (death, reinfarction, severe ventricular arrhythmia or congestive heart failure) after discharge were recorded. The AWM score of the infarcted area was higher in patients with total occlusion than in those with subtotal occlusion (anterior MI: 14.6 +/- 2.4 vs 7.2 +/- 2.1; inferior MI: 9.7 +/- 2.1 vs 5.1 +/-1.2, all P less than 0.01). Regional wall motion of the noninfarcted area was preserved in patients with single vessel disease but decreased in those with multivessel disease. In patients who developed cardiac events in follow-up period a higher AWM (16.4 +/- 3.7) was found than in those who did not (8.9 +/- 3.1, P less than 0.05). A score of greater than 13 had a strong prediction of cardiac events after acute MI, with a sensitivity of 81%, specificity of 94% and positive predictive accuracy of 88%.

Beneficial effect of residual flow to the infarct region on left ventricular volume changes after acute myocardial infarction.

To determine the relationship between alterations in left ventricular (LV) volumes and residual flow to the infarct region after myocardial infarction (MI), 57 patients with a first acute transmural MI underwent two-dimensional echocardiography within 48 hours of infarction and after 1 month. A reduction in ST segment elevation by greater than or equal to 35% of the peak value of ST segment elevation within the initial 6 hours was used as an indirect indicator for early reperfusion of the infarct-related artery (IRA). IRA patency and collateral circulation were assessed by coronary arteriography performed at 1 month. LV volumes increased in patients with a persistent ST segment elevation within the initial 6 hours of infarction and in those with a totally occluded IRA without collaterals. However, LV volumes were unchanged in patients with early reperfusion and in those who had subtotally occluded IRA or who had collateral circulation. LV dilation (greater than or equal to 20% increase in end-diastolic volume) occurred less often when early reperfusion and angiographically patent IRA or collateral supply to the infarct zone were present. This prospective study indicates that residual flow to the infarct region may exert a beneficial effect on LV volume changes after acute MI.

[Value of angina pectoris after myocardial infarction in predicting the extent of coronary artery disease].

Clinical, hemodynamic, and angiographic data were examined in 53 patients who underwent catheterization within 6 months of a documented first acute transmural myocardial infarction. The patients were divided according to the presence (23 patients) or absence (30 patients) of angina pectoris 1 month after infarction (group I and group II). Group I patients had more severe coronary artery disease and a greater prevalence of multivessel disease than group II patients. Partial preservation of segmental wall function in group I was related to the presence of collateral vessels. In patients with single vessel disease, the incidence of spontaneous recanalization of the infarct-related artery was higher in group I as compared with that in group II. It is concluded that angina pectoris after myocardial infarction suggests multivessel disease or infarct-related artery recanalization. Coronary arteriography may be advised in order to select adequate therapeutic interventions and improve prognosis in these patients.

Relationship between clinical manifestations and coronary angiographic morphology in patients with coronary artery disease.

To study the relationship between clinical manifestations and coronary anatomy and morphology, coronary angiography was performed in 20 patients with chronic stable angina (Group I), in 18 patients with unstable angina (Group II), and in 20 patients with previous myocardial infarction (Group III). Although the site and extent of coronary artery disease were similar among the three groups, coronary morphology differed considerably, with a concentric lesion occurring in 70% of Group I patients and an eccentric lesion in 62% and 63% of Group II and Group III patients, respectively. The study suggests that coronary lesion morphology may form an anatomic basis in determining clinical manifestations for patients with coronary artery disease. An eccentric coronary stenosis may be useful in identifying high-risk patients.

[Estimation of intracellular free calcium concentration in patients undergoing digitalis treatment and in patients presenting digitalis toxicity].

Delayed afterdepolarizations occur under conditions in which there are large increase in the intracellular Ca and may be considered as one of the important mechanisms for digitalis-induced arrhythmias. Intraplatelet free calcium (Ca2i+) was measured in 25 patients, using the fluorescent indicator Quin-2. The patients included 15 with glycosides treatment (Group A) and 10 with arrhythmias indicating the presence of digitalis intoxication (Group B). The average Ca2i+ level in Group A was higher than the normal value but did not reach a statistical significance (170.8 +/- 9.09 vs 161.6 +/- 30.2, NS). The Ca2i+ level during digitalis toxicity in Group B was significantly higher than that in Group A (201.7 +/- 17.65 vs 170.18 +/- 91.09, P less than 0.01) as well as the normal value (P less than 0.01). With the disappearance of digitalis toxicity the Ca2i+ level was significantly decreased from 201.7 +/- 17.65 to 171.4 +/- 14.08 (P less than 0.001). Following the elimination of digitalis toxicity the increased digoxin concentration also declined. However, the decline of digoxin concentration did not correlate well with the decline of Ca2i+ (r = -0.57, P greater than 0.05). There is a close association between digitalis-induced arrhythmias and the change of Ca2i+ level, compatible with the tentative mechanism of delayed after depolarization (triggered activity). The poor correlation between the Ca2i+ level and digoxin concentration during the process of digitalis toxicity may suggest the presence of factors other than glycosides concentration to cause increased Cai2+ and arrhythmias.

[A correlative study of ECG and coronary arteriogram findings after acute myocardial infarction].

To evaluate the electrocardiographic value in the prediction of reperfusion state of the infarct-related artery (IRA), serial changes in ST segment elevation were assessed in 38 patients with acute myocardial infarction (AMI). ST segment elevation decreased by 35% or more within 8 hours of peak sigma ST in 16 of the 20 patients with subtotal occlusion, but in none of the patients with total occlusion of the IRA (P less than 0.01). Myocardial infarct size estimated by peak serum CK-MB, sigma Q and QRS score was smaller and left ventricular function was better in patients with rapid resolution of ST segment elevation than in those with persistent ST elevation. The study indicates that a fall of ST segment elevation by 35% or more of the peak sigma ST within 8 hours of infarction may be a useful indicator of early reperfusion of the IRA in patients with AMI.

Value of angina pectoris after myocardial infarction in predicting extent of coronary artery disease.

Clinical, hemodynamic, and angiographic data were examined in 53 patients who underwent catheterization within 6 months of documented acute transmural myocardial infarction (MI). The patients were divided into two groups on the basis of presence (23 patients, group I) or absence (30 patients, group II) of angina pectoris 1 month after MI. Group I patients had more severe coronary artery disease and a greater prevalence of multivessel disease than group II patients. Partial preservation of segmental left ventricular wall function in group I was related to the presence of collateral vessels. In patients with single vessel disease, incidence of spontaneous recanalization of the infarct-related artery was more common in group I as compared with those in group II. It is concluded that angina pectoris after MI suggests multivessel disease or infarct-related artery recanalization. Coronary angiography may be advised in these patients in order to select adequate therapeutic interventions and improve prognosis.

Malignant pheochromocytoma: diagnosis and treatment in fifteen cases.

This study reviews the diagnosis and treatment of 15 patients with malignant pheochromocytoma (MP) between 1958 and 1986 in Shanghai Rui-jin Hospital. The main clinical features consisted of sustained elevation of arterial blood pressure, obviously increased catecholamine secretion and a sustained positive phentolamine test. Out of 15 patients only seven survived, two of whom suffered from paraplegia due to metastatic cordal compression. Compared with some earlier results, the prognosis was unsatisfactory. There were several factors which may have been responsible: (1) late diagnosis; (2) incomplete operation, and (3) no regular post-operative assessment of urinary biochemical changes. Because MP is a tumour with a low degree of malignancy, noting the above three factors and using 131I-MIBG to obtain accurate diagnosis and effective treatment enables a better prognosis of this disease.