Prevalence and correlates of physiological valvular regurgitation in healthy subjects.

BACKGROUND: Although echo Doppler machines have consistently advanced within a quarter of a century, age related prevalence of valvular regurgitation detected by currently available echo machines remains uncertain. The aim of this study was to investigate the prevalence and correlates of valvular regurgitation in healthy individuals. METHODS AND RESULTS: A total of 1,333 apparently healthy individuals were enrolled in this study. Echocardiographic examinations were performed using a currently available echo machine. Aortic regurgitation (AR) was detected less frequently (<10%) in younger subjects. Prevalence of aortic regurgitation increased with advancing age and reached 46% in their 9th decade. Mitral regurgitation (MR) was detected in two-thirds of the subjects >30 years old. Tricuspid regurgitation (TR) was frequently (>80%) detected in all age groups. In general, prevalence of valvular regurgitation was higher than those reported previously, except for a relatively lower prevalence of AR in the elderly population. Age was an independent correlate of AR and MR, but not of TR. The presence of AR and MR were independent correlates of TR. CONCLUSIONS: In healthy subjects, AR, MR or TR are commonly detected by using a current echo machine. These "physiological" valvular regurgitations should not be considered as a "pathological" valvular heart disease.

Acute hemodynamic benefits of bi-atrial atrioventricular sequential pacing with the optimal atrioventricular delay.

OBJECTIVES: We evaluate the acute effects on hemodynamics of bi-atrial (BiA) pacing with the optimal atrioventricular (AV) delays, in comparison with high right atrial (HRA) pacing and coronary sinus (CS) pacing. BACKGROUND: Bi-atrial pacing has been suggested as one of the alternative therapy for preventing the recurrence of atrial fibrillation (AF). There are, however, few reports on the hemodynamic effects of BiA pacing, and the results that exist are controversial. METHODS: Twenty patients were paced from HRA, left lateral site of CS, and both sites with the optimal AV delays at 80 and 100 beats/min, in random order. After 5-min pacing, maximal P-wave duration in a 12-lead electrocardiogram, cardiac output (CO), pulmonary capillary wedge pressure (PCWP), and the transmitral flow pattern by transthoracic echocardiography were measured. RESULTS: Compared with HRA and CS pacing, BiA pacing delivered the shortest P-wave duration (HRA: 130 +/- 14 ms, CS: 132 +/- 19 ms, and BiA: 94 +/- 8 ms, respectively, p < 0.001) and the most improvement in CO and PCWP (HRA: 3.63 +/- 0.67 l/min and 9.2 +/- 4.3 mm Hg, CS: 3.71 +/- 0.70 l/min and 8.8 +/- 3.4 mmHg, and BiA: 3.88 +/- 0.63 l/min and 8.0 +/- 3.1 mmHg, respectively, p < 0.01). Bi-atrial pacing also significantly increased the mitral flow time velocity integral and peak A-wave velocity by transthoracic echocardiography, compared with HRA and CS pacing (HRA: 7.6 +/- 1.4 cm and 68.8 +/- 12.2 cm/s, CS: 7.8 +/- 1.4 cm and 70.5 +/- 14.5 cm/s, and BiA: 8.2 +/- 1.2 cm and 76.3 +/- 14.2 cm/s, respectively, p < 0.01). Bi-atrial pacing most significantly decreased the intervals between the atrial pacing spike and the peak of A-wave (HRA: 180 +/- 28 ms, CS: 165 +/- 21 ms, and BiA: 157 +/- 19 ms, respectively, p < 0.01). These improvements in hemodynamics significantly correlated with interatrial conduction delay. CONCLUSIONS: Bi-atrial pacing made the most significant improvements of hemodynamics. These benefits may be due to the improvements in interatrial conduction delay and atrial dyssynchrony.

Incidence and predictors of plaque rupture in the peripheral arteries.

BACKGROUND: Plaque rupture may be present in the peripheral arteries of the patients at high risk for cardiovascular events and is possibly associated with vascular vulnerability. METHODS AND RESULTS: One hundred one iliofemoral arteries from 101 patients undergoing angioplasty were studied. Intravascular ultrasound imaging was performed before intervention. Plaque rupture was defined as presence of a cavity that communicated with the lumen with an overlying residual fibrous cap fragment. Incidence, numbers, and location of the plaque rupture were investigated. Plaque rupture was found in 42 of 101 arteries (42%). Patients with plaque rupture had significantly higher prevalence of acute coronary syndrome than did patients without plaque rupture (42% vs 16%, P=0.01). By multivariable logistic regression analysis, acute coronary syndrome (P=0.004) and male sex (P=0.01) were independent clinical correlates of plaque rupture. During follow-up (median, 14.7 months), the incidence of major adverse cardiac or cerebrovascular events (death, myocardial infarction, and ischemic stroke) was similar between the 2 groups. The incidence of major adverse cardiac or cerebrovascular events plus peripheral vascular events (unplanned vascular intervention and amputation) was significantly higher in patients with plaque rupture than in patients without plaque rupture (46% vs 21%, P=0.008). By multivariable Cox regression analysis, plaque rupture (hazard ratio=2.80, 95% CI: 1.23 to 6.37, P=0.01) and Fontaine stage IV (hazard ratio=3.50, 95% CI: 1.58 to 7.71, P=0.002) were independent predictors of major adverse cardiac or cerebrovascular events plus peripheral vascular events. CONCLUSIONS: Ruptured plaque of the iliofemoral arteries is a common finding. Patients with plaque rupture had a higher prevalence of history of acute coronary syndrome and lower major adverse cardiac or cerebrovascular events plus peripheral vascular event-free survival.

Elevated E/E' predicts prognosis in congestive heart failure patients with preserved systolic function.

BACKGROUND: Although approximately 50% of heart failure patients are reported as heart failure with preserved left ventricular systolic function (HFPSF), echocardiographic prognostic predictors have not been well investigated. Recently, the tissue Doppler-derived index, the ratio of the early transmitral flow velocity and the early mitral annular velocity (E/E'), was reported as useful in predicting prognosis of patients with heart diseases. The purpose of this study was to investigate whether E/E' predicts prognosis in HFPSF. METHODS AND RESULTS: A total of 50 patients with HFPSF (ejection fraction >50%) were consecutively enrolled and studied. Echocardiographic examination was performed on admission and repeated after optimized medical therapy. Cardiac events were defined as death and unplanned hospitalization because of congestive heart failure. Cardiac event-free survival curves from patients with E/E' >15 and E/E' 15 after medical therapy showed significantly lower cardiac event-free survival than patients with E/E' 15 after medical therapy was the only independent predictor of cardiac events (P=0.037, risk ratio=6.1, 95% confidence interval: 1.12-33.3) in patients with HFPSF. CONCLUSIONS: Elevated E/E' after optimized medical therapy may be useful in predicting cardiac events in patients with HFPSF.

Age- and gender-specific changes in the left ventricular relaxation: a Doppler echocardiographic study in healthy individuals.

BACKGROUND: Although left ventricular diastolic function has been shown to deteriorate with advancing age, its gender-specific change is unknown. The aim of this study was to investigate age- and gender-specific changes in tissue Doppler-derived left ventricular diastolic index, E'. METHODS AND RESULTS: A total of 1333 healthy individual without known heart disease or hypertension (mean age, 55 years; range, 10 to 89) were enrolled and studied. Peak early mitral annular velocity (E') and peak late mitral annular velocity (A') were recorded and measured. As an index of the left ventricular relaxation, E' was used. As an index of the left ventricular filling pressure, E/E' was calculated. Although systolic indices poorly correlated with age, diastolic indices correlated well with age. Among those aged 30 to 39 and 40 to 49 years, E' was significantly lower in males than in females. In subjects aged 50 to 59 and 60 to 69 years, E' was similar in both genders. Among those aged 70 to 79 and 80 to 89 years, E' was significantly lower in females than in males. Predictors of the lowest quartile of E' among subjects aged >50 years were age (P<0.0001; chi(2)=66.11; odds ratio, 1.08; 95% CI, 1.058 to 1.097) and female gender (P=0.002; chi(2)=9.23; odds ratio, 1.68; 95% CI, 1.202 to 2.343). CONCLUSIONS: Age-related changes in diastolic indices were gender specific. In the elderly population, diastolic function deteriorated more significantly in the female gender than in the male gender. These results may explain the relatively higher incidence in elderly females among patients with diastolic heart failure and higher cardiovascular mortality in the female gender.

A prospective, multicenter, randomized trial to assess efficacy of pioglitazone on in-stent neointimal suppression in type 2 diabetes: POPPS (Prevention of In-Stent Neointimal Proliferation by Pioglitazone Study).

OBJECTIVES: The aim of this study was to clarify whether pioglitazone suppresses in-stent neointimal proliferation and reduces restenosis and target lesion revascularization (TLR) after percutaneous coronary intervention (PCI). BACKGROUND: Previous single-center studies have demonstrated the anti-restenotic effect of a peroxisome proliferator-activated receptor gamma agonist, pioglitazone, after PCI. METHODS: A total of 97 patients with type 2 diabetes mellitus (T2DM) undergoing PCI (bare-metal stents only) were enrolled. After PCI, patients were randomly assigned to either the pioglitazone group (n = 48) or the control group (n = 49). Angiographical and intravascular ultrasound (IVUS) imaging were performed at baseline and repeated at 6-month follow-up. Primary end points included angiographical restenosis and TLR at 6 months follow-up. Secondary end point was in-stent neointimal volume by IVUS. RESULTS: Baseline glucose level and glycosylated hemoglobin (HbA1c) level were similar between the pioglitazone group and the control group. Angiographical restenosis rate was 17% in the pioglitazone group and 35% in control group (p = 0.06). The TLR was significantly lower in pioglitazone group than in control group (12.5% vs. 29.8%, p = 0.04). By IVUS (n = 56), in-stent neointimal volume at 6 months showed a trend toward smaller in the pioglitazone group than in the control group (48.0 +/- 30.2 mm(3) vs. 62.7 +/- 29.0 mm(3), p = 0.07). Neointimal index (neointimal volume/stent volume x 100) was significantly smaller in the pioglitazone group than in the control group (31.1 +/- 14.3% vs. 40.5 +/- 12.9%, p = 0.01). CONCLUSIONS: Pioglitazone treatment might suppress in-stent neointimal proliferation and reduce incidence of TLR after PCI in patients with T2DM.

Functional mitral regurgitation predicts prognosis independent of left ventricular systolic and diastolic indices in patients with ischemic heart disease.

OBJECTIVE: The purpose of this study was to investigate the prognostic impact of functional mitral regurgitation (FMR) and tissue Doppler-derived index of left ventricular filling pressure, E/E', on long-term clinical outcome in a broad spectrum of ischemic heart disease. BACKGROUND: FMR has been shown to predict prognosis in patients with myocardial infarction. METHODS: A total of 524 patients with ischemic heart disease were enrolled. Patients were categorized according to the presence (n = 58) or absence (n = 466) of severe FMR. RESULTS: Patients with severe FMR were significantly older. By echocardiography, ejection fraction was significantly lower (43.0% +/- 14.6% vs. 56.4% +/- 12.8%, P < .01) and E/E' was significantly higher (21.3 +/- 9.0 vs. 14.6 +/- 6.4, P < .01) in patients with FMR than without FMR. Event-free (death and congestive heart failure) survival was significantly lower in patients with FMR than in those without (log-rank P < .0001). By multivariate logistic regression analysis, E/E' greater than 15 (relative risk [RR] 3.49; 95% confidence interval [CI] 2.08-5.88, P < .0001), ejection fraction less than 50% (RR 3.33; 95% CI 1.96-5.64, P < .0001), and severe FMR (RR 2.34; 95% CI 1.22-2.48, P = .01) were independent echocardiographic predictors of cardiac events. In further analysis of 116 patients matched by a propensity score, severe FMR remained associated with reduced event-free survival (log-rank P = .004). CONCLUSION: FMR is a strong predictor of cardiac events independently of left ventricular systolic and diastolic indices in patients with ischemic heart disease.

The gravitation of the moon plays pivotal roles in the occurrence of the acute myocardial infarction.

Acute myocardial infarction (AMI) is a social burden. However, being able to predict AMI could lead to prevention. A previous study showed only the relation between the lunar phase and the occurrence of AMI, but the period it takes for the moon to orbit around the earth and the period of the lunar phase differ. This study investigated the effect of the gravitation of the moon on AMI. Data was comprised of 1369 consecutive patients with first AMI at 5 hospitals from October, 1984 to December, 1997. The universal gravitation of the moon was calculated and compared to the earth onset time of AMI. Universal gravitation of the moon was derived by G*m/d(2) (G: universal gravitation constant, m: the mass of the moon, d: the distance between the center of the moon and the center of the earth). The relationship between m/d(2) and the cases of AMI was determined. There was an increase in cases, when there is a distance of more than 399864 km from the center of the earth to the center of the moon. The gravitation of more than 399864 km was determined to be weaker gravitation. It is confirmed that the number of AMI patients significantly increases at weaker gravitation periods in this multicenter trial. In conclusion, these results suggest that the gravitation of the moon may have an influence on the occurrence of AMI.

Atherosclerotic plaque with ultrasonic attenuation affects coronary reflow and infarct size in patients with acute coronary syndrome: an intravascular ultrasound study.

BACKGROUND: No reflow following percutaneous coronary intervention (PCI) is a major concern in patients with acute coronary syndrome (ACS) and it may be influenced by the preexisting plaque type. METHODS AND RESULTS: To evaluate the impact of plaque characteristics on coronary reflow following PCI in patients with ACS, a total of 110 patients (89 acute myocardial infarction, 21 unstable angina) were assessed by intravascular ultrasound. Plaque type was categorized as either atherosclerotic plaque without ultrasonic attenuation (group 1) or atherosclerotic plaque with attenuation (group 2). External elastic membrane, plaque plus media, and lumen area were measured. Coronary flow was assessed by Thrombolysis in Myocardial Infarction (TIMI) grade and TIMI frame count. Although the final TIMI frame count was similar between the 2 groups, TIMI frame count immediately after the first balloon inflation was significantly higher in group 2 (p=0.03). Despite the similar final TIMI grade and TIMI frame count, peak creatine kinase level was significantly higher (3,035+/-2,553 vs 1,950+/-1,958 IU/L, p=0.04) and fatal arrhythmia more frequently observed (16.4% vs 2.7%, p=0.04) in group 2 than in group 1. CONCLUSIONS: Atherosclerotic plaque with ultrasonic attenuation may be related to a transient deterioration in coronary flow and as a result larger infarct size and higher incidence of fatal arrhythmia following PCI in patients with ACS. These results may help in selecting lesions suitable for distal protection devices.

Impact of arterial remodelling and plaque rupture on target and non-target lesion revascularisation after stent implantation in patients with acute coronary syndrome: an intravascular ultrasound study.

OBJECTIVES: To investigate the impact of arterial remodelling on long-term clinical outcome after stent implantation in patients with acute coronary syndrome (ACS). METHODS: 134 patients with ACS were enrolled. External elastic membrane (EEM) cross-sectional area (CSA) and lumen CSA were measured. Plaque and media CSA was calculated as EEM minus lumen CSA. Final minimal stent area (MSA) was also measured after stenting. Positive remodelling (PR) was defined as the ratio of the EEM CSA at the target lesion to that at the proximal reference of >1.05, and intermediate or negative remodelling (IR/NR) was defined as that of < or =1.05. RESULTS: Although final MSA was similar, target lesion revascularisation (TLR) rates at 2 years were significantly higher in patients with PR (33.7%) than in those with IR/NR (13.7%; p = 0.01). In addition, non-TLR rates were also significantly higher in patients with PR (42.2%) than in those with IR/NR (23.5%; p = 0.03). Cardiac event-free survival (for events such as death, myocardial infarction, TLR and non-TLR) was significantly lower in patients with PR than in those with IR/NR (log rank, p = 0.001). By multivariate logistic regression analysis, PR (chi2 6.57, OR 2.70; 95% CI, 1.27 to 5.78; p = 0.01) and plaque rupture (chi2 4.17, OR 2.38; 95% CI, 1.04 to 5.45; p = 0.04) were independent predictors of cardiac events. CONCLUSION: In patients with ACS, PR and intravascular ultrasound findings that may correspond with plaque rupture predict cardiac events including both TLR and non-TLR at 2 years.

Impact of statin therapy on systemic inflammation, left ventricular systolic and diastolic function and prognosis in low risk ischemic heart disease patients without history of congestive heart failure.

OBJECTIVES: The aim of this study was to investigate the impact of statin on systemic inflammation, left ventricular systolic and diastolic function and prognosis in low risk ischemic heart disease (IHD) patients. METHODS: A total of 430 consecutive IHD patients without congestive heart failure were enrolled. One hundred and thirty-two patients (31%) were treated with statin (statin group) and 298 patients (69%) were not (no statin group). Echocardiographic indices, high sensitivity CRP, and prognosis were compared. RESULTS: Ejection fraction (EF) was significantly higher in the statin group (p<0.01). The ratio of the early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/E') was significantly lower in the statin group than in the no statin group (p<0.01). Although LDL-cholesterol level did not differ, high sensitivity CRP level was significantly lower in the statin group (0.3+/-0.5 vs. 1.1+/-2.3 mg/dl, p=0.005). Cardiac event-(cardiac death and congestive heart failure)free survival rate was significantly higher in the statin group than in no statin group (Log-rank p<0.0001). By multivariate logistic regression analysis, E/E' > 15 (p=0.002), EF < 50% (p=0.003), lack of statin use (p=0.009), left atrial dimension (p=0.02), use of diuretics (p=0.03) and lack of beta-blockers (p=0.04) were independent predictors of cardiac events. In 248 patients matched by propensity scores, statin remained associated with better event-free survival (Log-rank p=0.006). CONCLUSION: Statin may improve left ventricular function and thus improve the prognosis in low risk patients with IHD.

The relationship between coronary plaque characteristics and small embolic particles during coronary stent implantation.

OBJECTIVES: We investigated the relationship between coronary plaque components and small embolic particles during stenting and examined the influence on the coronary microcirculation. BACKGROUND: In vivo tissue characterization of atherosclerotic plaques was introduced by the Virtual Histology intravascular ultrasound (VH-IVUS) system (Volcano Therapeutics, Inc., Rancho Cordova, California). METHODS: The study consisted of 44 patients who underwent elective coronary stenting. Plaque characteristics were identified with VH-IVUS, and small embolic particles liberated during stenting were detected as high-intensity transient signals (HITS) with a Doppler guidewire. Coronary flow velocity reserve (CFVR) was also measured before and after stenting. RESULTS: Patients were divided into the tertiles according to the HITS counts: the lowest, HITS <5 (n = 16); the middle, 5 to 12 (n = 15); and the highest, >12 (n = 13). Dense calcium and necrotic core area identified with VH-IVUS were significantly larger in the highest tertile (lowest vs. middle vs. highest; dense calcium: 0.2 +/- 0.3 mm2 vs. 0.3 +/- 0.6 mm2 vs. 0.8 +/- 0.7 mm2, p = 0.007; necrotic core: 0.5 +/- 0.4 mm2 vs. 0.9 +/- 0.9 mm2 vs. 1.8 +/- 1.0 mm2, p < 0.001, respectively). Multivariate logistic regression analysis revealed only necrotic core area was an independent predictor of high HITS counts (odds ratio 4.41, p = 0.045). Furthermore, there was a significant negative correlation between the HITS count and CFVR after stenting (r = -0.35, p = 0.017). CONCLUSIONS: The necrotic core component identified with VH-IVUS is related to liberation of small embolic particles during coronary stenting, which results in the poorer recovery of CFVR.

Noninvasive diagnosis of ischemic and nonischemic cardiomyopathy using coronary flow velocity measurements of the left anterior descending coronary artery by transthoracic Doppler echocardiography.

OBJECTIVES: The purpose of this study was to assess the feasibility and usefulness of coronary flow velocity measurements of the left anterior descending coronary artery (LAD) by transthoracic Doppler echocardiography (TTDE) to differentiate ischemic cardiomyopathy (ICM) from non-ICM in patients. BACKGROUND: ICM and non-ICM have similar 2-dimensional echocardiographic features, left ventricular dilatation, and diffuse wall-motion abnormalities. TTDE may be useful to differentiate ICM from non-ICM by detecting significant LAD stenosis based on LAD flow signal analysis. METHODS: TTDE was performed in 52 consecutive patients with left ventricular dilatation and diffuse wall-motion abnormalities of unknown origin. Peak and averaged systolic and diastolic flow velocities of the distal LAD flow could be recorded and measured from 44 patients (85%). Peak and mean diastolic/systolic velocity ratio (DSVR) were calculated. RESULTS: By coronary angiogram, 13 patients were given the diagnosis of ICM and 31 of non-ICM. Left ventricular end-diastolic and end-systolic volumes and ejection fraction were similar between ICM and non-ICM. On the other hand, peak DSVR (1.47 +/- 0.38 vs 2.34 +/- 0.67, P < .0001) and mean DSVR (1.40 +/- 0.42 vs 2.24 +/- 0.61, P < .0001) were significantly lower in patients with ICM than non-ICM. Either peak DSVR less than 1.8 or mean DSVR less than 1.8 had a sensitivity of 77% and a specificity of 77% for detecting the presence of severe LAD stenosis and, therefore, the diagnosis of ICM. CONCLUSION: TTDE is a useful noninvasive method to differentiate ICM from non-ICM.

Utility of right precordial leads at higher intercostal space positions to diagnose Brugada syndrome.

We encountered a patient with Brugada syndrome whose body surface ECG revealed that the specific ST-segment elevation was found only at higher positions of leads V1 and V2, above the third intercostal space. Only these right precordial leads at higher intercostal space positions were useful to identify Brugada syndrome in this case.

Coronary flow reserve correlates left ventricular diastolic dysfunction in patients with dilated cardiomyopathy.

The relationship between altered coronary circulation and left ventricular (LV) function in dilated cardiomyopathy (DCM) remains unclear. We used the Doppler guidewire and transthoracic echo Doppler in 24 DCM patients to investigate the relationship between coronary flow reserve (CFR) and LV systolic/diastolic function, trying to predict diastolic dysfunction and evaluate DCM severity with CFR. CFR correlated better with the deceleration time (DT) of the E-wave and the ratio of E-wave peak value to that of the A-wave (E/A) than with LV ejection fraction (EF). The optimal CFR cutoff value for predicting the restrictive pattern of transmitral flow velocity (DT = 120 msec) was 2.6 (sensitivity 91%, specificity 100%). Dividing patients into two groups around the CFR = 2.6 cutoff, differences in DT and E/A between groups were more prominent than those for EF. CFR correlates better with LV diastolic than systolic function and may be useful for predicting diastolic dysfunction in DCM patients.