Beom-June Kwon

Prognosis of heart failure patients with reduced and preserved ejection fraction and coexistent chronic obstructive pulmonary disease

The long‐term prognosis of patients with heart failure with preserved left ventricular ejection fraction (HFPEF) and coexistent chronic obstructive pulmonary disease (COPD) has not been previously investigated. The primary aim of this study was to determine whether the long‐term prognosis of HFPEF patients with COPD differs from that of heart failure patients with reduced left ventricular ejection fraction (HFREF) and COPD. The secondary aim was to identify independent predictors of event‐free survival in patients with HF and COPD.

Metabolically obese status with normal weight is associated with both the prevalence and severity of angiographic coronary artery disease

OBJECTIVE We evaluated prevalence and severity of angiographic coronary artery disease (CAD) according to groups by metabolically obese (MO) and/or weight status. MATERIAL/METHODS Normal weight was defined as body mass index (BMI, kg/m²)<25 and obesity was defined as BMI≥25. The MO was determined using the National Cholesterol Education Program-Adult Treatment Panel III classification with Korean-specific cutoffs for abdominal obesity. Therefore, a total of 856 subjects were categorized as follows: (1) metabolically healthy and normal weight (MHNW); (2) metabolically obese but normal weight (MONW); (3) metabolically healthy but obese (MHO); and (4) metabolically abnormally obese (MAO). The presence of obstructive lesion≥50% of coronary artery was considered as an angiographic CAD and the Gensini scoring system was used for the severity. RESULTS MONW or MO showed a higher prevalence of CAD than MHNW or non-MO after adjustment for age and sex, respectively (MONW, odds ratio [OR]=1.69, 95% confidence interval [CI]: 1.13-2.51 and MO, OR=1.44, 95% CI: 1.09-1.91). In subjects without diabetes mellitus (DM), MONW or MO showed a marginally higher prevalence of CAD (MONW, OR=1.58, 95% CI: 0.96-2.61 and MO, OR=1.41, 95% CI: 0.96-2.08). MONW was independently associated with a higher severity of angiographic CAD than MHNW after age, sex, glomerular filtration rate, smoking status, high sensitive C-reactive protein, and use of anti-platelet and anti-angina drugs (β=0.118, P=0.005). And MO was associated with a higher severity of angiographic CAD than non-MO after adjustment for age and sex (β=0.077, P=0.024). The above associations were also consistent in subjects without DM (MONW, β=0.147, P=0.003 and MO, β=0.129, P=0.005). CONCLUSIONS MONW or MO is associated with both the prevalence and severity of angiographic CAD after adjustment for age and sex and MONW is independently associated with the severity of angiographic CAD irrespective of DM. Therefore, subjects with MO but normal weight (MONW) should be carefully examined for angiographic CAD.

Comparison of the efficacy between hydrochlorothiazide and chlorthalidone on central aortic pressure when added on to candesartan in treatment-naïve patients of hypertension.

Thiazide-type diuretics are the most commonly used blood pressure (BP)-lowering drug for patients with uncomplicated hypertension. However, it has remained unclear whether hydrochlorothiazide (HCTZ) or chlorthalidone (CTD) shows better improvement in central aortic pressure. We conducted an open-label, randomized, prospective cross-over study with an 8-week active treatment (HCTZ of 25 mg with candesartan of 8 mg or CTD of 12.5 mg with candesartan of 8 mg) with a 4-week washout period (only candesartan during this period). Twenty-eight treatment-naïve patients of hypertension were enrolled (mean age: 50±9 years, male: 44.4%). Central aortic pressure, pulse wave velocity (PWV), augmentation index (AIx) and other BP-derived parameters were measured. After 8 weeks of active treatment, there was no significant difference in changes of central aortic pressure between HCTZ and CTD treatments (Δ=−14±8 vs. −16±7 mm Hg, P=0.645). However, CTD treatment showed a significant reduction in PWV compared with baseline (1321±194 vs. 1439±190 cm s−1, P=0.007) and HCTZ treatment (Δ=−118±82 vs. Δ=5±72 cm s−1, P=0.033), whereas HCTZ treatment showed a marginal, but not a significant reduction in AIx compared with baseline. In conclusion, CTD of 12.5 mg is as potent as HCTZ of 25 mg, when combined with candesartan of 8 mg, in lowering central aortic pressure. In addition, CTD treatment resulted in a significant reduction of PWV.

Systolic synchrony is impaired in nonleft ventricular hypertrophy of never-treated hypertensive patients.

Objective The objective of the current study was to confirm the degrees of dyssynchrony in patients with nonleft ventricular hypertrophy (LVH) and never-treated hypertension compared with normal controls or patients with LVH and never-treated hypertension. Methods and results We enrolled 200 consecutive never-treated hypertensive patients and 104 age-matched and sex-matched normal controls. The following parameters were evaluated by echocardiography comprising conventional Doppler, tissue Doppler imaging, and strain imaging: global dyssynchrony; systolic dyssynchrony (longitudinal); diastolic dyssynchrony; and contractile diastolic dyssynchrony. Systolic dyssynchrony in the LVH group with hypertension was more aggravated than in normal controls (P < 0.001). In addition, global, diastolic, and contractile diastolic dyssynchrony in the LVH group with hypertension were more aggravated than in the non-LVH group with hypertension (all P < 0.001), but systolic dyssynchrony was not different between the two groups. All of the above associations remained significant after adjustment for confounding factors. Conclusion Systolic synchrony was impaired in patients with non-LVH and never-treated hypertension to a similar degree in the LVH group with never-treated hypertension.

Optimal antithrombotic strategy in patients with atrial fibrillation after coronary stent implantation.

Background and Objectives Little evidence is available on the optimal antithrombotic therapy following percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). We investigated the outcomes of antithrombotic treatment strategies in AF patients who underwent PCI. Subjects and Methods Three hundred sixty-two patients (68.0% men, mean age: 68.3±7.8 years) with AF and who had undergone PCI with stent implantation between 2005 and 2007 were enrolled. The clinical, demographic and procedural characteristics were reviewed and the stroke risk factors as well as antithrombotic regimens were analyzed. Results The accompanying comorbidities were as follows: hypertension (59.4%), diabetes (37.3%) and congestive heart failure (16.6%). The average number of stroke risk factors was 1.6. At the time of discharge after PCI, warfarin was prescribed for 84 patients (23.2%). Cilostazol was used in addition to dual antiplatelet therapy in 35% of the patients who did not receive warfarin. The mean follow-up period was 615±385 days. The incidences of major adverse cardiac events (MACE), stroke and major bleeding were 11.3%, 3.6% and 4.1%, respectively. By Kaplan-Meier survival analysis, warfarin treatment was not associated with a lower risk of MACE (p=0.886), but it was associated with an increased risk of major bleeding (p=0.002). Conclusion Oral anticoagulation therapy after PCI may increase hemorrhagic events in Korean AF patients.

Left ventricular diastolic dyssynchrony in patients with treatment-naive hypertension and the effects of antihypertensive therapy.

Aims: The presence of left ventricular diastolic dyssynchrony is well known to be a frequent and important manifestation in heart failure. We investigated diastolic dyssynchrony in patients with treatment-naive hypertension, compared with normal controls; the determinants of the presence of diastolic dyssynchrony by performing comprehensive studies including laboratory, arterial stiffness, central blood pressure (BP), ambulatory BP monitoring (ABPM), and transthoracic echocardiography (TTE) evaluations; the effects of 6-month antihypertensive therapy on diastolic dyssynchrony; and the predictors associated with the change of diastolic dyssynchrony after medical therapy. Methods: A total of 325 treatment-naive hypertensive patients and 172 normal controls were prospectively enrolled. Hypertensive patients were followed up at 6 months after medical therapy, and were assessed by serial TTE (at baseline and 6-month follow-up visit) and clinical evaluations. The time-to-peak myocardial early diastolic velocity (Te) of the 12 left ventricular segments was measured with reference to the QRS complex. The standard deviation (SD) of Te of all 12 left ventricular segments (Te-SD12) and the maximal difference in Te between any two of the 12 left ventricular segments (Te-Max) were calculated. A Te-SD12 at least 34 or Te-Max at least 113 ms was regarded as indicating the presence of diastolic dyssynchrony. Results: Diastolic dyssynchrony was more prevalent in treatment-naive hypertensive patients, compared with normal controls (15.4 versus 7.0%, P = 0.007). Male sex [odds ratio (OR), 9.36 (1.93–45.41)], magnesium [OR per 1 SD, 2.54 (1.32–4.90)], night-time heart rate [HR; OR per 1 SD, 2.44 (1.18–5.05)], and mitral E/A [OR per 1 SD, 0.13 (0.04–0.45)] were independent determinants for the diastolic dyssynchrony in hypertensive patients. A 6-month follow-up, echocardiography was performed in 74 of 275 patients without diastolic dyssynchrony (group 1) and 26 of 50 patients with diastolic dyssynchrony (group 2). Diastolic dyssynchrony (Te-SD12, &Dgr; = −8.3 ms; Te-Max, &Dgr; = −27.6 ms; prevalence, &Dgr; = −42.3%; all P < 0.05) improved in group 2, whereas it did not in group 1. Baseline daytime HR (P = 0.008) and magnesium levels (P = 0.029) and changes of the midwall fractional shortening (P = 0.026), mitral E/A (P = 0.003), mean annulus Ea (P = 0.003), mean annulus Ea/Aa (P = 0.020), and mitral peak E (P = 0.042) were independent predictors for changes of Te-SD12. Conclusion: Diastolic dyssynchrony is not rare in treatment-naive hypertensive patients. Male sex, magnesium levels, night-time HR, and mitral E/A are independent determinants for the impaired diastolic dyssynchrony. Antihypertensive therapy reduces both the severity and prevalence of diastolic dyssynchrony in patients with impaired diastolic dyssynchrony. Daytime HR, magnesium levels, and indications of systolic or diastolic dysfunction are independent predictors for improvements in diastolic dyssynchrony. Thus, magnesium levels, HR, and diastolic dysfunction seem to have important implications for diastolic dyssynchrony in hypertensive patients, whereas left ventricular hypertrophy, office BPs, arterial stiffness, central BPs, and ABPM parameters do not.

Independent determinants for presence and degree of left ventricular systolic dyssynchrony in treatment-naive patients with hypertension.

Objective: Prevalence of left ventricular systolic dyssynchrony (LVSD) is over 40% in treatment-naive patients with hypertension and it improves after chronic antihypertensive treatment. These findings might support the hypothesis that blood pressure (BP), BP-derived parameters, central BP, or arterial stiffness would contribute to LVSD. Therefore, we aimed to investigate possible factors associated with LVSD in treatment-naive patients with hypertension. Methods: The study groups consisted of 266 treatment-naive hypertensive patients who underwent anthropometric, clinical, laboratory, echocardiographic, arterial stiffness, central blood pressure, and 24-h ambulatory blood pressure monitoring evaluations. Echocardiographic measurement was recorded as follows: peak systolic velocity (Sa, subclinical left ventricular systolic function), peak early diastolic and late diastolic velocity at the mitral annulus (Ea and Aa, respectively), mitral E/Ea ratio (subclinical left ventricular diastolic function), standard deviation of time from ECG Q to systolic peak velocity of 12 left ventricular segments (Ts-SD12), and maximal difference between peak systolic velocities of any 2 of the 12 segments (Ts-Max). A Ts-SD12 at least 33 or Ts-Max at least 100 ms was regarded as presence of LVSD. Results: Patients were divided into those without LVSD (group 1, n = 151, 56.8%) and those with LVSD (group 2, n = 115, 43.2%). Group 2 had higher E/Ea and high-density lipoprotein and lower Sa and triglyceride than group 1. On multivariate analysis, Sa was independently and inversely associated with the presence of LVSD [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.48–0.93, P = 0.018]. The linear relationship between variables and degree of LVSD showed that serum potassium levels, E/Ea, and Sa remained significant after multivariate analysis (potassium, &bgr; = 0.199, P = 0.006; E/Ea, &bgr; = 0.211, P = 0.017; Sa, &bgr; = −0.301, P < 0.001 in Ts-SD12 and potassium, &bgr;=0.187, P = 0.010; E/Ea, &bgr; = 0.234, P = 0.008; Sa, &bgr; = −0.322, P < 0.001 in Ts-Max, respectively). Conclusion: Subclinical left ventricular systolic function is independently associated with both the presence and degree of LVSD in treatment-naive hypertensive patients. Subclinical left ventricular diastolic function and serum potassium levels are independently associated with the degree of LVSD. However, arterial stiffness and BP parameters are not determinants.

A randomized comparison study assessing the impact of cilostazol on the heart rate and arrhythmias by 24-hour ambulatory holter electrocardiographic monitoring after drug-eluting stent implantation for coronary artery disease.

AIMS Cilostazol may have a positive chronotropic or pro-arrhythmic effect. However, there have been no randomized trials to confirm these effects. METHODS This randomized prospective trial compared dual (DAT, aspirin and clopidogrel, n=114) versus triple antiplatelet therapy (TAT, DAT plus cilostazol, n=113) at baseline and after six months in patients receiving intracoronary drug-eluting stents (DES). The primary endpoint was the 24-hour heart rate (24h-HR) at six months determined using 24h-Holter ECG monitoring. The secondary endpoints were the 24h-HR ≥70 bpm, 24h-HR increase ≥5 bpm and the counts or presence of arrhythmias. RESULTS At six months after DES implantation, the 24h-HR (73 [68-83] vs. 68 [62-75] bpm, p＜0.001), presence of a 24h-HR ≥70 bpm (71.4 vs. 47.1%, p＜0.001) and presence of a 24h-HR increase ≥5 bpm (44.8 vs. 24.5%, p=0.002) were significantly higher for the TAT group than for the DAT group. A multivariate analysis showed that the use of cilostazol (OR: 3.10, p=0.035) and a baseline 24h-HR ＜70 bpm (OR: 4.60, p＜0.001) were strong predictors of a 24h-HR increase ≥5 bpm. However, there were no significant intergroup differences in arrhythmias. CONCLUSIONS Cilostazol appears to result in an increase in the 24h-HR after DES implantation. Therefore, some caution should be exercised regarding the use of cilostazol in patients with tachycardia, when planning DES implantation.

Impact of antihypertensive treatment on left ventricular systolic dyssynchrony in treatment-naïve hypertensive patients

Dyssynchrony is common in asymptomatic patients with hypertension. We sought to investigate the impact of antihypertensive treatment on dyssynchrony in patients with hypertension. A total of sixty patients who had uncomplicated hypertension that had never been treated (treatment-naïve hypertensive patients) underwent echocardiographic evaluations of left ventricular (LV) dyssynchrony at baseline and after a 6-month treatment with antihypertensive drugs. The measured parameters were as follows: (1) the s.d. of 12 LV-segment time-to-peak systolic velocities (Ts-SD12), and (2) the maximal difference between peak systolic velocities of any 2 of the 12 segments (Ts-Max). Patients with Ts-SD12 ⩾33 ms or Ts-Max ⩾100 ms were regarded as having LV systolic dyssynchrony. Patients with systolic dyssynchrony (group 1, n=29) and without systolic dyssynchrony (group 2, n=31) were compared. Among the patients in group 1, antihypertensive treatment significantly improved LV systolic dyssynchrony (ΔTs-SD12, −13.1 ms; P<0.001 and ΔTs-Max, −34.0 ms; P=0.003), whereas it did not demonstrate additional benefit among group 2 patients. The change in LV systolic dyssynchrony was significantly associated with changes in the mean annulus E′ velocity, mean annulus S′ velocity and mean annulus E′/A′ ratio, but not with changes in blood pressure and LV mass index. It is likely that chronic antihypertensive treatment could reverse the LV systolic dyssynchrony and simultaneously improve subclinical systolic and diastolic function in patients with hypertension and LV systolic dyssynchrony.

Clinical implications of combined glucose intolerance in treatment-naïve hypertensive patients

ABSTRACT Background: This study is the first study to evaluate clinical significance of combined glucose intolerance (CGI) in treatment-naïve hypertensive patients. Methods: We compared the results of demographic, anthropometric, clinical, laboratory examinations, echocardiography, arterial stiffness, central blood pressure (BP) and ambulatory BP monitoring (ABPM) between the groups according to fasting blood sugar (FBS), postprandial 2 hour blood glucose (PP2) and gender in treatment-naïve hypertensive patients. A total of 376 concecutively-eligible patients were categorized as follows: (1) normal glucose tolerance (NGT); FBS<100 mg/dL and PP2 < 140 (2) isolated glucose intolerance (IGI); 100≤FBS<126 or 140≤PP2 < 200, but not both 100≤FBS<126 and 140≤PP2 < 200 (3) CGI; both 100≤FBS<126 and 140≤PP2 < 200. Results: Males were divided into NGT (n = 58, 33.1%), IGI (n = 88, 50.3%), CGI (n = 29, 16.6%) and females were divided into NGT (n = 59, 43.1%), IGI (n = 48, 35%), CGI (n = 30, 21.9%). In males multivariate analyses revealed that mitral average E/Ea (IGI vs CGI, p = 0.022), brachial-ankle pulse wave velocity baPWV(Rt.) (IGI vs CGI, p = 0.026), baPWV(Lt.) (IGI vs CGI, p = 0.018), office systolic BP (SBP) (NGT vs. CGI, p = 0.005; IGI vs. CGI, p = 0.001), office diastolic BP (DBP) (NGT vs. CGI, p = 0.034; IGI vs. CGI, p = 0.019), night-time SBP (NGT vs. CGI, p = 0.049; IGI vs. CGI, p = 0.018) were significantly higher in the CGI group than in the NGT or IGI group. However, there were no significant differences between the female groups. Conclusions: Treatment-naïve hypertensive males with CGI revealed subclinical diastolic dysfunction, arterial stiffness, and BPs.