Background: Many patients with chordae tendineae rupture (CTR) of the mitral valve have obscure aetiologies. The association between pre-existing hypertension and idiopathic CTR was investigated. Methods: 494 patients with CTR were identified by searching the computer database. For each patient with idiopathic CTR, three matched controls without CTR who were admitted to the same hospital for bone fractures were included. Results: Among the 494 patients with CTR, 351 patients (71%) had idiopathic CTR, and 143 patients (29%) had secondary CTR. The prevalence of pre-existing hypertension was significantly higher in the idiopathic than in the secondary CTR group (50.9% vs 14.6%, p<0.001). The odds ratio was 6.0 (95% CI 3.6 to 10.1). The percentage of patients without adequate blood pressure control was also higher in the idiopathic than in the secondary CTR group (23.1% vs 4.9%, p<0.001). When compared with the fracture group, patients with idiopathic CTR also had a significantly higher prevalence of hypertension (50.9% vs 14.9%, p<0.001), and the odds ratio was 5.9 (95% CI 4.5 to 7.8). After correction for age, the odds ratio of having hypertension was 3.6 (95% CI 2.1 to 6.3) and 6.6 (p<0.001, 95% CI 5.0 to 8.8) when compared with the secondary CTR group and fracture group respectively. Conclusions: There is a strong association between pre-existing hypertension and idiopathic CTR. Whether or not this disease can be prevented by controlling hypertension deserves further investigation.

Background and purpose: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that prevents the fructose‐induced arterial stiffening in male Wistar rats. Our aims were to examine whether AG produced benefits on the left ventricular (LV)‐arterial coupling in fructose‐fed (FF) animals in terms of the ventricular and arterial chamber properties. Experimental approach: Rats given 10% fructose in drinking water (FF) were daily treated with AG (50 mg·kg −1 , i.p.) for 2 weeks and compared with the untreated FF group. In anaesthetised rats, LV pressure and ascending aortic flow signals were recorded to calculate LV end‐systolic elastance ( E es , an indicator of myocardial contractility) and effective arterial volume elastance ( E a ). The optimal afterload ( Q load ) determined by the ratio of E a to E es was used to measure the coupling efficiency between the left ventricle and its vasculature. Key results: There was a significant interaction between fructose and AG in their effects on E a . Fructose loading significantly elevated E a and AG prevented the fructose‐derived deterioration in arterial chamber elastance. Both fructose and AG affected E es and Q load , and there was an interaction between fructose and AG for these two variables. Both E es and Q load exhibited a decline with fructose feeding but showed a significant rise after AG treatment in the FF rats. Conclusions and Implications: AG prevented not only the contractile dysfunction of the heart caused by fructose loading, but also the fructose‐induced deterioration in matching left ventricular function to the arterial system. British Journal of Pharmacology (2007) 151 , 341–346; doi: 10.1038/sj.bjp.0707223

BACKGROUNDThe combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding.METHODSWe randomly assigned 20,078 patients with acute coronary syndromes to receive either fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days (the primary outcome); major bleeding; and their combination. Patients were followed for up to six months.RESULTSThe number of patients with primary-outcome events was similar in the two groups (579 with fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; hazard ratio in the fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the fondaparinux group at 30 days (805 vs. 864, P=0.13) and at the end of the study (1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent]; hazard ratio, 0.52; P<0.001). The composite of the primary outcome and major bleeding at nine days favored fondaparinux (737 events [7.3 percent] vs. 905 events [9.0 percent]; hazard ratio, 0.81; P<0.001). Fondaparinux was associated with a significantly reduced number of deaths at 30 days (295 vs. 352, P=0.02) and at 180 days (574 vs. 638, P=0.05).CONCLUSIONSFondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity. (ClinicalTrials.gov number, NCT00139815.).

BACKGROUND:We determined the effects of NIDDM on haemodynamic parameters describing arterial wall elasticity and cardiac hypertrophy in rats administered streptozotocin (STZ) and nicotinamide (NA), using the aortic impedance analysis.METHODS:Male Wistar rats at 2 months were administered intraperitoneally 180 mg kg(-1) of NA, 30 min before an intravenous injection of 50 mg kg(-1) STZ, to induce type 2 diabetes. The STZ-NA rats were divided into two groups, 4 weeks and 8 weeks after induction of diabetes, and compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured by a high-fidelity pressure sensor and electromagnetic flow probe, respectively, and were then subjected to Fourier transformation for the analysis of aortic input impedance.RESULTS:In each diabetic group, the experimental syndrome was characterized by a moderate and stable hyperglycaemia and a relative deficiency of insulin secretion. However, the 8-week but not the 4-week STZ-NA diabetic rats showed a decrease in cardiac output in the absence of any significant changes in mean aortic pressure, having increased total peripheral resistance. The diabetic syndrome at 8 weeks also contributed to an increase in aortic characteristic impedance, from 1.49 +/- 0.33 (mean +/- SD) to 1.95 +/- 0.28 mmHg s mL(-1) (P < 0.05), suggesting a detriment to the aortic distensibility in NIDDM. Meanwhile, the STZ-NA diabetic animals after 8 weeks had an increased wave reflection factor (0.46 +/- 0.09 vs. 0.61 +/- 0.13, P < 0.05) and decreased wave transit time (25.8 +/- 3.8 vs. 20.6 +/- 2.8 ms, P < 0.05). Ratio of the left ventricular weight to body weight was also enhanced in the 8-week STZ-NA diabetic rats.CONCLUSION:The heavy intensity with early return of the pulse wave reflection may augment systolic load of the left ventricle coupled to the arterial system, leading to cardiac hypertrophy in the rats at 8 weeks after following STZ and NA administration.

BACKGROUND:Formation of advanced glycation end-products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in rats.MATERIALS AND METHODS:The NIDDM was induced in male Wistar rats, which were administered intraperitoneally with 180 mg kg(-1) nicotinamide (NA) 30 min before an intravenous injection of 50 mg kg(-1) streptozotocin (STZ). After induction of diabetes mellitus type 2, animals receiving daily peritoneal injections with 50 mg kg(-1) AG for 8 weeks were compared with the age-matched, untreated, diabetic controls.RESULTS:After exposure to AG, the STZ-NA diabetic rats had improved aortic distensibility, as evidenced by 18.8% reduction of aortic characteristic impedance (P < 0.05). Treatment of the experimental syndrome with AG also resulted in a significant increase in wave transit time (+23.7%, P < 0.05) and a decrease in wave reflection factor (-26.6%, P < 0.05), suggesting that AG may prevent the NIDDM-induced augmentation in systolic load of the left ventricle. Also, the glycation-derived modification on aortic collagen was found to be retarded by AG. The diminished ratio of left ventricular weight to body weight suggested that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening.CONCLUSIONS:Long-term administration of AG to the STZ-NA diabetic rats imparts significant protection against the NIDDM-derived impairment in vascular dynamics, at least partly through inhibition of the AGE accumulation on collagen in the arterial wall.

The formation of advanced glycation endproducts (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study was to examine the role of aminoguanidine (AG), an inhibitor of AGEs formation, in the prevention of arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) induced diabetes in rats. Diabetes was induced in animals by a single tail vein injection with 65 mg kg−1 STZ. After confirmation of the development of hyperglycemia (2 days later), rats were treated for 8 weeks with AG (daily peritoneal injections of 50 mg kg−1) and compared with the age‐matched untreated diabetic controls. After exposure to AG, the STZ‐diabetic rats showed no alterations in cardiac output, aortic pressure profiles, total peripheral resistance, and aortic characteristic impedance. By contrast, treatment of this experimental diabetes with AG resulted in a significant increase in wave transit time (τ), from 20.4±0.6 to 24.7±0.5 ms (P<0.05) and a decrease in wave reflection factor (Rf), from 0.78±0.04 to 0.53±0.02 (P<0.05). The decreased Rf associated with the increased τ suggest that AG may retard the diabetes‐induced augmentation in systolic load of the left ventricle coupled to its arterial system. Meanwhile, the diminished ratio of left ventricular weight to body weight suggests that prevention of the diabetes‐related cardiac hypertrophy by AG may correspond to the drug‐induced decline in aortic stiffening. Glycation‐derived modification on aortic collagen was also found to be enhanced in rats with diabetes (+65.3%, P<0.05) and the advanced glycation process was retarded by AG treatment. We conclude that long‐term administration of AG to the STZ‐treated rats imparts significant protection against the diabetes‐derived deterioration in vascular dynamics, at least partly through inhibition of the AGEs accumulation on collagen in the arterial wall. British Journal of Pharmacology (2006) 147, 944–950. doi:10.1038/sj.bjp.0706684

Background Human minK protein is the β-subunit of IKs potassium channel and plays an important role in cardiac cellular electrophysiology. We investigated the association between human atrial fibrillation and the polymorphism of minK gene (38G or 38S) with a case-control study. Methods We included 108 patients with atrial fibrillation and 108 control subjects. The case patients and control subjects were matched regarding age, sex, presence of valvular heart disease, and presence of left ventricular dysfunction. The genotype of minK was determined with polymerase chain reaction and restriction fragment analysis. Results The results showed an association between the minK 38G allele and atrial fibrillation. The odds ratios for atrial fibrillation in patients with 1 and 2 minK 38G alleles were 2.16 (95% CI 0.81-5.74) and 3.58 (95% CI 1.38-9.27), respectively, when compared with patients without minK 38G allele. In a logistic regression model, the odds ratio for atrial fibrillation was 1.80 (95% CI 1.20-2.71, P <.0046) for patients with 1 more minK 38G allele. Conclusion We report the association between the minK 38G allele and clinical atrial fibrillation. Our findings suggest possible genetic control on the pathogenesis of atrial fibrillation. (Am Heart J 2002;144:485-90.)

Ticlopidine is a powerful antiplatelet activator that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. Its most common side-effects are skin rashes, diarrhea and neutropenia. Aplastic anemia is rare. This paper reports a patient with severe aplastic anemia that developed after the use of ticlopidine. The 85-year-old woman developed fever, chills and chest pain 5 weeks after starting ticlopidine 250 mg twice daily. Severe aplastic anemia was proved by blood examination, bone marrow aspiration and biopsy. In spite of the recovery of absolute neutrophil count to more than 1,000/mm3, 16 days after ticlopidine was stopped and administration of strong antibiotics, the patient died from candidal sepsis.

The ability of electrocardiograms (ECG), vectorcardiograms (VCG) and body surface potential maps (BSPM) to predict left ventricular asynergy was evaluated in 100 consecutive patients with coronary artery disease, 51 patients (51%) of whom with and 49 (49%) without ventricular asynergy. With regard to the diagnosis of ventricular asynergy, the electrocardiographic sign of pathologic Q waves had a sensitivity of 58.8%, a specificity of 44.9%, a positive predictive value of 52.6%, and a negative predictive value of 51.2%. The vectorcardiographic pattern of myocardial infarction gave the corresponding predictive value of 66.7, 46.9, 56.7 and 57.5%, respectively. Finally, the so-called abnormal 'early reversal' BSPM - the abnormal BSPM pattern with absolute value of potential minimum over potential maximum in the early ventricular depolarization - achieved the corresponding predictive value of 84.3, 71.4, 75.4 and 81.4% respectively. Our data suggest that: (1) BSPM is useful in the detection of left ventricular asynergy, and (2) BSPM is superior to ECG and VCG in the diagnosis of left ventricular asynergy.