Identification of a novel LDLR p.Glu179Met variant in Thai families with familial hypercholesterolemia and response to treatment with PCSK9 inhibitor.

Familial hypercholesterolemia (FH) is a genetic disease characterized by elevated LDL-C levels. In this study, two FH probands and 9 family members from two families from northeastern Thailand were tested for LDLR, APOB, and PCSK9 variants by whole-exome sequencing, PCR-HRM, and Sanger sequencing. In silico analysis of LDLR was performed to analyse its structure‒function relationship. A novel variant of LDLR (c.535_536delinsAT, p.Glu179Met) was detected in proband 1 and proband 2 in homozygous and heterozygous forms, respectively. A total of 6 of 9 family members were heterozygous for LDLR p.Glu179Met variant. Compared with proband 2, proband 1 had higher baseline TC and LDL-C levels and a poorer response to lipid-lowering therapy combined with a PCSK9 inhibitor. Multiple sequence alignment showed that LDLR p.Glu179Met was located in a fully conserved region. Homology modelling demonstrated that LDLR p.Glu179Met variant lost one H-bond and a negative charge. In conclusion, a novel LDLR p.Glu179Met variant was identified for the first time in Thai FH patients. This was also the first report of homozygous FH patient in Thailand. Our findings may expand the knowledge of FH-causing variants in Thai population, which is beneficial for cascade screening, genetic counselling, and FH management to prevent coronary artery disease.

Prognostic Value of Ankle-Brachial Index in Prediction of Cardiovascular Events in an Asian Population with Multiple Atherosclerotic Risk Factors.

We aimed to evaluate the incremental prognostic value after incorporation of the ankle-brachial index (ABI) into the 10-year pool cohort equation (PCE) risk model in patients with multiple risk factors (MRFs). A total of 4332 MRFs patients were divided into 2 groups as ABI ≤.9 or >.9. The primary outcome was hard cardiovascular events (hCVE: including cardiovascular death, myocardial infarction, or ischemic stroke) over a median follow-up of 36 months. The Cox proportional hazards survival model, C-statistic, and net reclassification indices (NRI) were used. The occurrence of the primary outcome in the ABI ≤.9 group (3.7%) was significantly greater than in the ABI > .9 group (1.3%), P < .001. ABI is an independent predictor of hCVE in addition to the variables in the standard risk model (age, gender, and smoking status). ABI modestly improved the C-index when added to the PCE risk model (PCE .70 vs ABI+PCE .74). The addition of ABI to the PCE risk model did not significantly improve the classification of patients (NRI -.029; 95% CI: -.215 to .130). Despite ABI being one of the independent predictors of hCVE, integration of ABI into the PCE model did not improve the efficacy of risk reclassification in patients with MRFs.

Gut microbiota-generated metabolite, trimethylamine-N-oxide, and subclinical myocardial damage: a multicenter study from Thailand.

Plasma Trimethylamine-N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, is mechanistically linked to cardiovascular disease (CVD) and adverse cardiovascular events. We aimed to examine the relationship between plasma TMAO levels and subclinical myocardial damage using high-sensitivity cardiac troponin-T (hs-cTnT). We studied 134 patients for whom TMAO data were available from the Cohort Of patients at a high Risk of Cardiovascular Events-Thailand (CORE-Thailand) registry, including 123 (92%) patients with established atherosclerotic disease and 11 (8%) with multiple risk factors. Plasma TMAO was measured by NMR spectroscopy. In our study cohort (mean age 64 ± 8.9 years; 61% men), median TMAO was 3.81 µM (interquartile range [IQR] 2.89-5.50 µM), and median hs-cTnT was 15.65 ng/L (IQR 10.17-26.67). Older patients and those with diabetic or hypertension were more likely to have higher TMAO levels. Plasma TMAO levels correlated with those of hs-cTnT (r = 0.54; p < 0.0001) and were significantly higher in patients with subclinical myocardial damage (hs-cTnT ≥ 14 ng/L; 4.48 µM vs 2.98 µM p < 0.0001). After adjusting for traditional risk factors, elevated TMAO levels remained independently associated with subclinical myocardial damage (adjusted odds ratio [OR]: 1.58; 95% CI 1.24-2.08; p = 0.0007). This study demonstrated that plasma TMAO was an independent predictor for subclinical myocardial damage in this study population.

Age-Related Clinical Outcomes of Patients with Non-Valvular Atrial Fibrillation: Insights from the COOL-AF Registry.

PURPOSE: We aimed to compare the rate of clinical outcomes among three age groups (<65, 65-74, and ≥75 years) of adult patients with non-valvular atrial fibrillation (NVAF). PATIENTS AND METHODS: We prospectively enrolled NVAF patients from 27 Thailand medical centers. The following were collected at baseline: demographic data, risk factors, comorbid conditions, laboratory data, and medications. The clinical outcomes were ischemic stroke (IS) or transient ischemic attack (TIA), major bleeding (MB), intracerebral hemorrhage (ICH), heart failure (HF), and death. All events were adjudicated. Patients were categorized according to age group into three groups; age <65, 65-74, and ≥75 years. RESULTS: Among the 3402 patients that were enrolled during 2014-2017, the mean age was 67.4±11.3 years, and 2073 (60.9%) were older. The average follow-up was 25.7±10.6 months. Oral anticoagulants were given in 75.4% of patients (91.1% of OAC was warfarin). The incidence rate of IS/TIA, MB, ICH, HF, and death was 1.43 (1.17-1.74), 2.11 (1.79-2.48), 0.70 (0.52-0.92), 3.03 (2.64-3.46), and 3.77 (3.33-4.24) per 100 person-years, respectively. The risk of IS/TIA, MB, ICH, HF, and death increased with age both before and after adjustment for potential confounders. Even though OAC reduced the risk of IS/TIA, it increased the risk of MB. Net clinical benefit (NCB) analysis favored oral anticoagulant (OAC) in the high-risk subset of older adults. CONCLUSION: Older adult NVAF patients had a significantly increased risk of IS/TIA, MB, ICH, HF, and death compared to younger NVAF before and after adjustment for potential confounders. Strategies to reduce overall risk, including OAC use and choice and integrated care, should be implemented.

History of major bleeding predicts risk of clinical outcome of patients with atrial fibrillation: results from the COOL-AF registry.

OBJECTIVE: To compare clinical outcomes between patients with and without history of major bleeding according to types of antithrombotic medications in patients with non-valvular atrial fibrillation (NVAF). METHODS: We conducted a multicenter registry of patients with NVAF during 2014 to 2017 in Thailand. The following data were collected: demographic data, type of NVAF, medical illness, components of CHA2DS2-VASc and HAS-BLED scores, history of bleeding and severity, investigations, and antithrombotic medications. Clinical outcomes were death, bleeding, and ischemic stroke/transient ischemic attack (TIA). RESULTS: There were a total of 3218 patients. The average age was 67.3 ± 11.3 years, and 58.3% were men. Sixty-nine patients (2.14%) had a history of major bleeding. Antithrombotic use was, as follows: 2126 patients (75.3%) received oral anticoagulant (OAC) alone, 555 (17.2%) received antiplatelet alone, 298 (9.3%) received both, and 239 (7.4%) received neither. During follow-up, 9.9% had major adverse outcomes, including death (5.9%), ischemic stroke/TIA (2.5%), and major bleeding (4.0%). There were no significant differences in the types of antithrombotic medications between patients with and without history of major bleeding. Multivariate analysis revealed old age, low body mass index, hypertension, diabetes, heart failure, and history of major bleeding to be independently associated with major adverse outcome. Adverse events significantly increased in patients with OAC plus antiplatelet. CONCLUSIONS: History of major bleeding was identified as a factor that significantly affects clinical outcome. Inappropriate use of OAC plus antiplatelet should be avoided. Special caution should be made in this high-risk patients.

Risk profiles and pattern of antithrombotic use in patients with non-valvular atrial fibrillation in Thailand: a multicenter study.

BACKGROUND: Anticoagulation therapy is a standard treatment for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) that have risk factors for stroke. However, anticoagulant increases the risk of bleeding, especially in Asians. We aimed to investigate the risk profiles and pattern of antithrombotic use in patients with NVAF in Thailand, and to study the reasons for not using warfarin in this patient population. METHODS: A nationwide multicenter registry of patients with NVAF was created that included data from 24 hospitals located across Thailand. Demographic data, atrial fibrillation-related data, comorbid conditions, use of antithrombotic drugs, and reasons for not using warfarin were collected. Data were recorded in a case record form and then transferred into a web-based system. RESULTS: A total of 3218 patients were included. Average age was 67.3 ± 11.3 years, and 58.2% were male. Average CHADS2, CHA2DS2-VASc, and HAS-BLED score was 1.8 ± 1.3, 3.0 ± 1.7, and 1.5 ± 1.0, respectively. Antiplatelet was used in 26.5% of patients, whereas anticoagulant was used in 75.3%. The main reasons for not using warfarin in those with CHA2DS2-VASc ≥2 included already taking antiplatelet (26.6%), patient preference (23.1%), and using non-vitamin K antagonist oral anticoagulants (NOACs) (22.7%). Anticoagulant was used in 32.3% of CHA2DS2-VASc 0, 56.8% of CHA2DS2-VASc 1, and 81.6% of CHA2DS2-VASc ≥2. The use of NOACs increased from 1.9% in 2014 to 25.6% in 2017. CONCLUSIONS: Anticoagulation therapy was prescribed in 75.3% of patients with NVAF. Among those receiving anticoagulant, 90.9% used warfarin and 9.1% used NOACs. The use of NOACs increased over time.

Relationship between Peripheral Arterial Stiffness and Estimated Pulmonary Pressure by Echocardiography in Systemic Sclerosis.

BACKGROUND: Pulmonary hypertension (PH) is an important lethal manifestation of systemic sclerosis (SSc). Evidence of an association between peripheral and pulmonary arterial vasculopathy in SSc has been demonstrated. We hypothesized that peripheral arterial stiffness could predict PH in SSc. METHODS: We performed a cross-sectional study among patients with SSc who underwent Cardio-Ankle Vascular Index (CAVI, VaSera VS-1000; Fukuda Denshi, Tokyo, Japan) and transthoracic echocardiography (TTE) examination to evaluate peripheral arterial stiffness and PH, respectively. The correlation between CAVI score and PH hemodynamics [right ventricular systolic pressure (RVSP) and tricuspid regurgitation velocity (TRV)] was studied. RESULTS: A total of 145 patients underwent both CAVI and TTE evaluation. The mean (standard deviation, SD) patient age was 51.5 (12.3) years; female patients constituted 72% of the subjects. Diffuse SSc occurred in 75% of the cases. The mean (SD) CAVI score was 7.6 (0.9), and the mean (SD) RVSP was 29.9 (11.2) mmHg. Correlation coefficient (r) between CAVI score and RVSP in overall, limited, and diffuse SSc were 0.107 (p = 0.200), 0.040 (p = 0.815), and 0.194 (p = 0.043), respectively. CAVI scores were borderline or abnormal (≥ 8) in 30.3% of subjects. PH was classified intermediate or high probability (TRVmax ≥ 2.9 m/s) in 19.3% of the subjects. Among the overall population, the odds ratios (95% CI) of CAVI score ≥ 8 for TRVmax ≥ 2.9 m/s in univariate and multivariate analysis were 1.23 (0.46-3.21, p = 0.678), and 0.54 (0.10-2.84, p = 0.471), respectively. CONCLUSIONS: Peripheral arterial stiffness, as measured by CAVI, has a correlation trend with the level of pulmonary arterial pressure assessed by TTE, specifically in the diffuse SSc subgroup.

The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients.

PURPOSE: The aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients. METHODS: A total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.g., age, body mass index, indications for warfarin and concomitant medications, were documented. Four single nucleotide polymorphisms in the VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622, and UGT1A1 rs887829 genes were detected from gDNA using TaqMan allelic discrimination assays. RESULTS: The patients with variant genotypes of VKORC1 - 1639G > A required significantly lower warfarin stable weekly doses (SWDs) than those with wild-type genotype (p < 0.001). Similarly, the patients with CYP2C9*3 variant allele required significantly lower warfarin SWDs than those with homozygous wild-type (p = 0.006). In contrast, there were no significant differences in the SWDs between the patients who carried variant alleles of CYP4F2 rs2108622 and UGT1A1 rs887829 as compared to wild-type allele carriers. Multivariate analysis, however, showed that CYP4F2 rs2108622 TT genotype accounted for a modest part of warfarin dose variability (1.2%). In contrast, VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622 genotypes and non-genetic factors accounted for 51.3% of dose variability. CONCLUSIONS: VKORC1 - 1639G > A, CYP2C9*3, and CYP4F2 rs2108622 polymorphisms together with age, body mass index, antiplatelet drug use, amiodarone use, and current smoker status explained 51.3% of individual variability in stable warfarin doses. In contrast, the UGT1A1 rs887829 polymorphism did not contribute to dose variability.

Kussmaul's sign and rapid X-Y descents in constrictive pericarditis.

Right-sided heart failure is not uncommon. A careful jugular venous examination looking for the distinct Kussmaul's sign and rapid X-Y descents, which are highly indicative of constrictive pericarditis, is markedly helpful in guiding the correct diagnosis and proper management.

Management and risk factor control of coronary artery disease in elderly versus nonelderly: a multicenter registry.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of death in elderly because aging is the important non-modifiable risk factors of atherosclerosis and also a predictor of poor outcomes. Underuse of guideline directed therapy may contribute to suboptimal risk factor control and worse outcomes in the elderly. We aimed to explore the management of CAD, risk factors control as well as goal attainment in elderly compared to nonelderly CAD patients. METHODS: The CORE-Thailand is an ongoing multicenter, prospective, observational registry of patients with high atherosclerotic risk in Thailand. The data of 4120 CAD patients enrolled in this cohort was analyzed comparing between the elderly (age ≥ 65 years) vs. nonelderly (age < 65 years). RESULTS: There were 2172 elderly and 1948 nonelderly patients. The elderly CAD patients had higher prevalence of hypertension, dyslipidemia, atrial fibrillation and chronic kidney disease. The proportion of patients who received coronary revascularization was not different between the elderly and nonelderly CAD patients. Antiplatelets were prescribed less in the elderly while statin was prescribed in the similar proportion. Goal attainments of risk factor control of glycemic control, low density lipoprotein cholesterol, and smoking cessation except the blood pressure goal were higher in the elderly CAD patients. CONCLUSIONS: The CORE-Thailand registry showed the equity in the treatment of CAD between elderly and non-elderly. Elderly CAD patients had higher rate of goal attainment in risk factor control except blood pressure goal. The effects of goal attainment on cardiovascular outcomes will be demonstrated from ongoing cohort.

Left atrial coagulation activity in patient with mitral stenosis in sinus rhythm.

OBJECTIVE: Anticoagulation therapy is strongly recommended in all patients with mitral stenosis (MS) in atrial fibrillation (AF) but this treatment is controversial in patients in sinus rhythm (SR). The objective of the present study was to investigate the coagulation activity in patients with MS in sinus rhythm compared to those in atrial fibrillation. MATERIAL AND METHOD: The authors studied the levels of biochemical markers of thrombin generation (thrombin-anti-thrombin [TAT] complex,fibrinogen, and factor XIII) and fibrinolysis (D-dimer) in specimens of blood from the atria in 35 consecutive patients with moderate to severe MS (18 in sinus rhythm and 17 in AF) who underwent percutaneous balloon mitral valvotomy. RESULTS: The levels coagulation factors in left atrium in patients with MS in SR and AF were thrombin-anti-thrombin complex = 77.21 +/- 8.87 mg/L vs. 73.48 +/- 7.78 mg/L, p = 0.755, fibrinogen = 356.57 +/- 41.86 mg/L vs. 271.62 +/- 22.47 mg/L, p = 0.089, factor XIII = 139.88 +/- 8.96 mg/L vs. 123.42 +/- 6.24 mg/L, p = 0.152, and D-dimer = 846.14 +/- 137.84 mg/L vs. 693.88 +/- 164.67 mg/L, p = 0.481. Levels of coagulation activities did not correlate with the left atrial size. CONCLUSION: This present study demonstrates that coagulation activity is not different whether they are in SR or in AF and suggests that anticoagulation therapy should be considered in these patients.

Right ventricular systolic pressure assessed by echocardiography: a predictive factor of mortality in patients with scleroderma.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a well-known complication of systemic sclerosis (SSc). Doppler echocardiographic screening for the detection of PAH (by measuring right ventricular systolic pressure [RVSP]) is therefore recommended for all patients with SSc. However, the validity of RVSP as a predictor of mortality in patients with SSc is not well established. HYPOTHESIS: Doppler-determined PAH identifies a high-risk subset of patients with SSc with decreased survival. METHODS: We performed echocardiography in 155 consecutive patients with SSc between May 2005 and July 2006 and tested the value of an RVSP level of ≥36 mm Hg to predict mortality. Cox proportional hazards model was used to examine the individual relationship between each variable and the mortality rate. RESULTS: Tricuspid regurgitant jets for RVSP determination were quantified in 129 patients (82.6%), of which 47 (36.4%) had RVSP ≥36 mm Hg. The median follow-up time was 34 months. The 1-, 2-, and 3-year survival rates were significantly lower among SSc patients with RVSP ≥36 vs ≤36 mm Hg (82%, 78%, and 67% vs 98%, 90%, and 86%, respectively, P < 0.01 by Wilcoxon test). In a multivariate analysis including echocardiographic and clinical variables, only an RVSP ≥36 mm Hg and a New York Heart Association III/IV class were associated with increased mortality; the respective Cox hazard ratios were 2.22 (95% confidence interval [CI]: 1.01-4.89, P = 0.048) and 4.77 (95% CI: 2.09-10.90, P = 0.000). CONCLUSIONS: Our results indicate that Doppler RVSP identifies a high-risk subset and supports the use of Doppler RVSP as a screening test in patients with SSc who may warrant early treatment of their PAH.

Drug-eluting stent for unprotected left main coronary artery disease: early and mid-term outcomes.

BACKGROUND: PCI is increasingly performed in patients with ULMCA disease. The efficacy and safety of drug-eluting stents in ULMCA disease have been reported. OBJECTIVE: To evaluate the early and mid-term clinical outcome of the Percutaneous Coronary Intervention (PCI) with Drug-Eluting stent (DES) in unprotected left main coronary artery (ULMCA) disease patients. MATERIAL AND METHOD: PCI with DES was performed with 90 consecutive patients having ULMCA disease between January 2006 and June 2009. RESULTS: At a median follow-up of 22.8 +/- 12.2 months, major adverse cardiac or cerebrovascular events (MACCE) occurred in 11 (12.2%) patients. There were seven (7.8%) deaths including two (2.2%) cardiac deaths and five (5.6%) non-cardiac deaths. There was one MI (1.1%), and four (4.4%) target vessel revascularization. Restenosis in the left main occurred only in two patients (2.2%) and definite stent thrombosis occurred in two patients (2.2%). CONCLUSION: The present study demonstrates that PCI with Drug-Eluting stent implantation in unprotected left main coronary artery disease is a safe form of treatment and has favorable outcomes.

Predictive factors of systemic embolism in patients with mitral stenosis in sinus rhythm.

BACKGROUND: Systemic embolism is one of the major complications in patients with mitral stenosis (MS) who are in atrial fibrillation; however, this serious complication can also occur in patients with MS in sinus rhythm. OBJECTIVE: The purpose of the present study was to identify the predictive factors of systemic emboli in patients with MS in sinus rhythm. MATERIAL AND METHOD: Twenty patients with MS in sinus rhythm with recent cerebral embolism and 32 with MS in sinus rhythm without any history of systemic embolism were studied between January 2004 and May 2006. Clinical and echocardiographic data were assessed using stepwise logistic regression for prediction of systemic embolism. RESULTS: Age (odds ratio [OR], 1.14; 95% confidence interval [CI] 1.04-1.26) and left atrial spontaneous echo contrast (LASEC) grade 3+ and 4+ (OR, 46.42; 95% CI, 5.00-436.49) were associated with, and predictive of systemic emboli, whereas left atrial appendage contraction flow velocities, left atrial size and mitral valve area were not. CONCLUSION: The present study demonstrates that age and LASEC are the major predictive factors of systemic embolism in patients with MS in sinus rhythm. It would therefore be prudent to give anticoagulants to patients in atrial fibrillation as well as to those in sinus rhythm at risk of systemic embolism.

Cardiac troponin-T in pre-end stage kidney disease.

BACKGROUND: Cardiac troponin T level (cTnT) is commonly increased in end stage chronic kidney disease (CKD) in the absence of acute myocardial infarction. There are few data available on serum cTnT concentration in patients with pre-end stage CKD. OBJECTIVE: To evaluate the correlation of cTnT level and severity of kidney disease in patients with CKD stage 3 and 4 and to evaluate whether there is a relationship between left ventricular mass index and cTnT level. MATERIAL AND METHOD: Patients (103) with CKD stage 3-4 between 26 and 85 years of age (mean 60.0 +/- 11.9) entered the present study. Serum cTnT determined using a third-generation electrochemiluminescent immunoassay on an Elecsys 2010 analyzer (Roche Diagnostics Ltd.). All patients underwent echocardiography. Left ventricular hypertrophy (LVH) was considered when LV mass index exceeded 125 g/m2. RESULTS: Overall, 28 patients (28.2%) had cTnT > 0.01 micro/L and two patients (1.8%) had cTnT > 0.1 microg/L cTnT concentration was commonly increased in more severe CKD (9 patients in stage 3 and 20 patients in stage 4). LVH was not associated with increased cTnT (p=0.105). CONCLUSION: The present study demonstrated that the elevated cTnT > 0.01 microg/L is relatively common in patients with CKD stage 3-4 who do not require dialysis treatment, however serum cTnT level above > 0.1 microg/L is uncommon in this population. Increased serum cTnT is associated with decreased renal clearance but not LVH.

Predictors of in-hospital mortality in non-ST elevation acute coronary syndrome in Thai Acute Coronary Syndrome Registry (TACSR).

OBJECTIVE: To determine baseline prognostic factors of in-hospital mortality in Thai patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). MATERIAL AND METHOD: Among 5,537 NSTE-ACS patients enrolled in Thai Acute Coronary Syndrome Registry, a univariate analysis and multivariate analysis were used to estimate the relationship of baseline clinical variables and in-hospital mortality. Variables examined included demographics, history and presenting characteristics. RESULTS: The in-hospital mortality rate was 9.5%. The statistically significant, adjusted baseline prognostic factors of in-hospital death were older age > or =65 years) (odds ratio [OR] 2.2, 95% confidence interval [CI] = 1.54-3.09), shock at presentation (OR 4.6, 95%CI = 2.91-7.32), heart failure (OR 3.1, 95%CI = 2.15-4.38), positive cardiac marker (OR 1.7, 95%CI = 1.18-2.53), arrhythmia (OR 12.3, 95%CI = 8.71-17.35), major bleeding (OR 2.9, 95%CI = 1.84-4.51), and cerebrovascular accident (OR 4.9, 95% CI = 2.42-9.97). While dyslipidemia (OR 0.6, 95%CI = 0.45-0.87), having percutaneous coronary intervention (OR 0.6, 95% CI = 0.39-0.94), receiving aspirin (OR 0.6, 95%CI = 0.33-0.94), beta-blocker (OR 0.5, 95% CI = 0.40-0.73), angiotensin converting enzyme inhibitor (OR 0.6, 95% CI = 0.43-0.78) and nitrate (OR 0.5, 95%CI= 0.35-0.76) were associated with lower in-hospital mortality. CONCLUSION: The in-hospital mortality is higher in Thai NSTE-ACS patients compared to other populations. The present study supports and confirms the prognostics importance of several baseline characteristics reported in previous studies.

Resolution of left atrial thrombus after 6 months of anticoagulation in candidates for percutaneous transvenous mitral commissurotomy.

BACKGROUND: Resolution of left atrial thrombus after long-term oral anticoagulation enhances safe percutaneous transvenous mitral commissurotomy (PTMC); however, the short-term benefit has not been defined. OBJECTIVES: To estimate the resolution rate of left atrial thrombus among PTMC candidates after 6 months of oral anticoagulation and to determine its main predictors. DESIGN: Prospective cohort. SETTING: Community-based university medical center. PATIENTS: 219 PTMC candidates with thrombus demonstrated by multiplane transesophageal echocardiographic studies. MEASUREMENTS: The primary outcome was the status of the thrombus at the first 6-month follow-up; secondary measures were bleeding or thromboembolic complications. RESULTS: Among 219 PTMC candidates with left atrial thrombus (mean age [+/-SD], 39.6 +/- 7.4 years [range, 19 to 62 years]), complete resolution of thrombus, with an overall disappearance rate of 24.2% (95% CI, 18.5% to 29.9%), was demonstrated in 53 patients who subsequently underwent successful PTMC. In another 166 patients, the thrombus size was reduced by 24% (P < 0.001). No thrombus resolution was observed in the 27 patients with a left atrial body thrombus. Eighteen patients had minor bleeding. The significant predictors of thrombus resolution were a New York Heart Association class of 2 or less, a left atrial appendage thrombus size of 1.6 cm2 or less, a left atrial spontaneous echocardiographic contrast grade of 1 or less, and an international normalized ratio (INR) of at least 2.5. Patients with all of these predictors had a 94.4% chance of complete thrombus resolution (CI, 84.4% to 98.1%). CONCLUSIONS: After 6 months of oral anticoagulation, the left atrial thrombus disappeared in about a quarter of PTMC candidates so they could safely undergo PTMC. Less clinical severity, lower grading of the left atrial spontaneous echocardiographic contrast, a smaller thrombus, and a higher INR level predict thrombus resolution.

Resolution of left atrial thrombi with anticoagulant therapy in candidates for percutaneous transvenous mitral commissurotomy.

BACKGROUND AND AIMS OF THE STUDY: Little is known of the fate of left atrial thrombus (LAT) among candidates for percutaneous transvenous mitral commissurotomy (PTMC) after oral anticoagulation (OA) therapy. The aim of this study was to estimate the resolution rate of documented LAT, and to determine its significant predictors among this population. METHODS: In this prospective cohort study all consecutive candidates for PTMC with documented LAT were followed between August 1996 and December 1999. All patients underwent both transthoracic (TTE) and transesophageal echocardiography (TEE) and received OA therapy (INR 2.0-3.0). The fate of LAT was studied serially using both TTE and TEE. RESULTS: A total of 75 patients was followed for six to 34 months (mean 12.2+/-6.2 months; total 914 patient-months). The LAT was completely resolved in 48 patients (5.25 per 100 pt-months; 95% CI 3.96-6.97). The overall resolution rate was 63.0 per 100 patients per year (95% CI 47.5-83.6). Patients with resolved LAT underwent uneventful PTMC. The median duration of LAT resolution was 16 months (95% CI 12.7-19.3). Significant predictors of LAT resolution were the size of the LAT (RR = 0.8 for each 1 cm2 increase in LAT; 95% CI 0.6-0.9; p = 0.012) and severity of the left atrial spontaneous echo contrast (LASEC) detected by TEE (RR = 0.6 for each 1 level increase of the LASEC severity score; 95% CI 0.4-0.9; p = 0.032). CONCLUSION: The smaller the LAT and the less severe the LASEC, the greater the likelihood of LAT resolution after OA therapy and the enhanced possibility of safely performing PTMC.

A prognostic model for predicting the disappearance of left atrial thrombi among candidates for percutaneous transvenous mitral commissurotomy.

OBJECTIVES: We sought to develop a prognostic model to predict the disappearance of left atrial thrombi (LAT) among candidates for percutaneous transvenous mitral commissurotomy (PTMC). BACKGROUND: Complete LAT resolution can be achieved with oral anticoagulation, allowing a number of patients to safely undergo PTMC. METHODS: We randomly allocated 108 PTMC candidates with LAT into two subsets---one to derive the model and the other to validate it. The existence of LAT and its size were measured by transesophageal echocardiography. Patients were given oral anticoagulation and followed up for 6 to 34 months. There was a 62% disappearance rate of LAT. RESULTS: We developed the following model: P = 1/(1 + exponential [-8.1 + 1.8 NYHA + 0.7 area]), where NYHA = New York Heart Association functional class (from I to IV), and area = LAT area (in cm(2)). The model was well calibrated (goodness-of-fit test, p = 0.82) and well discriminated (area under the receiver-operating characteristics [ROC] curve = 0.92). Performance in the validating sample was equally good (area under the ROC curve = 0.94; goodness-of-fit test, p = 0.16). When a cut-off point of p > 0.7 was used to designate the LAT disappearance in the validating set, the model had a sensitivity, specificity and positive and negative predictive values of 93.3%, 79.2%, 84.9% and 90.5%, respectively. CONCLUSIONS: Combined clinical (NYHA functional class) and echocardiographic (LAT area) variables are predictive of the 34-month outcome of oral anticoagulation for LAT resolution among PTMC candidates. This simple and highly predictive model might be potentially useful for clinical assessment and proper management.