Jong-Hoa Bae

A case of systemic amyloidosis following ankylosing spondylitis associated with congestive heart failure.

Secondary (amyloid A [AA]) amyloidosis is a systemic disease characterized by amyloid deposition in many organs, leading to impaired function. Although cardiac involvement may occur with AA amyloidosis, significant deposition of amyloid in the heart is considered an infrequent observation and is rarely the cause of death. It occurs in 5% of patients with poorly controlled chronic inflammatory disease, mainly rheumatoid arthritis, ankylosing spondylitis, and familial Mediterranean fever. The authors report a case of AA amyloidosis diagnosed by rectal and skin biopsies, with cardiac involvement demonstrated by typical echocardiographic features in the presence of low voltage on electrocardiography.

Acute regional myocarditis with normal ventricular wall motion diagnosed by two-dimensional speckle tracking imaging.

To the Editor, Acute myocarditis associated with a normal left ventricular (LV) ejection fraction is challenging to diagnose. Echocardiography is the initial imaging modality used, but diagnostic accuracy is limited, especially in patients with chest pain in whom LV function and size are almost always normal [1]. The current reference standard for noninvasive diagnosis of myocarditis is cardiac magnetic resonance (CMR) imaging [2]. Here we describe a case of a 19-year-old man who presented with severe chest pain that mimicked acute coronary syndrome but was subsequently diagnosed with acute regional myocarditis by two-dimensional (2D) speckle echocardiography. The patient was successfully treated medically for myocarditis. A 19-year-old male with no cardiovascular risk factors was admitted due to chest discomfort and fever. On admission, blood pressure, heart rate and body temperature were 140/65 mmHg, 92 beats per minute, and 38℃, respectively. Initial electrocardiography showed upwardly concave ST elevations in II, III, and aVF leads, with no reciprocal change in the anterior chest lead. Laboratory tests revealed elevated serum C-reactive protein (CRP) and cardiac biomarker (CRP, 1.5 mg/L; creatine kinase [CK], 616 IU/L; CK-MB, 53.0 IU/L; and troponin-I, 4.81 ng/mL). A 2D-echocardiogram showed normal regional wall motion with preserved LV systolic and diastolic function, but automated function imaging, which was assessed by a 2D speckle-tracking imaging (STI), showed a decreased peak in the systolic longitudinal strain of the basal inferior and lateral walls (Fig. 1D, Bulls eye view) and the circumferential strain also decreased in the basal inferior and lateral walls (Fig. 2). Strain curves showed that abnormal longitudinal systolic shortening was detected by strain echocardiography in the lateral and posterior wall, where there were abnormalities indicating longitudinal strain such as a reduced systolic shortening and a postsystolic peak (Fig. 1A, yellow line; Fig. 1B, red line); however, longitudinal systolic shortening in the anterior, inferior and septal walls was normal (Fig. 1C). This pattern was also observed in the circumferential strain curve (Fig. 2). Elevated cardiac biomarkers and decreased regional peak systolic strain usually suggest regional coronary ischemia. However, in this patient, ischemic disease was extremely unlikely due to his young age, lack of family history of coronary artery disease, and lack of regional wall motion abnormalities on the conventional 2D echocardiogram, despite a decreased regional peak longitudinal strain. Therefore, conservative treatment was initiated, including pain medications and diuretics, rather than invasive procedures such as a coronary angiography or myocardial biopsy. To confirm the diagnosis and to examine the change in the myocardium, CMR imaging was performed on the day following admission. Gadolinium-enhanced CMR on the fifth day of admission demonstrated subepicardial delayed hyperenhancement at the basal inferior, lateral wall and the mid lateral wall on short axis, 10 minutes after the enhancement of the image in accordance with myocarditis (Fig. 3). Surprisingly, abnormalities in automated functional imaging and strain curve analysis correlate closely with findings on CMR imaging. Antigen tests for cosackie and influenza viruses were positive. With the suspicion of acute viral myocarditis associated with influenza, we prescribed tamiflu (Genentech, Basel, Switzerland) for 5 days. The patients clinical signs resolved along with the normalization of the ST segment changes and the serum CK level. Figure 1 Two-dimensional speckle tracking imaging. Strain curves showed that abnormal longitudinal systolic shortening was detected by strain echocardiography in the lateral and posterior wall, where there were abnormalities indicating longitudinal strain such ... Figure 2 Two-dimensional segmental circumferential strain curves and color M mode depicting attenuated strain in inferior and lateral segments at the mid-ventricular level. Figure 3 (A, B) Cardiac magnetic resonance imaging showed subepicardial delayed hyperenhancement at the basal inferior, lateral, and mid lateral walls on short axis on a 10 minute-delayed enhancement image. Acute myocarditis has myriad presentations, and often mimics acute coronary syndrome at initial presentation. CMR imaging and myocardial biopsy at the initial acute presentation is not feasible for a differential diagnosis and cannot confirm myocarditis. However, conventional 2D echocardiography, plus strain imaging were crucial in this case to determine the best course of treatment. This case demonstrated that decreased myocardial strain as assessed by 2D speckle echocardiography and different strain curve pattern such as reduction in systolic shortening and postsystolic peak may lead clinicians to the accurate diagnosis of acute myocarditis in patients with chest pain and elevated cardiac biomarkers, but normal wall motion, mimicking acute coronary syndrome. Although the diagnosis of myocarditis has traditionally required a histologic diagnosis, according to the classic Dallas criteria, new diagnostic strategies such as CMR can strongly indicate and diagnose myocarditis. CMR imaging can characterize tissue according to water content and changes in contrast kinetics, which allows visualization of the entire myocardium. Thus, it is well suited to detect patchy myocarditic lesions [3]. Recently, CMR imaging has become the noninvasive diagnostic tool of choice to diagnose myocarditis, and is recommended in patients whose symptoms suggest this condition [2]. However, CMR does have some disadvantages, notably its high cost and the time needed to perform it; therefore, it is not feasible in an acute emergency setting. Conventional 2D echocardiography has traditionally played a limited role in the diagnostic armamentarium for acute myocarditis due to the lack of specific distinguishing features and/or apparently normal examinations encountered in less severe forms of myocarditis [1]. Nevertheless, segmental and global wall motion abnormalities do occur, and patterns of hypertrophic, dilated, and restrictive cardiomyopathy have been reported in histologically proven myocarditis [1]. The advent of novel echocardiographic modalities, such as strain echocardiography, has dramatically expanded the scope of echocardiography, which provides an accurate bedside assessment of regional contractility and can identify longitudinal myocardial dysfunction derived from edema in acute myocarditis [4,5]. Particularly for myocardial damage of only the epicardial layer of the ventricular wall during acute myocarditis, Doppler echocardiography can identify longitudinal segmental myocardial dysfunction derived from edema [5]. These newer techniques are more efficacious than conventional echocardiography in the diagnosis of myocarditis. Interestingly, decreased myocardial longitudinal strain and circumferential strain assessed by the 2D speckle tracking technique, in the absence of wall motion abnormalities, may represent a useful additional diagnostic finding in acute regional myocarditis, while longitudinal segmental myocardial dysfunction derived from edema also supports the diagnosis. This methodological improvement allowed us to evaluate myocardial damage using CMR rather than subjecting the patient to invasive methods such as coronary angiography. In conclusion, in young patients with chest pain who have elevated cardiac biomarkers and dynamic EKG changes but who do not fit the signalment for coronary disease, 2D STI analysis, including longitudinal and circumferential strain, can help physicians to diagnose acute myocarditis and to devise an appropriate treatment plan.

An open-label, uncontrolled, 8-week clinical trial of barnidipine hydrochloride, a once-daily calcium channel blocker, in Korean patients with essential hypertension

Abstract The efficacy and tolerability of barnidipine hydrochloride, a once-daily calcium channel blocker, was investigated in 31 Korean patients (19 women and 12 men; mean age, 53 ± 8 years; mean body weight, 65.8 ± 9.1 kg) with essential hypertension (mean systolic blood pressure [SBP] and diastolic blood pressure [DBP] in the sitting position, 154.5 ± 15.9 mm Hg and 101.0 ± 8.2 mm Hg, respectively). This study used an increasing-dose method with daily doses of 5 to 15 mg in an open-label, uncontrolled manner for 8 weeks. Mean reductions in SBP and DBP after 8 weeks of treatment with barnidipine were 28.5 mm Hg (mean reduction, 18.4%) and 16.5 mm Hg (mean reduction, 16.3%) in the sitting position, respectively, and the mean dose was 9.7 mg/d. Heart rate in the sitting position was not changed by the administration of barnidipine (mean ± SD, 70.0 ± 6.6 beats/min and 71.9 ± 6.8 beats/min before and after treatment, respectively). Barnidipine was well tolerated, with only mild adverse events such as headache (appearance rate, 6.5%), facial flushing (6.5%), dizziness, nausea, and vomiting (each, 3.2%). These results suggest that barnidipine is a once-daily calcium channel blocker that shows sufficient hypotensive effect and good tolerability in Korean patients with essential hypertension.

A case of concentric left ventricular hypertrophy with falsely normal blood pressure in patient with Takayasu’s arteritis

This is a case of full-blown Takayasu’s arteritis in a young woman complicated with recurrent strokes, which was diagnosed late, after echocardiographic examination identifying concentric left ventricular hypertrophy of unknown cause and falsely normal blood pressure due to arterial stenoses in all four limbs. Herein we describe this interesting and instructive case with a short review of literature.

1018 Genetic Influences on the pharmacokinetic and pharmacodynamic characteristics of valsartan

Background: Valsartan is an angiotensin II AT1 receptor blocker and is used for patient with hypertension. To investigate genetic factors affecting the pharmacokinetics (PK) and pharmacodynamics (PD) of valsartan, single group, open label and pre- and post-comparison clinical study was conducted. Methods: Total 21 male Korean volunteers were enrolled. Each subject was administered placebo in first period and valsartan 80 mg (Diovan®) in second period. For PD analysis, 24-hr blood pressure changes were monitored. For determination of valsartan in human plasma, rapid and sensitive high-performance liquid chromatography- electrospray ionization tandem mass spectrometric method was used. For genetic analysis, we used Illumina Human610Quad v1.0 DNA Analysis BeadChip for whole genome SNPs analysis. Patients were divided into two groups according to PK and PD parameters. PK parameters were Cmax, AUCt, AUCinf, and Tmax. Diurnal BP pattern change after medication was used as a PD parameter (drug responder vs. non-responder). Whole genome genotyping data was processed by linear regression analysis for PK and PD parameters. Results: Drug responders had greater drug absorption pattern than non-responders. Functional locations of SNPs were mainly located on the flanking 5′UTR, intron and flanking 3′UTR. Significant SNPs in the PK and PD parameters were related to signaling pathways including calcium, MAPK and vascular smooth muscle contraction. Conclusion: Several significant SNPs affect the ADME (absorption-distribution-metabolism-excretion) and the PD differences of valsartan. Identified significant SNPs will help understanding of individual differences in responsiveness of valsartan.

482 PLASMA RENIN-GUIDED TREATMENT IN YOUNG UNTREATED HYPERTENSION: A RANDOMIZED COMPARATIVE PILOT STUDY

Background: Renin–guided therapeutics using plasma renin activity (PRA) values may lead to clinically significant blood pressure (BP) reductions. We were to compare the effect of renin-guided therapy versus routine practice in young untreated hypertensive patients who mostly have high renin activity would benefit from renin-targeted antihypertensive drugs. Methods: Thirty-two young untreated hypertensive patients less than 55 years old were randomized to either renin-guided group (PRA group, n = 16) or routine practice (Control group, n = 16) in hypertension clinic. After the blood samples for PRA were drawn at the first visit, randomization was made after one week. PRA group received antihypertensive drug based on their PRA, i.e. either angiotensin converting enzyme inhibitor or angiotensin receptor blocker if their PRA ≥0.65 ng/ml/h, calcium antagonist or diuretics if PRA < 0.65 ng/ml/h. Control group received antihypertensive drug selected by a specialist blinded to PRA value. If the BP has not reached the goal (<140/90mmHg) after 2 months, both group received another class of antihypertensive drugs added. Results: The study subjects were 45 years old in average (from 33 to 54). PRA group had similar initial BP (systolic BP, 156.8 ± 14.5 vs 166.9 ± 18.2 mmHg; diastolic BP, 97.7 ± 10.7 vs. 102.9 ± 12.3 mmHg) and showed similar BP reduction after one year study period (systolic BP, 126.2 ± 9.4 vs 128.0 ± 10.5 mmHg; diastolic BP, 80.8 ± 6.1 vs 78.4 ± 7.2 mmHg) compared to Control group. Conclusion: Plasma renin-guided treatment in young untreated hypertension does not seem to be more effective for the short-term BP reduction than the routine practice independent of PRA value.

853 ANGIOTENSIN II RECEPTOR BLOCKER IMPROVES THE PATTERN OF NOCTURNAL DIPPING IN UNTREATED HYPERTENSIVES

Background: Nocturanl blood pressure (BP) decrease less than 10% is known as a nondipping BP pattern. Nondipping BP has been shown to be associated with target organ damage and poorer cardiovascular outcomes. It was suggested that the angiotensin II receptor blockers (ARBs) could improve nocturnal dipping by enhancing daytime sodium excretion. We elucidated the effects of ARBs and calcium channel blockers (CCBs) on 24-hour ambulatory BP monitoring (ABPM) in untreated hypertensives. Method: Fifty patients with untreated hypertension (male:female = 30:20; mean age 51 ± 14 years; the mean duration of medication 344 days) were examined by ABPM before and after antihypertensive medication. We divided those patients into two groups [CCB group treated with CCBs (male:female = 9:11; mean age = 53 ± 15 years) and ARB group treated with ARBs (male:female = 21:9; mean age = 49 ± 13 years)]. The &Dgr; dipping was defined to [nocturnal BP decrease (%) after medication] – [nocturnal BP decrease (%) before medication]. Result: There were no significant differences in the clinical characteristics between two groups. The follow up nocturnal systolic and diastolic BP decrease were significantly smaller in CCB group than in ARB group (9.07 ± 10.16 vs. 14.33 ± 6.73, p = 0.032 in systolic BP; 10.12 ± 9.77 vs. 16.54 ± 6.63, p = 0.008 in diastolic BP). The &Dgr; dipping was significantly smaller in CCB group than in ARB group (-1.46 ± 7.44 vs. 4.13 ± 7.99, p = 0.018 in systolic BP; -2.81 ± 7.78 vs. 5.11 ± 8.64, p = 0.002 in diastolic BP). Conclusions: ARBs can effectively improve nocturnal dipping in untreated hypertension.

V-012 RENIN-GUIDED VERSUS ROUTINE TREATMENT IN YOUNG UNTREATED HYPERTENSION: A RANDOMIZED COMPARATIVE PILOT STUDY

Background Renin–guided therapeutics using plasma renin activity (PRA) values may lead to clinically significant blood pressure (BP) reductions. We were to compare the effect of renin-guided therapy versus (not renin-based) routine practice on short-term BP reductions in young untreated hypertensive patients who mostly have high renin activity would benefit from renin-targeted antihypertensive drugs. Methods Thirty-two young untreated hypertensive patients less than 55 years old were randomized to either renin-guided group (PRA group, n = 16) or routine practice (Control group, n = 16) managed by different specialists in hypertension clinic. After the blood samples for PRA were drawn at the first visit, randomization was made after one week. PRA group received antihypertensive drug based on their PRA, i.e. either angiotensin converting enzyme inhibitor or angiotensin receptor blocker if their PRA ≥0.65 ng/ml/h, calcium antagonist or diuretics if PRA< 0.65 ng/ml/h. Control group received antihypertensive drug selected by a specialist blinded to PRA value. If the BP has not reached the goal (<140/90mmHg) after 2 months, both group received another class of antihypertensive drugs added. Results PRA group showed similar BP reduction after one year study period (systolic BP, 126.2 ± 9.4 vs 128.0 ± 10.5 mmHg; diastolic BP, 80.8 ± 6.1 vs 78.4 ± 7.2 mmHg) compared to Control group. Figure. No caption available. Conclusions Plasma renin-guided treatment in young untreated hypertension does not seem to be more effective for the short-term BP reduction than the routine practice.

RELATION OF ABDOMINAL OBESITY, METABOLIC RISK FACTORS, AND LEFT VENTRICULAR HYPERTROPHY IN HEALTHY MIDDLE-AGED AND OLDER MEN: PP.28.121

Background: Obese individuals are likely to have a high burden of subclinical disease and at increased risk of development of overt cardiovascular disease (CVD). We were to determine the relationships between abdominal obesity, other metabolic risk factors, and electrocardiographic left ventricular hypertrophy (ECG-LVH) in healthy Asian middle aged and older men who have different anthropometric habitus from westerners. Methods: Healthy 251 men who visited for a general health examination and free from overt medical illness were enrolled. Sixty-five men (25.9%) with waist circumference (WC) ≥90 cm were compared with 186 men with WC <90 cm. Results: Men with increased WC had increased prevalence of traditional risk factors and higher prevalence of increased fasting plasma insulin, insulin resistance, and metabolic syndrome and decreased insulin sensitivity. WC increased substantially as the numbers of elements of metabolic syndrome. Men with increased WC had higher Cornell voltage, and Cornell voltage product. Conclusion: The metabolic risk factors and ECG-LVH are prevalent in healthy Asian middle-aged and older men with abdominal obesity. Thus routine measurement of WC and simple ECG may reflect subclinical CVD and predict obesity-related health risk. Figure 1. No caption available.