Lipid-Lowering Efficacy of Combination Therapy With ModerateIntensity Statin and Ezetimibe Versus High-Intensity Statin Monotherapy:A Randomized, Open-Label, NonInferiority Trial From Korea

Objective@#This phase IV, multicenter, randomized controlled, open-label, and parallel clinical trial aimed to compare the efficacy and safety of ezetimibe and moderate intensity rosuvastatin combination therapy to that of high intensity rosuvastatin monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). @*Methods@#This study enrolled patients with ASCVD and after a four-week screening period, patients were randomly assigned to receive either rosuvastatin and ezetimibe (RE 10/10 group) or high-intensity rosuvastatin (R20 group) only in a 1:1 ratio. The primary outcome was the difference in the percent change in the mean low-density lipoprotein cholesterol (LDL-C) level from baseline to 12 weeks between two groups after treatment. @*Results@#The study found that after 12 and 24 weeks of treatment, the RE10/10 group had a greater reduction in LDL-C level compared to the R20 group (−22.9±2.6% vs. −15.6 ± 2.5% [p=0.041] and −24.2±2.5% vs. −12.9±2.4% [p=0.001] at 12 and 24 weeks, respectively). Moreover, a greater number of patients achieved the target LDL-C level of ≤70 mg/dL after the treatment period in the combination group (74.6% vs. 59.9% [p=0.012] and 76.2% vs. 50.8% [p<0.001] at 12 and 24 weeks, respectively). Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between two groups. @*Conclusion@#Moderate-intensity rosuvastatin and ezetimibe combination therapy had better efficacy in lowering LDL-C levels without increasing adverse effects in patients with ASCVD than high-intensity rosuvastatin monotherapy.

Effect of body mass index and abdominal obesity on mortality after percutaneous coronary intervention: a nationwide, population-based study

Background/Aims@#We investigated the impact of obesity on the clinical outcomes following percutaneous coronary intervention (PCI). @*Methods@#We included South Koreans aged > 20 years who underwent the Korean National Health Screening assessment between 2009 and 2012. Obesity was defined using the body mass index (BMI), according to the World Health Organization’s recommendations. Abdominal obesity was defined using the waist circumference (WC), as defined by the Korean Society for Obesity. The odds and hazard ratios in all-cause mortality were calculated after adjustment for multiple covariates. Patients were followed up to the end of 2017. @*Results@#Among 130,490 subjects who underwent PCI, the mean age negatively correlated with BMI. WC, hypertension, diabetes, dyslipidemia, fasting glucose, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels correlated with the increased BMI. The mortality rates were higher in the lower BMI and WC groups than the higher BMI and WC groups. The non-obese with abdominal obesity group showed a mortality rate of 2.11 per 1,000 person-years. Obese with no abdominal obesity group had the lowest mortality rate (0.88 per 1,000 person-years). The mortality showed U-shaped curve with a cut-off value of 29 in case of BMI and 78 cm of WC. @*Conclusions@#The mortality showed U-shaped curve and the cut-off value of lowest mortality was 29 in case of BMI and 78 cm of WC. The abdominal obesity may be associated with poor prognosis in Korean patients who underwent PCI.

Impact of Hospital Volume of Percutaneous Coronary Intervention (PCI) on In-Hospital Outcomes in Patients with Acute Myocardial Infarction: Based on the 2014 Cohort of the Korean Percutaneous Coronary Intervention (K-PCI) Registry

Background and Objectives@#The relationship between the hospital percutaneous coronary intervention (PCI) volumes and the in-hospital clinical outcomes of patients with acute myocardial infarction (AMI) remains the subject of debate. This study aimed to determine whether the in-hospital clinical outcomes of patients with AMI in Korea are significantly associated with hospital PCI volumes. @*Methods@#We selected and analyzed 17,121 cases of AMI, that is, 8,839 cases of non-ST-segment elevation myocardial infarction and 8,282 cases of ST-segment elevation myocardial infarction, enrolled in the 2014 Korean percutaneous coronary intervention (K-PCI) registry. Patients were divided into 2 groups according to hospital annual PCI volume, that is, to a high-volume group (≥400/year) or a low-volume group (<400/year). Major adverse cardiovascular and cerebrovascular events (MACCEs) were defined as composites of death, cardiac death, non-fatal myocardial infarction (MI), stent thrombosis, stroke, and need for urgent PCI during index admission after PCI. @*Results@#Rates of MACCE and non-fatal MI were higher in the low-volume group than in the high-volume group (MACCE: 10.9% vs. 8.6%, p=0.001; non-fatal MI: 4.8% vs. 2.6%, p=0.001, respectively). Multivariate regression analysis showed PCI volume did not independently predict MACCE. @*Conclusions@#Hospital PCI volume was not found to be an independent predictor of in-hospital clinical outcomes in patients with AMI included in the 2014 K-PCI registry.

Dyslipidemia and Rate of Under-Target Low-Density Lipoprotein-Cholesterol in Patients with Coronary Artery Disease in Korea

OBJECTIVE: The aim of this study was to evaluate under target rates of low-density lipoprotein-cholesterol (LDL-C) in Korean patients with stable coronary artery disease (CAD) or an acute coronary syndrome (ACS) in real world practice. METHODS: Dyslipidemia International Study II was an international observational study of patients with stable CAD or an ACS. Lipid profiles and use of lipid-lowering therapy (LLT) were documented at enrollment, and for the ACS cohort, 4 months follow-up was recommended. Rates of under target LDL-C as per European guidelines, were evaluated, and multivariate regression was performed to identify predictive factors of patients presenting under the target. RESULTS: A total of 808 patients were enrolled in Korea, 500 with stable CAD and 308 with ACS. Of these, 90.6% and 52.6% were being treated with LLT, respectively. In the stable CAD group, 40.0% were under target LDL-C, while in ACS group, the rate was 23.7%. A higher statin dose was independently associated with under target LDL-C in both groups (OR, 1.03; p=0.046 [stable CAD] and OR, 1.05; p=0.01 [ACS]). The mean statin dosage (atorvastatin equivalent) was 17 mg/day. In the 79 ACS patients who underwent the follow-up examination, the LDL-C under target rate rose to 59.5%. CONCLUSION: Only a minority of patients with stable CAD or ACS were under their target LDL-C level at enrollment. The statin dose was not sufficient in the majority of patients. These results indicate a considerable LLT gap in Korean patients with established CAD.

A Case of Acquired Coronary-Cameral Fistulae / 대한내과학회지

We report a rare case of acquired multiple coronary-cameral fistulae. A 46-year-old man presented to the cardiology department clinic complaining of recently aggravated exertional chest pain. He had been treated 10 years ago for an acute ST segment elevation myocardial infarction (STEMI) with percutaneous coronary intervention (PCI). During revascularization, diffuse multiple fistulae from the left anterior descending (LAD) artery to the left ventricle (LV) had been observed. The current chest pain was evaluated by elective coronary angiography but no significant stenosis was observed. However, newly developed diffuse fistulae from the distal right coronary artery (RCA) to LV were found during angiography, as well as LAD-LV coronary fistulae. Multiple coronary-cameral fistulae were thought to be causing chest pain. A beta-blocker was prescribed and, after 3 months of follow-up, exertional chest pain had subsided without further complication.

Retrieval of a Partially Degloved Stent Strut During Percutaneous Coronary Intervention / 전남의대학술지

Although stent entrapment is a rare event during percutaneous coronary intervention, stent entrapment can cause stent breakage or loss, which results in fatal complications such as stent embolism or acute myocardial infarction. We report one case of stent entrapment that was successfully treated by a snare via a contralateral transfemoral approach.

Phantom Ischemia Mimicking ST Segment Elevation Myocardial Infarction in Fulminant Myocarditis / 이화의대지

A 30-year-old man visited the emergency room for chest pain, dyspnea and fever. Despite increased serum cardiac enzymes, ST segment elevation and inferior wall akinesis in electrocardiography and echocardiography, no atherosclerosis was evident in the coronary angiography. However, radionuclide myocardial perfusion image at day 2 showed a persistent perfusion defect in the left ventricular (LV) inferior wall. At day 3, prominent myocardial edema and severe LV systolic dysfunction developed with signs of heart failure. In this case, fulminant myocarditis seemed to originate from the right coronary artery territory and simulated a ST segment elevation myocardial infarction without coronary artery obstruction. The pathogenesis of the localized perfusion defect was unlcear.

Retrieval of a Partially Degloved Stent Strut During Percutaneous Coronary Intervention / 전남의대학술지

Although stent entrapment is a rare event during percutaneous coronary intervention, stent entrapment can cause stent breakage or loss, which results in fatal complications such as stent embolism or acute myocardial infarction. We report one case of stent entrapment that was successfully treated by a snare via a contralateral transfemoral approach.

A Case of a Zotarolimus-Eluting Stent Fracture in the Left Anterior Descending Artery in a Patient Undergoing Hemodialysis / 전남의대학술지

Although stent fracture after implantation of a drug-eluting stent (DES) is a rare complication, it has been suggested to be a cause of restenosis. To date, most DES fractures have been associated with sirolimus-eluting stents. We describe here a case of a zotarolimus-eluting stent fracture after 8 months of stent placement in a calcified left anterior descending artery lesion in a patient undergoing hemodialysis.

A Case of a Zotarolimus-Eluting Stent Fracture in the Left Anterior Descending Artery in a Patient Undergoing Hemodialysis / 전남의대학술지

Although stent fracture after implantation of a drug-eluting stent (DES) is a rare complication, it has been suggested to be a cause of restenosis. To date, most DES fractures have been associated with sirolimus-eluting stents. We describe here a case of a zotarolimus-eluting stent fracture after 8 months of stent placement in a calcified left anterior descending artery lesion in a patient undergoing hemodialysis.

Simultaneous Multi-Vessel Subacute Stent Thromboses in Zotarolimus-Eluting Stents

Despite its low incidence, stent thrombosis (ST) is one of the most dreaded complications of percutaneous coronary intervention. Endeavor (Medtronics Europe SA) is a new zotarolimus-eluting stent (ZES) with a favorable safety profile that was reported in early and ongoing trials. However, few lethal stent thromboses related to this new drug eluting stent (DES) have been reported. We experienced a case of simultaneous subacute ZES thromboses, 6 days after stent implantations in the proximal left anterior descending artery and the proximal right coronary artery (RCA).

Effect of Human Bcl-2 Gene Expression on the Peripheral Atherosclerotic Lesions of Apolipoprotein E-Deficient Mouse

BACKGROUND AND OBJECTIVES: Bcl-2 protein is related to the inhibition of apoptosis via the mitochondrial pathway and Bcl-2's anti-oxidant effect. During the development of atherosclerosis, apoptosis is known to play an important role in the pathophysiologic behavior of atherosclerotic vascular disease in the medium-sized arteries. Apoptosis may be a compensatory reaction to regulate the cellular density of various tissues during the cellular proliferation process such as happens with tissue injury and during the development of atherosclerosis. The consequences of apoptosis in atherosclerosis may be related to the formation of an acellular lipid core, plaque instability and the loss of vascular wall integrity and remodeling. We sought to determine the effect of Bcl-2 gene expression on the development of primary atherosclerosis in apolipoprotein E deficient mouse, which is one of the typical animal models that are used for the development of peripheral atherosclerosis. MATERIALS AND METHODS: Bcl-2 transgenic mice were cross hybridized with apolipoprotein E deficient mice. Systemic analysis of the distribution and severity of their atherosclerotic lesions was done by dissecting microscopy, and the histological characteristics of the lesions were evaluated in normal chow-fed, 9-month-old apolipoprotein-E deficient/Bcl-2 transgenic mice (n=6) and apolipoprotein-E deficient mice (n=6). RESULTS: The distribution and severity of atherosclerotic lesions at the peripheral arteries were less in the apolipoprotein-E deficient/Bcl-2 transgenic mice. Acellular lipid core formation, destruction of the smooth muscle cell layers in the media and infiltration of inflammatory cells in the adventitia were much less in the apolipoprotein-E deficient/Bcl-2 transgenic mice. The lipid profile was similar in both groups. CONCLUSION: The effect of Bcl-2 gene expression on the peripheral atherosclerosis was related with the inhibition or the delay of atherosclerotic lesion progression, such as the reduction of amount of the acellular lipid core, maintenance of vascular smooth muscle cell integrity and the reduction of adventitial inflammation, and this was achieved regardless of serum cholesterol level.

Effects of Cilostazol on Platelet Activation in Coronary Stenting Patients Who Already Treated with Aspirin and Clopidogrel

BACKGROUND: A recent study has shown that triple anti-platelet therapy (cilostazol+clopidogrel+aspirin) resulted in a significantly lower restenosis rate after coronary stenting than did conventional therapy (clopidogrel+aspirin). However, the anti-platelet effects of cilostazol, when combined with clopidogrel and aspirin, have not been evaluated. METHODS: Low dose cilostazol (50 mg/BID) was given to 47 patients who had already been taking clopidogrel (75 mg/day) and aspirin (100 mg/day) for more than 1 month subsequent to coronary stenting due to AMI and unstable angina. Markers of platelet activation, P-selectin and activated GPIIb/IIIa on platelets, were measured at baseline and 2 weeks after cilostazol treatment. We empirically divided patients into tertiles (low, n=16; moderate, n=14; high group, n=17), according to the baseline P-selectin expression. We then performed a comparative assessment of the anti-platelet effects of cilostazol at baseline and after 2 weeks of cilosatzol administration. RESULTS: P-selectin was significantly decreased after 2 weeks of cilostazol treatment in total patients (n=47, 3.2 +/- 2.4% to 2.0 +/- 1.9%, p=0.03). This inhibition of P-selectin expression was mainly achieved in the moderate and high P-selectin groups (low group; 1.4 +/- 0.5 to 1.9 +/- 1.3%, p> 0.05, moderate group; 2.5 +/- 0.3 to 1.3 +/- 0.3%, p 0.05). Underlying disease, cardiovascular risk factors, concomitant medication including statin, and hsCRP were not related to the degree of P-selectin expression. CONCLUSION: Our data demonstrated that cilostazol treatment in addition to conventional anti-platelet therapy provides more effective suppression of platelet P-selectin expression in patients with relatively high platelet activity.

Relation between Pulse Wave Velocity, Left Ventricular Diastolic Function, and Circadian Variation of Blood Pressure in Patients with Never Treated Essential Hypertension

BACKGROUND AND OBJECTIVES: An increased pulse wave velocity (PWV) and a non-dipping pattern in hypertensive patients have been shown to be associated with an excess of target organ damage. The relationship between the PWV and circadian variation of blood pressure (BP) (dipper or nondipper) were sought, and also the LV diastolic function between dipper and nondipper patients compared. SUBJECTS AND METHODS: 44 hypertensive subjects, who had never been treated, were enrolled (mean age: 48+/-12 yrs, men: 29). The following procedures were undertaken. 1) 24 hour ambulatory BP monitoring; 2) echocardiography for LV geometry, LV mass index (LVMI), LV systolic and diastolic functions, including tissue Doppler and aortic PWV. The patients were divided into two groups with respect to their ambulatory BP profiles, i.e., dipper and nondipper. The PWV, LV geometry and diastolic functions were compared between dipper and nondipper patients, and the relationship between the PWV and diastolic function analyzed in all patients. RESULTS: Twenty (45%) were nondipper patients. There were no significant differences in the LV geometry, LVMI and PWV between dipper and nondipper patients (PWV; 8.8+/-3.1 vs. 8.6+/-3.3 m/sec, p>0.05). In all patients, the PWV was related to the deceleration time (r=0.34, p=0.03) and the mitral E/A (r=-0.31, p=0.02) and mitral Em/Am ratios obtained by the tissue Doppler echocardiography (r=-0.31, p=0.03). The proportion with diastolic dysfunction was higher in the nondipper than the dipper patients (21 vs. 50%, p<0.01). There was a significant relation between the PWV and Em (r=-0.45, p=0.047) in the nondipper, but not in the dipper. CONCLUSION: Prolonged exposure to high BP (nondipper) was not related with increased aortic stiffness in never treated hypertensive patients. The PWV was closely related with LV diastolic dysfunction in nondipper patients.

Structural and Functional Changes of Heart after Cardioversion of Atrial Fibrillation

BACKGROUND AND OBJECTIVES: Chronic atrial fibrillation (AF) causes atrial enlargement and impairs cardiac function. It is known that restoration of sinus rhythm reduces left atrial size and improves left ventricular ejection fraction (EF). However, it's unclear whether the restoration of sinus rhythm is more beneficial than controlling the ventricular rate. This study was designed to compare the effects of two treatment strategies on structural and functional changes of the heart in patients with AF. SUBJECTS AND METHODS: Thirty-seven AF patients who initially cardioverted to sinus rhythm were studied. At 6 months after cardioversion, 17 patients (Group I) maintained normal sinus rhythm (NSR) and 20 (Group II) experienced AF recurrence. Initial and follow-up echocardiography were evaluated in each patient and compared between the two groups. RESULTS: Baseline clinical and echocardiographic findings were similar between the two groups except that the left atrial length was longer in Group II than in Group I. Compared to baseline, left atrial dimension (LAD) and left ventricular mass index (LVMI) measured by M-mode were significantly reduced in group I at follow-up (p<0.05); however, these changes were not observed in group II. The reduction of LAD and LVMI was observed only in patients with less than 50% EF and/or dilated left atrium at baseline (p<0.05). CONCLUSION: In patients with AF, maintenance of NSR after cardioversion significantly reduces LAD and LVMI, especially in cases of left ventricular dysfunction or dilated left atrium. Even after adjustment of baseline LAD, LVMI and EF, maintenance of NSR remains the independent factor that reduces LAD at follow-up (p=0.001).

Pulmonary Embolism after Percutaneous Vertebroplasty with Polymethylmethacrylate: Case Report

We present a case with rare complication of percutaneous vertebroplasty with polymethylmethacrylate (PMMA). A pulmonary embolus was detected in a 79-year-old woman with osteoporotic compression fracture after percutaneous verteroplasty. Chest radiography, computed tomography, and ventilation perfusion lung scan con-firmed pulmonary infarction and the presence of PMMA in the pulmonary arteries. She was treated with anticoagulants and responded favorably. Although venous leakage of PMMA has shown to be not uncommon, only a few cases of symptomatic pulmonary embolism have been reported. Adequate preparation of PMMA, optimal injection technique, and confirmation with biplane fluoroscopy are mandatory to minimize this type of complication.

Vessel Size and Long-Term Clinical and Angiographic Outcome after Primary Stenting in Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES: The role of coronary stenting in the treatment of patients with small vessels ( or =3.0 mm. The primary end points were the major adverse cardiac events including death, recurrent myocardial infarction, or target vessel revascularization at follow-up. The incidence of angiographic restenosis (> or = 50% of diameter stenosis) was assessed as a secondary end point. Event-free survival in the small vessel group (less than 3mm of reference vessel diameter) was 62.5% at 23.7+/-13.0 months and 76% in the large vessel group (p<0.001) at 23.5+/-12.0 months. The follow-up angiographic restenosis rate was significantly higher in the small vessel group (61% vs. 32% in the small and large vessel groups, respectively, p=026). CONCLUSION: Acute myocardial infarction patients with small vessels present a higher risk for an adverse outcome following primary stenting.

Relationship between T-wave normalization on exercise ECG and myocardial functional recovery in patients with acute myocardial infarction

BACKGROUND: Several studies suggested that T-wave normalization (TWN) in exercise ECG indicates the presence of viable myocardium. But the clinical implication of this phenomenon in patients with acute myocardial infarction who received proper revascularization therapy was not determined. Precisely the aim of this study was to investigate the relationship between TWN in exercise ECG and myocardial functional recovery after acute myocardial infarction. METHODS: We studied 30 acute myocardial infarction patients with negative T waves in infarct related electrocardiographic leads and who had received successful revascularization therapy. Exercise ECG was performed 10 ~14days after infarct onset using Naughton protocol. Patients were divided into 2 groups according to presence (group I; n=14) or not (group II; n=16) of TWN in exercise ECG. Exercise parameters and coronary angiographic findings were compared between groups. Baseline and follow-up (mean 11 months) regional and global left ventricular function was analyzed by echocardiography. RESULTS: Exercise parameters were similar between groups. There was no difference in baseline ejection fraction and wall motion score between group I and II (EF; 56 +/- 12% vs 52 +/- 11%, p=ns. WMS; 21 +/- 3 vs 23 +/- 4, p=ns) and it was improved at the tenth month by similar magnitude (group I/group II, EF % change = 12 +/- 12% vs 7 +/- 6%, p=ns, WMS % change=6 +/- 6% vs 7+/- 5%, p=ns). The finding of no relation between TWN and functional recovery was observed also when the patients were analysed according to infarct location and presence or absence of Q-waves. CONCLUSION: As the exercise-induced TWN in patients with acute myocardial infarction was not related with better functional recovery of dysfunctional regional wall motion and ejection fraction, TWN does not appear to be an indicator of myocardial viability.

Factors Affecting Coronary Flow Reserve: Measured by Transthoracic Doppler Echocardiography

BACKGROUND AND OBJECTIVES: Coronary flow reserve (CFR) is considered an important index of the functional significance of coronary artery stenosis, but is influenced by several factors, such as left ventricle hypertrophy (LVH), diabetes mellitus (DM), hyperlipidemia and smoking. Measurement of the coronary flow velocity of the left anterior descending coronary artery (LAD) by transthoracic Doppler echocardiography (TTDE) is feasible, and provides reliable information. The purpose of this study was to investigate the relationship between CFR and LVH, DM, hyperlipidemia and hypertension in patients with or without coronary artery disease, and to assess the prominent factors influencing CFR. SUBJECTS AND METHODS: Coronary angiographies were performed in 38 patients to evaluate chest pain. The distal LAD flow velocity was measured by TTDE, and the CFR calculated as a ratio of the hyperemic and baseline mean diastolic velocities. The CFR was compared with clinical, echocardiographic and angiographic parameters. RESULTS: The CFR was similar in patients both with and without hypertension, DM, high LDL-cholesterol levels and low ejection fraction(<40%). The mean CFR was lower in patients with (50% LAD stenosis than in patients with no significant stenosis. The CFR of patients with a left ventricle wall thickness of (12mm was lower than in those without LVH. The multivariate analysis of the aforementioned factors showed that LVH was the factor most influencing to the CFR (p<0.05). CONCLUSION: When using CFR as a functional parameter of LAD stenosis, one should consider LVH as one of the factors attributed to CFR modification.

Does ST-segment depression combined with R wave amplitude change improve the test accuracy of the EKG during exercise testing? / 대한내과학회지

BACKGROUND: Exercise electrocardiogram is the most widely used non-invasive test in those patients suspected of having coronary artery disease. However, sensitivity and specificity of this test are not satisfactory, especially when the exercise induced ST-segment depression is used as a single criterion of myocardial ischemia. Although many investigators have tried to improve diagnostic accuracy with R-wave amplitude change in addition to ST-segment depression, controversy exists whether this new criteria improve the test accuracy for coronary artery disease or not. The purpose of this study is to determine the test accuracy of R-wave amplitude change induced by exercise combined with the conventional ST-segment criterion for myocardial ischemia. METHODS: We reviewed our records of patients who visited to Korea University Anam Hospital with chest pain from January, 1998 to July, 1999. We included 130 patients with chest pain who had a tredmill test followed by a coronary angiography within 2 months. Patients with change in ST-segment depression (delta STD)> or = 1.00 mm and delta STD> or = 1.00 mm with R wave amplitude decrease (-delta R)> or = 1.00 mm in the same lead in any of 12 leads and delta STD> or = 1.00 mm with R wave amplitude increase (+delta R)> or = 1.00 mm in the same lead in any of 12 leads were compared. According to the findings of coronary angiograms, patients were divided into 4 groups ; normal coronary artery group, mild coronary artery stenosis group (> or = 30% to or = 50% to or = 70%). RESULTS: Fifty three patients (40.7%) had normal coronary angiograms and 77 patients (59.3%) had coronary artery stenosis. There was no significant difference in gender and age. But, patients with coronary artery stenosis had more diabetes mellitus, hyperlipidemia, smoking, previous myocardial infarction history and angina during exercise testing than those without coronary artery stenosis. The sensitivity of exercise EKG is significantly decreased when combined with delta R (delta STD, 74.0%, delta STD with -delta R, 45.5%, delta STD with +delta R, 30.0%, p<0.01), but the The test accuracy is delta STD; 73.7%, delta STD with -delta R; 61.5%, delta STD with +delta R; 57.7%. CONCLUSION: When ST-segment depression is combined with R-wave amplitude change as a marker for myocardial ischemia, the specificity is increased, but the test accuracy of exercise EKG is not improved.