Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort.

BACKGROUND: Ala97Ser transthyretin amyloidosis-associated polyneuropathy (ATTRA97S-PN) is a rare form of inherited polyneuropathy, usually manifesting with late-onset (> 50) progressive polyneuropathy. This mutation is mostly prevalent in Taiwanese and Han-Chinese individuals. The aim of this study was to describe the clinical and comprehensive neurophysiological profiles of ATTRA97S-PN in Thai patients. METHODS: The clinical profiles and serial neurophysiologic studies (nerve conduction study (NCS), quantitative sensory test (QST), and comprehensive autonomic function test (AFT)) of symptomatic ATTRA97S-PN patients who had been followed-up at King Chulalongkorn Memorial Hospital during 2010-2020 were retrospectively reviewed. RESULTS: Nine symptomatic patients (55.6 % were male) from four unrelated families were included. All were Thais of mixed Thai Chinese descent. The mean age of onset was 48.3 (32-60) years. The mean age at diagnosis was 54.8 (33-66) years. Three patients developed early-onset (< 40y) polyneuropathy. The mean Neuropathy Impairment Score was 41.33 (10-92) at diagnosis. Sensory (9/9) and autonomic (9/9) neuropathies were more frequent than motor neuropathy (5/9), which appeared in the late stage of disease. Hypoesthesia in the feet, and gastrointestinal autonomic symptoms were frequently reported as the initial symptoms. The course of neuropathy progressed over years to decades. The worsening of neuropathy tended to progress faster once motor nerves were affected in both clinical and neurophysiological aspects. Concurrent cardiac amyloidosis was found in 6/9 patients. NCS showed length-dependent sensorimotor axonal polyneuropathy in 5/9 patients, and median neuropathy at the wrist (mostly bilateral) in 7/9 patients. QST showed abnormalities in the vibratory detection threshold, the cold detection threshold and the heat pain sensation in 8/9, 8/9 and 7/7 tested patients, respectively. AFT results were abnormal in all. The mean composite autonomic severity score was 5 (3-9). CONCLUSIONS: This clinical study is the first of ATTRA97S-PN in Thai patients. The mixed polyneuropathy-cardiopathy phenotype was the most common manifestation. In this cohort, the age of onset was lower, and the course of neuropathy was relatively longer, than that in previous studies. Some patients may develop early-onset polyneuropathy. This mutation has not yet been documented in any population other than Han Chinese-related populations, probably suggesting a founder effect. Further studies are warranted.

CK-MB Activity, Any Additional Benefit to Negative Troponin in Evaluating Patients with Suspected Acute Myocardial Infarction in the Emergency Department.

BACKGROUND: Coronary heart disease is now the leading cause of death. Diagnosing myocardial infraction (MI) needs cardiac marker in case of equivocal clinical presentations and EKG interpretations. Troponin yields high sensitivity and specificity and could be used as a single screening assay. However, in actual practice, clinicians send CK-MB activity (CKMBa) as a combined marker with an expectation of providing additional diagnostic value due to large historical data. Discordant results from both markers lead to unclear management. Our study was to determine whether CKMBa has potential benefit for initial screening of MI in addition to cardiac troponin T (cTpT) in the Emergency Department (ED), and can this marker be safely removed from the routine laboratory panel in the emergency setting in Thailand. MATERIAL AND METHOD: We conducted a retrospective cohort single-center study to examine the usefulness of CKMBa in the ED from 907 patients who presented with clinically suspected acute M, and investigated with both biomarkers (CKMBa and cTpT). In these patients, 97 patients were included in the final analysis as they had negative cTpT associated with positive CKMBa or CKMBa turned to be positive within 24 hours after serial biomarkers measurements. The outcome was assessed by the final diagnosis, the cause of death if patients died during admission, and the 180-day mortality from medical chart review. In patients highly suspectedfor MI, further investigations were done including echocardiogram, exercise stress test, and coronay angiogram by experienced cardiologists. RESULTS: During the studyperiod, cTpTwere sent 1,772 times and most (95.2%) ofthe samples were associated with CKMBa results. The outcome showed that no one with negative cTpT was diagnosed as MI on a discharge diagnosis. Fourteen patients died during admission. The definitive cause was not defined as MI. The 180-day mortality was zero. During the follow-up, there was no MI suspected issues that needed further cardiac evaluations. The positive predictive value of CKMBa with negative cTpT was 0% (95% CI, 0-0.047). CONCLUSION: CKMBa added no benefit to cTpT in diagnosing acute MI in ED. Removing CKMBa from emergency panel could be considered.

Effect of the 2010 task force criteria on reclassification of cardiovascular magnetic resonance criteria for arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: We sought to evaluate the effect of application of the revised 2010 Task Force Criteria (TFC) on the prevalence of major and minor Cardiovascular Magnetic Resonance (CMR) criteria for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) versus application of the original 1994 TFC. We also assessed the utility of MRI to identify alternative diagnoses for patients referred for ARVC evaluation. METHODS: 968 consecutive patients referred to our institution for CMR with clinical suspicion of ARVC from 1995 to 2010, were evaluated for the presence of major and minor CMR criteria per the 1994 and 2010 ARVC TFC. CMR criteria included right ventricle (RV) dilatation, reduced RV ejection fraction, RV aneurysm, or regional RV wall motion abnormalities. When quantitative measures of RV size and function were not available, and in whom abnormal size or function was reported, a repeat quantitative analysis by 2 qualified CMR physicians in consensus. RESULTS: Of 968 patients, 220 (22.7%) fulfilled either a major or a minor 1994 TFC, and 25 (2.6%) fulfilled any of the 2010 TFC criterion. Among patients meeting any 1994 criteria, only 25 (11.4%) met at least one 2010 criterion. All patients who fulfilled a 2010 criteria also satisfied at least one 1994 criterion. Per the 2010 TFC, 21 (2.2%) patients met major criteria and 4 (0.4%) patients fulfilled at least one minor criterion. Eight patients meeting 1994 minor criteria were reclassified as satisfying 2010 major criteria, while 4 patients fulfilling 1994 major criteria were reclassified to only minor or no criteria under the 2010 TFC.Eighty-nine (9.2%) patients had alternative cardiac diagnoses, including 43 (4.4%) with clinically significant potential ARVC mimics. These included cardiac sarcoidosis, RV volume overload conditions, and other cardiomyopathies. CONCLUSIONS: Application of the 2010 TFC resulted in reduction of total patients meeting any diagnostic CMR criteria for ARVC from 22.7% to 2.6% versus the 1994 TFC. CMR identified alternative cardiac diagnoses in 9.2% of patients, and 4.4% of the diagnoses were potential mimics of ARVC.

Reference values of myocardial native T1 and extracellular volume in patients without structural heart disease and had negative 3T cardiac magnetic resonance adenosine stress test.

Background: To establish the reference values of native T1 and extracellular volume (ECV) in patients without structural heart disease and had a negative adenosine stress 3T cardiac magnetic resonance. Methods: Short-axis T1 mapping images were acquired using a modified Look-Locker inversion recovery technique before and after administration of 0.15 mmol/kg gadobutrol to calculate both native T1 and ECV. To compare the agreement between measurement strategies, regions of interest (ROI) were drawn in all 16 segments then averaged to represent mean global native T1. Additionally, an ROI was drawn in the mid-ventricular septum on the same image to represent the mid-ventricular septal native T1. Results: Fifty-one patients (mean 65 years, 65 % women) were included. Mean global native T1 averaged from all 16 segments and a mid-ventricular septal native T1 were not significantly different (1221.2 ± 35.2 vs 1228.4 ± 43.7 ms, p = 0.21). Men had lower mean global native T1 (1195 ± 29.8 vs 1235.5 ± 29.4 ms, p < 0.001) than women. Both mean global and mid-ventricular septal native T1 were not correlated with age (r = 0.21, p = 0.13 and r = 0.18, p = 0.19, respectively). The calculated ECV was 26.6 ± 2.7 %, which was not influenced by either gender or age. Conclusions: We report the first study to validate the native T1 and ECV reference ranges, factors influencing T1, and the validation across measurement methods in older Asian patients without structural heart disease and had a negative adenosine stress test. These references allow for better detection of abnormal myocardial tissue characteristics in clinical practice.

Prevalence of achlorhydria in an Asian population detected using Congo red staining during routine gastroscopy: 22 years' experience from a single centre.

OBJECTIVE: We aimed to study the prevalence of achlorhydria (AC) in a large Asian population. DESIGN: Medical records of patients who underwent oesophagogastroduodenoscopy (OGD) with Congo red staining method at the Vichaiyut Hospital from January 2010 to December 2019 were retrospectively reviewed. RESULTS: A total of 3597 patients was recruited; 223 were excluded due to concurrent use of proton pump inhibitors. Eighteen from 3374 patients (0.53%) had AC. Seven patients were presented with permanent AC (5F, 2M) (median age=69 years; range 58-92). Among 11 patients with temporary AC (5M, 6F: mean age 73.4 years; SD 13.2 years), all had gastrointestinal Helicobacter pylori bacterial infection and were over 45 years old. After successful treatment for H. pylori, AC was absent among patients with temporary AC. If counting only patients over 45 years of age, the prevalence of AC was 0.68% (18/2614). No adverse events arising from Congo red occurred. CONCLUSION: AC is relatively rare. Permanent and temporary AC were found only when they were over 55 and 45 years old, respectively. Staining Congo red on gastric mucosa can be safely and routinely incorporated into the OGD procedure for early detection of AC. We recommended a low-cost screening test such as serum vitamin B levels for screening only in patients aged 50 and over.

Association of Drug-Metabolizing Enzyme and Transporter Gene Polymorphisms and Lipid-Lowering Response to Statins in Thai Patients with Dyslipidemia.

PURPOSE: Statins are increasingly widely used in the primary and secondary prevention of cardiovascular disease. However, there is an inter-individual variation in statin response among patients. The study aims to determine the association between genetic variations in drug-metabolizing enzyme and transporter (DMET) genes and lipid-lowering response to a statin in Thai patients with hyperlipidemia. PATIENTS AND METHODS: Seventy-nine patients who received statin at steady-state concentrations were recruited. Serum lipid profile was measured at baseline and repeated after 4-month on a statin regimen. The genotype profile of 1936 DMET markers was obtained using Affymetrix DMET Plus genotyping microarrays. RESULTS: In this DMET microarray platform, five variants; SLCO1B3 (rs4149117, rs7311358, and rs2053098), QPRT (rs13331798), and SLC10A2 (rs188096) showed a suggestive association with LDL-cholesterol-lowering response. HDL-cholesterol-lowering responses were found to be related to CYP7A1 gene variant (rs12542233). Seven variants, SLCO1B3 (rs4149117, rs7311358, and rs2053098); SULT1E1 (rs3736599 and rs3822172); and ABCB11 (rs4148768 and rs3770603), were associated with the total cholesterol-lowering response. One variant of the ABCB4 gene (rs2109505) was significantly associated with triglyceride-lowering response. CONCLUSION: This pharmacogenomic study identifies new genetic variants of DMET genes that are associated with the lipid-lowering response to statins. Genetic polymorphisms in DMET genes may impact the pharmacokinetics and lipid-lowering response to statin. The validation studies confirmations are needed in future pharmacogenomic studies.

Prediction of nonviable myocardium by ECG Q-Wave parameters: A 3.0 T cardiovascular magnetic resonance study.

INTRODUCTION: The presence of a Q-wave on a 12-lead electrocardiogram (ECG) has been considered a marker of a large myocardial infarction (MI). However, the correlation between the presence of Q-waves and nonviable myocardium is still controversial. The aims of this study were to 1) test QWA, a novel ECG approach, to predict transmural extent and scar volume using a 3.0 Tesla scanner, and 2) assess the accuracy of QWA and transmural extent. METHODS: Consecutive patients with a history of coronary artery disease who came for myocardial viability assessment by CMR were retrospectively enrolled. Q-wave measurements parameters including duration and maximal amplitude were performed from each surface lead. A 3.0 Tesla CMR was performed to assess LGE and viability. RESULTS: Total of 248 patients were enrolled in the study (with presence (n = 76) and absence of pathologic Q-wave (n = 172)). Overall prevalence of pathologic Q-waves was 27.2% (for LAD infarction patients), 20.0 % (for LCX infarction patients), and 16.8% (for RCA infarction patients). Q-wave area demonstrated high performance for predicting the presence of a nonviable segment in LAD territory (AUC 0.85, 0.77-0.92) and a lower, but still significant performance in LCX (0.63, 0.51-0.74) and RCA territory (0.66, 0.55-0.77). Q-wave area greater than 6 ms mV demonstrated high performance in predicting the presence of myocardium scar larger than 10% (AUC 0.82, 0.76-0.89). CONCLUSION: Q-wave area, a novel Q-wave parameter, can predict non-viable myocardial territories and the presence of a significant myocardial scar extension.

Hypertension Subtypes among Thai Hypertensives: An Analysis of Telehealth-Assisted Instrument in Home Blood Pressure Monitoring Nationwide Pilot Project.

BACKGROUND: White-coat hypertension (HT), masked HT, HT with white-coat effect, and masked uncontrolled HT are well-recognized problems of over- and undertreatment of high blood pressure in real-life practice. However, little is known about the true prevalence in Thailand. OBJECTIVES: To examine the prevalence and characteristics of each HT subtype defined by mean home blood pressure (HBP) and clinic blood pressure (CBP) using telemonitoring technology in Thai hypertensives. METHODS: A multicenter, observational study included adult hypertensives who had been diagnosed for at least 3 months based on CBP without the adoption of HBP monitoring. All patients were instructed to manually measure their HBP twice a day for the duration of at least one week using the same validated automated, oscillometric telemonitoring devices (Uright model TD-3128, TaiDoc Corporation, Taiwan). The HBP, CBP, and baseline demographic data were recorded on the web-based system. HT subtypes were classified according to the treatment status, CBP (≥or <140/90 mmHg), and mean HBP (≥or <135/85 mmHg) into the following eight subtypes: in nonmedicated hypertensives, there are four subtypes that are normotension, white-coat HT, masked HT, and sustained HT; in treated hypertensives, there are four subtypes that are well-controlled HT, HT with white-coat effect, masked uncontrolled HT, and sustained HT. RESULTS: Of the 1,184 patients (mean age 58 ± 12.7 years, 59% women) from 46 hospitals, 1,040 (87.8%) were taking antihypertensive agents. The majority of them were enrolled from primary care hospitals (81%). In the nonmedicated group, the prevalence of white-coat and masked HT was 25.7% and 7.0%, respectively. Among the treated patients, the HT with white-coat effect was found in 23.3% while 46.7% had uncontrolled HBP (a combination of the masked uncontrolled HT (9.6%) and sustained HT (37.1%)). In the medicated older subgroup (n = 487), uncontrolled HBP was more prevalent in male than in female (53.6% vs. 42.4%, p=0.013). CONCLUSIONS: This is the first nationwide study in Thailand to examine the prevalence of HT subtypes. Almost one-fourth had white-coat HT or HT with white-coat effect. Approximately half of the treated patients especially in the older males had uncontrolled HBP requiring more intensive interventions. These results emphasize the role of HBP monitoring for appropriate HT diagnosis and management. The cost-effectiveness of utilizing THAI HBPM in routine practice needs to be examined in the future study.

Recurrent Takotsubo syndrome in a boy with Duchenne muscular dystrophy: A case report.

Takotsubo syndrome is a rare cause of reversible ventricular dysfunction that imitate an acute coronary syndrome. The entity is unusual among pediatric populations and a recurrent episode is extremely rare. We report a case of recurrent takotsubo syndrome in an eight-year-old boy with Duchenne muscular dystrophy (DMD). His chest pain episodes were aggravated by a strong emotional stimuli. During episodes of chest pain, electrocardiograms (ECG) showed ST elevation while echocardiograms showed left ventricle apical ballooning; however, a coronary angiography was normal. Serial ECG and echocardiogram revealed a spontaneous resolution of ST elevation and normalized apical contraction which were compatible with the diagnosis of takotsubo syndrome. Interestingly, serial cardiac magnetic resonance imaging demonstrated increasing subepicardial enhancement which was compatible with progression of cardiac involvement in DMD. .

Very late presentation of anomalous origin of the left coronary artery from the pulmonary artery: case report.

BACKGROUND: Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary anomaly. The enlarged right coronary artery provides retrograde collaterals to supply the left ventricle then preferentially directs into the lower pressure pulmonary artery system causing coronary steal phenomenon. Few patients who survive through adulthood without surgery must have abundant, well-formed functioning collaterals with adequate perfusion of the left ventricle. We present the oldest reported patient with ALCAPA to undergo corrective surgery. CASE PRESENTATION: A 79-year-old woman presented with a 3-months history of worsening shortness of breath and orthopnea. Physical examination discovered a soft continuous murmur at the left upper chest. Transthoracic echocardiography demonstrated an unusual, tubular-like structure inside the interventricular septum with a turbulent flow from color Doppler. Moreover, there was a severe mitral regurgitation from posterior mitral leaflet restriction associated with ventricular remodeling in combination with mitral annular dilatation. Coronary angiography and coronary computed tomography angiography established the diagnostic hallmark of ALCAPA syndrome. Stress cardiovascular magnetic resonance perfusion imaging demonstrated no myocardial ischemia suggesting adequate collateral circulation. Remarkably, there was a left coronary ostial stenosis, which served as a protective mechanism against myocardia ischemia by limiting the steal effect. The patient successfully underwent the ligation of anomalous artery at its origin in combination with bioprosthetic mitral valve replacement. Her postoperative course was uneventful. CONCLUSIONS: This case utilized multimodality imaging for delineating the course of abnormal vessels and helping to formulate therapeutic decision.

Defining left ventricular noncompaction using cardiac computed tomography.

PURPOSE: Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by a distinctive 2-layered appearance of the myocardium because of increased trabeculation and deep intertrabecular recesses. Echocardiography serves as the initial noninvasive diagnostic test. Currently, magnetic resonance imaging (MRI) is increasingly being used to diagnose LVNC because of its improved temporal and spatial resolution. So far, no criteria have been proposed to define pathologic LVNC with the use of computed tomography (CT). MATERIALS AND METHODS: We analyzed CT images using an American Heart Association 17-segment model in 8 patients previously diagnosed with LVNC by clinical diagnosis, echocardiography, and/or MRI, as well as in 11 patients with nonischemic dilated cardiomyopathy, 11 patients with hypertrophic cardiomyopathy, 10 patients with severe aortic stenosis, 9 patients with severe aortic regurgitation, 10 patients with left ventricular hypertrophy due to essential hypertension, and, additionally, in a control group of 20 patients who had normal CT scans without a history of cardiovascular disease. The distribution of LVNC was assessed by qualitative analysis of 17 myocardial segments for the presence or absence of any degree of noncompaction. Each segment was analyzed in each of the 3 end-diastolic long-axis views for the presence or absence of noncompaction, and the most prominent trabeculation was chosen for measurement. The left ventricular apex was excluded. Thickness of noncompacted and compacted myocardium was measured perpendicular to the compacted myocardium. The ratio of noncompacted to compacted (NC:C) myocardium was calculated for each segment. Receiver operating characteristics were used to generate cutoff values with sensitivity and specificity to distinguish the LVNC group from other groups. RESULTS: An end-diastolic NC:C ratio >2.3 distinguished pathologic LVNC with 88% sensitivity and 97% specificity; positive and negative predictive values were 78% and 99%, respectively. CONCLUSIONS: CT using the standard MRI NC:C ratio cutoff >2.3 accurately characterizes pathologic LVNC.

Serum NT-proBNP in the early detection of doxorubicin-induced cardiac dysfunction.

AIM: Cardiac dysfunction is a major limitation of anthracycline treatment in cancer patients. There are several useful serum markers in other types of cardiomyopathy, including N-terminal pro-brain-natriuretic peptide (NT-proBNP), troponin-T and creatine kinase MB isoform. We investigated the potential application of these serum biomarkers in cancer patients receiving treatment with anthracycline. METHODS: We collected data from 52 female breast cancer patients receiving doxorubicin and cyclophosphamide every 3 weeks for four cycles. Cardiac function evaluations by echocardiography were done at baseline and at the end of the fourth cycle of chemotherapy. Patients' blood samples were serially measured for cardiac biomarkers. RESULTS: The mean cumulative dose of doxorubicin in this study was 237 mg/m(2) . No symptomatic heart failure was detected during the study period. However, there were significant asymptomatic reductions of left ventricular ejection fraction (LVEF) from mean ± SD 70.7 ± 6% at baseline to 67.0 ± 5% (P < 0.001). By clinical toxicity criteria the LVEF decline was grade I in 18% and grade II in 4%. After one dose of chemotherapy, a significant rise of serum NT-proBNP occurred in patients who subsequently developed an LVEF reduction compared with patients with normal LVEF (P = 0.04). A correlation analysis demonstrated that the reduction of fractional shortening was significantly associated with elevated NT-proBNP (r = -0.016, P = 0.014). CONCLUSION: Asymptomatic reductions in cardiac function are common in breast cancer patients treated with doxorubicin. NT-proBNP may serve as a convenient serum biomarker for the early detection of cardiotoxicity induced by anthracycline.

Clinical experiences of delayed contrast enhancement with cardiac computed tomography: case series.

BACKGROUND: Myocardial delayed enhancement (MDE) by gadolinium-enhanced cardiac MRI is well established for myocardial scar assessment in ischemic and non-ischemic heart disease. The role of MDE by cardiac CT (CT-MDE) is not yet defined. FINDINGS: We reviewed all clinical cases of CT-MDE at a tertiary referral center to present the cases as a case series. All clinical cardiac CT exams which utilized CT-MDE imaging between January 1, 2005 and October 1, 2010 were collected as a series and their findings were also compared with available myocardial imaging to assess for myocardial abnormalities, including echocardiography (wall motion, morphology), cardiac MRI (delayed enhancement, morphology), SPECT MPI (perfusion defects). 5,860 clinical cardiac CT exams were performed during the study period. CT-MDE was obtained in 18 patients and was reported to be present in 9 patients. The indications for CT-MDE included ischemic and non-ischemic heart diseases. In segments positive for CT-MDE, there was excellent agreement of CT with other modalities: echocardiography (n=8) demonstrated abnormal morphology and wall motion (k=1.0 and k=0.82 respectively); prior MRI (n=2) demonstrated abnormal delayed enhancement (MR-MDE) (k=1.0); SPECT MPI (n=1) demonstrated fixed perfusion defects (k=1.0). In the subset of patients without CT-MDE, no abnormal segments were identified by echocardiography (n=8), MRI (n=1) and nuclear MPI (n=0). CONCLUSIONS: CT-MDE was performed in rare clinical situations. The indications included both ischemic and non-ischemic heart disease and there was an excellent agreement between CT-MDE and abnormal myocardium by echocardiography, cardiac MRI, and nuclear MPI.

Comparison of dual-source 64-slice adenosine stress CT perfusion with stress-gated SPECT-MPI for evaluation of left ventricular function and volumes.

BACKGROUND: Evaluation of left ventricular (LV) volumes and ejection fraction (LVEF) represent important components of pharmacologic stress imaging with either myocardial CT perfusion (CTP) or gated single-photon emission CT (SPECT) myocardial perfusion imaging (SPECT-MPI). OBJECTIVES: We compared measurements of left ventricular function and volumes obtained with CTP and SPECT-MPI. METHODS: Forty-seven patients (mean age, 62 ± 11 years; male, n = 39) underwent stress CTP and SPECT-MPI. LVEF (in %), end-systolic volume (ESV; in mL), and end-diastolic volume (EDV; in mL) derived from stress CTP images were compared with SPECT-MPI. RESULTS: Stress CTP was in good agreement with SPECT-MPI for quantification of LVEF (r = 0.91), EDV (r = 0.75), and ESV (r = 0.83; all P < 0.001). The mean LVEF measured by stress CTP (66% ± 17%) was similar to SPECT-MPI (64% ± 15%). Similar values were also derived for mean EDV (123 ± 30 mL vs 120 ± 34 mL) and ESV (44 ± 28 mL vs 51 ± 34 mL) for CTP and SPECT-MPI, respectively. Good agreement was also shown between both techniques for the assessment of regional wall motion with identical wall motion scores in 95.3% of the segments (κ = 0.79). CONCLUSIONS: LVEF and LV volume parameters as determined by dual-source 64-slice adenosine stress CTP show a high correlation with values obtained with stress-gated SPECT-MPI.