Sex difference in pulmonary hypertension in the evaluation by exercise echocardiography.

Male patients with pulmonary hypertension have poor survival than their female counterparts. Poor right ventricular function in men may be one of the major determinants of poor prognosis. This study aimed to investigate the difference in hemodynamics during exercise between men and women by exercise echocardiography. Consecutive patients with pulmonary hypertension who underwent right heart catheterization were enrolled, and survival was analyzed. In patients who underwent exercise echocardiography, the change in tricuspid regurgitation pressure gradient during exercise was calculated at multiple stages (low-, moderate-, and high-load exercise), and the mortality was also recorded. In a total of 93 patients, although there were no differences in pulmonary artery pressure and vascular resistance between sexes, male patients showed poor survival. In patients with exercise echocardiography, change in tricuspid regurgitation pressure gradient at low-load (25 W) exercise was significantly lower in men, although that at maximum-load exercise was not different between men and women. In the Kaplan-Meier analysis, in a median follow-up duration of 1760 days, male patients and those with lower change in tricuspid regurgitation pressure gradient at low-load exercise showed poorer survival (P = 0.002 and 0.026, respectively). In the Cox proportional hazards analysis, the change in tricuspid regurgitation pressure gradient at low-load exercise was independently associated with poor survival after adjustment for age and sex. In conclusion, a lower change in tricuspid regurgitation pressure gradient at low-load exercise was observed in male patients and was a prognostic marker, which may be associated, at least in part, with poorer prognosis in male patients with pulmonary hypertension.

Efficacy and Safety of an Orally Administered Selective Prostacyclin Receptor Agonist, Selexipag, in Japanese Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Selexipag is an orally available prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. In this open-label Phase II trial, the efficacy and safety of selexipag in Japanese patients with pulmonary arterial hypertension (PAH) is examined.Methods and Results:Selexipag was administered at 200 µg twice daily and titrated up to 1,600 µg by increments of 200 µg in 37 subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33 patients comprising the per-protocol set, the pulmonary vascular resistance (PVR; primary endpoint) decreased from 683.2±237.3 to 560.3±238.7 dyn·s/cm5(P<0.0001). For the secondary endpoint, the 6-min walk distance (6MWD) increased from 445.0±102.2 to 459.1±112.8 m (P=0.0324); World Health Organization functional class improved in 4 patients (12.1%), and was maintained in 29 patients (87.9%). A decrease in PVR was also shown in patients treated with selexipag, on top of a phosphodiesterase inhibitor and endothelin receptor antagonist. Most of the commonly reported adverse events were consistent with those reported for other PGI2formulations. Thirty-four patients attained the individual maximum tolerated dose (maintenance dose). CONCLUSIONS: The efficacy and tolerability of selexipag in Japanese PAH patients was confirmed by improvement in pulmonary hemodynamics, exercise capacity, symptoms. Selexipag is an efficacious treatment option for Japanese PAH patients. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111532].).

Effects of the endothelin receptor antagonist bosentan on hemodynamics and exercise capacity in Japanese patients with mildly symptomatic pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) trial has mostly enrolled patients with World Health Organization functional class (WHO FC) III or IV. However, PAH is rapidly progressive in nature even in patients with less severe forms at diagnosis. Following the recent studies in Western population, here we assessed the efficacy of bosentan in Japanese patients with WHO FCII PAH. In this open-label trial, bosentan 125 mg twice daily was administered for 12 weeks in 16 patients, and a hemodynamic evaluation was performed. Treatment was continued for a further 12 weeks, where the effect on exercise capacity was assessed in 13 patients. In 16 patients, mean pulmonary arterial pressure decreased from 40.4 ± 10.4 to 35.6 ± 12.6 mmHg (p = 0.018) and cardiac index increased from 2.54 ± 0.73 to 2.96 ± 0.82 L/min/m(2) (p = 0.023). Thus, pulmonary vascular resistance decreased from 792 ± 565 to 598 ± 558 dyn·sec/cm(5) (p = 0.006). In 13 patients followed up for 24 weeks, 6-min walking distance increased from baseline at Week 12 (p = 0.003) and Week 24 (p = 0.011). All patients were mildly symptomatic at baseline with dyspnea index (Borg scale) of 2.50 ± 1.58 and the specific activity scale (SAS) of 5.0 ± 1.4 METs. These values remained unchanged throughout the study. These results suggest that bosentan treatment was beneficial for Japanese patients with WHO FC II PAH and treatment should be started in the early stage of the disease.

[Pulmonary septic embolism with right side infectious endocarditis and ventricular septal defect: a case report].

An 18-year-old man was diagnosed with ventricular septal defect after birth. He was asymptomatic until February 2006. He came to our hospital with remittent fever persisting for 2 months. Chest computed tomography showed multiple infiltrative shadows and alpha-streptococcus was detected on blood cultures. Transesophageal echocardiography detected vegetation (1.3 cm) on the right ventricle wall at the point of impact of the shunted bloodstream. We diagnosed pulmonary septic embolism and began to administer penicillin G and gentamicin. Sixteen days later, a new pulmonary septic embolism appeared, so antibiotic treatment was continued at a higher dose. Two weeks later, the vegetation and infiltrative shadow disappeared. Echocardiography showed the ratio of pulmonary to systemic blood flow was 1.2. These findings indicate that patch closure of ventricular septal defect may be necessary for prevention of recurrence of right side infectious endocarditis.

Calcium antagonists for secondary prevention of myocardial infarction: is there a need to shift from short-acting to long-acting types?

BACKGROUND: Although short-acting nifedipine does not prevent myocardial infarction (MI), calcium antagonists with a long half-life may be effective. METHODS AND RESULTS: The present study was a retrospective analysis of the incidences of cardiac events among patients with a healed MI treated with 3 times-a-day type nifedipine (half-life 1.8 h; n=617), twice-a-day type nifedipine (half-life 4.0 h; n=527) and those not taking calcium antagonists (n=1,593) from 1986 to 1993, and the incidences of those on once-a-day type calcium antagonists (half-life 11.0 h; n=903) and those not taking calcium antagonists (n=2,788) from 1994 to 2001. Cardiac events included cardiac death and nonfatal recurrent MI. Single and multivariate analyses using the Cox-Hazard model were performed. From 1986 to 1993 cardiac events occurred in 38 patients with 3-times-a-day nifedipine (6.2%, hazard ratio and 95% confidence interval: 1.45 and 0.93-2.27), in 18 patients with twice-a-day nifedipine (3.4%: 0.68 and 0.39-1.20), 57 patients without calcium antagonists (3.6%). Cardiac events also occurred in 11 patients with once-a-day type nifedipine (1.2%: 0.72 and 0.37-1.42) and 48 patients without calcium antagonists (1.7%). Of the once-a-day type calcium antagonists, cardiac events were the lowest (2 patients, 0.6%: 0.32 and 0.08-1.31) in patients with amlodipine (half-life 39.0 h; n=334), which has the longest half-life. None of these drugs were a significant factor in the increase or decrease in the incidence of cardiac events. However, there was a good correlation between the half-life of the calcium antagonist and the hazard ratio for reducing cardiac events. CONCLUSION: Although there was a tendency toward a reduction in cardiac events using calcium antagonists with long half-life, none of these drugs could significantly reduce the incidence of cardiac events in patients with a healed MI.

Usefulness of ST-segment elevation in the inferior leads in predicting ventricular septal rupture in patients with anterior wall acute myocardial infarction.

The ventricular septum receives its blood supply from the septal perforators of the left anterior descending (LAD) coronary artery and the right coronary artery. However, when the LAD artery extends to the inferior wall, beyond the apex (so-called wrapped LAD), the ventricular septum near the apex receives blood supply only from the LAD artery. As a consequence, ventricular septal rupture (VSR) would seem more likely in myocardial infarction with occlusion of this type of LAD artery. To test this hypothesis, we compared electrocardiographic findings in 21 patients who had anterior acute myocardial infarction that was complicated by VSR with those in 275 patients who had acute myocardial infarction that was not complicated by VSR. We observed ST-segment elevation in all inferior leads (II, III, and aVF) in addition to anterior leads in 42.9% of patients (9 of 21) who had VSR but in only 3.6% of those (10 of 275) who did not have VSR. Abnormal Q waves appeared in all 3 inferior leads in 44.4% of patients (8 of 18) who had VSR but in only 4.0% of those (10 of 250) who did not have VSR. Thus, the incidence of ST-segment elevation and abnormal Q waves in the inferior leads was significantly (p <0.001) greater in the VSR group. In addition, multivariate analysis of patient characteristics, including advanced age, female gender, and coronary morphology, showed VSR to be significantly correlated with ST-segment elevation (odds ratio 16.93, 95% confidence interval 4.13 to 69.30) and abnormal Q waves (odds ratio 13.64, 95% confidence interval 3.16 to 58.79) in the 3 inferior leads. In conclusion, these electrocardiographic findings can be useful predictors of complication by VSR.

Plaque erosion in the culprit lesion is prone to develop a smaller myocardial infarction size compared with plaque rupture.

BACKGROUND: Acute myocardial infarction (MI) stems from a disruption of the plaque in the coronary artery. Based on postmortem examinations, such plaque disruption has been classified as either a rupture or an erosion. Unfortunately, it has been difficult to clinically identify plaque ruptures and plaque erosions during the development of acute MI. To elucidate the relationships between clinical features and the morphological characteristics of the infarct-related lesions, we observed the culprit lesions in patients with acute MI by coronary angioscopy and intravascular ultrasound. METHODS: We examined culprit lesions in 107 patients with acute MI using coronary angioscopy and intravascular ultrasound immediately before performing percutaneous coronary intervention. The lesions were then classified as plaque ruptures or nonruptured erosions, and their clinical features were compared. RESULTS: Among the lesions studied, 44 were classified as plaque ruptures, 28 were classified as plaque erosions, and 35 were unclassified. Patients with nonruptured eroded plaques had more preinfarction angina before the onset of MI than those with ruptured plaques (53.6% vs 22.7%, P = .0074). They also had less ST-segment elevation MI (71.4% vs 93.2%, P = .0185), lower peak creatine kinase levels (2029 +/- 1517 vs 4033 +/- 2699 IU/L, P = .0009), less distal embolization after percutaneous coronary intervention (3.6% vs 36.4%, P = .0014), and less Q-wave MI 1 month after onset (40.7% vs 88.4%, P < .0001). CONCLUSION: Patients with eroded plaque lesions have smaller infarctions than those with ruptured plaque lesions, suggesting that an eroded plaque is less potently thrombogenic than a ruptured plaque.

Recent decline in hospital mortality among patients with acute myocardial infarction.

BACKGROUND: Many patients with acute myocardial infarction will still die after admission. Recent trends in hospital mortality were analyzed to identify aspects that need improvement. METHODS AND RESULTS: A total of 1,247 patients admitted to Kinki University School of Medicine within 24 h of the onset of infarction were analyzed between 1975 and 2001. The percentage of patients discharged with 100% occlusion decreased gradually from 31.3% during 1975-1982 to 2.1% during 1998-2001, while those with 50% stenosis or less gradually increased from 12.5% to 82.5% during the same period (trends: p < 0.01). The cardiac death rate was 17.1% in 1975-1982, and 7.7% in 1998-2001, showing a significant decrease with time (p < 0.01). This decrease was particularly marked among those admitted within 6 h of the onset of infarction. Death due to cardiac rupture decreased significantly with time (p < 0.001). In contrast, the non-cardiac death rate, amounting to 2.2% on average, did not decline. CONCLUSIONS: Cardiac deaths due to acute myocardial infarction have decreased markedly of late. However, patients must be admitted within 6 h of the onset of infarction to benefit from this improvement. More effort should be made to improve the general care of patients in order to reduce the incidence of non-cardiac death.

Efficacy of coronary angioplasty following conventional coronary thrombolysis in patients with acute myocardial infarction.

The efficacy of combined thrombolysis and angioplasty for the purpose of coronary reperfusion after acute myocardial infarction has been controversial. The present study was conducted, therefore, to evaluate the effects of angioplasty following administration of conventional thrombolytic agents on the long-term prognosis of acute myocardial infarction patients. A total of 409 patients admitted to the hospital within 12 hours of the onset of infarction between January 1990 and May 2001 were studied retrospectively. These included 151 patients treated with thrombolysis alone (group T), 73 patients treated with angioplasty alone (group A), and 35 patients treated with angioplasty after thrombolysis (group T&A). Group T&A had shorter intervals from onset to initial treatment than group A (3.0 hours vs 6.3 hours, p < 0.01), a higher reperfusion success rate than group T (91.4% vs 74.8%, p < 0.01), and more improved left ventricular wall motion than group A. One-year cardiac mortality rates tended to be higher in group T, which had a higher rate of unsuccessful reperfusion than groups T&A or A (8.1% vs 3.4% vs 3.5%). The frequencies of hemorrhagic complications were similar among the 3 groups. From these findings, we conclude that thrombolytic therapy with subsequent angioplasty is an effective strategy for achieving cardiac reperfusion following acute myocardial infarction.

[Diagnosis of vascular complications at the puncture site after cardiac catheterization].

OBJECTIVES: Cardiac catheterization is increasingly used for the diagnosis or treatment of coronary artery disease. Previous studies that revealed the incidence of complications such as arteriovenous fistula and pseudoaneurysm were based on retrospective analysis of cohorts referred to vascular surgery. This study was designed to determine the incidence of arteriovenous fistula and pseudoaneurysm after percutaneous transluminal angiography. METHODS: All 557 consecutive patients undergoing cardiac catheterization were examined by ultrasonography from March 1, 2001 to April 1, 2002, to investigate the occurrence of arteriovenous fistula and pseudoaneurysm at the puncture site. RESULTS: Pseudoaneurysm was found in 16 patients (2.9%), and arteriovenous fistula in 12 patients (2.2%). Pseudoaneurysm in 7 patients (43.8%) and arteriovenous fistula in 6 patients (50.0%) were diagnosed only by ultrasonic examination. There were more female patients (9 patients, 56.3%) than male with pseudoaneurysm (p < 0.01). The puncture site was located after the division of the deep femoral artery and superficial femoral artery in all patients with complications. CONCLUSIONS: Ultrasonic examination was useful for diagnosis of complications such as arteriovenous fistula and pseudoaneurysm after cardiac catheterization.

Pravastatin reduces the incidence of cardiac events among patients with myocardial infarction.

We retrospectively compared the incidence of cardiac events in myocardial infarction (MI) patients treated in our departments between 1990 and 1999 with pravastatin or without cholesterol-lowering agents. Our aim was to evaluate the efficacy of pravastatin in the secondary prevention of MI. Cardiac events--defined as fatal or nonfatal recurrent MI, sudden cardiac death, and death from congestive heart failure--occurred in 8 (2.2%) of 356 MI patients treated with pravastatin (17.1 cases/1.000 person x year) and in 39 (5.6%) of 700 MI patients not treated with cholesterol-lowering agents (54.3 cases/1000 person x year), which represented a significant decline among those taking pravastatin (P < 0.05, odds ratio: 0.39, 95% (CI: 0.18-0.84). Likewise, total mortality was significantly lower among patients treated with pravastatin (18 cases, 5.1%; 38.4 cases/1,000 person x year vs 77 cases, 11.0%; 107.2 cases/1,000 person x year, P < 0.01, odds ratio: 0.43, 95% CI: 0.25-0.73). Subgroup analysis revealed a significantly lower incidence or cardiac events in the pravastatin group for 6 of the items among 53 patient characteristics, and was lower but not significant for 45 items and was greater but not significant only for 2 items. Furthermore, multivariate analysis confirmed pravastatin to be a useful factor for preventing the occurrence of cardiac events in MI patients (P < 0.05, odds ratio: (0.44, 95% CI: 0.20-0.95), and Kaplan-Meier curves also showed pravastatin to significantly reduce the incidence of both cardiac events and total mortality. These findings are consistent with those previously reported by several large-scale clinical trials carried out in Western countries, and demonstrate that pravastatin is useful for secondary prevention of MI in Japanese patients.