Hazard Ratios For Cardiac Events Research Articles

Assays of Variant Effect and Automated Patch Clamping Improve KCNH2-LQTS Variant Classification and Cardiac Event Risk Stratification.

Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by KCNH2. Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance. Here we sought to test whether variant-specific information, primarily from high-throughput functional assays, could improve both classification and cardiac event risk stratification in a large, harmonized cohort of KCNH2 missense variant heterozygotes. We quantified cell-surface trafficking of 18 796 variants in KCNH2 using a multiplexed assay of variant effect (MAVE). We recorded KCNH2 current density for 533 variants by automated patch clamping. We calibrated the strength of evidence of MAVE data according to ClinGen guidelines. We deeply phenotyped 1458 patients with KCNH2 missense variants, including QTc, cardiac event history, and mortality. We correlated variant functional data and Bayesian long QT syndrome penetrance estimates with cohort phenotypes and assessed hazard ratios for cardiac events. Variant MAVE trafficking scores and automated patch clamping peak tail currents were highly correlated (Spearman rank-order ρ=0.69; n=433). The MAVE data were found to provide up to pathogenic very strong evidence for severe loss-of-function variants. In the cohort, both functional assays and Bayesian long QT syndrome penetrance estimates were significantly predictive of cardiac events when independently modeled with patient sex and adjusted QT interval (QTc); however, MAVE data became nonsignificant when peak tail current and penetrance estimates were also available. The area under the receiver operator characteristic curve for 20-year event outcomes based on patient-specific sex and QTc (area under the curve, 0.80 [0.76-0.83]) was improved with prospectively available penetrance scores conditioned on MAVE (area under the curve, 0.86 [0.83-0.89]) or attainable automated patch clamping peak tail current data (area under the curve, 0.84 [0.81-0.88]). High-throughput KCNH2 variant MAVE data meaningfully contribute to variant classification at scale, whereas long QT syndrome penetrance estimates and automated patch clamping peak tail current measurements meaningfully contribute to risk stratification of cardiac events in patients with heterozygous KCNH2 missense variants.

Multiplexed Assays of Variant Effect and Automated Patch-clamping Improve KCNH2-LQTS Variant Classification and Cardiac Event Risk Stratification.

Long QT syndrome (LQTS) is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by KCNH2. Variant classification is difficult, often owing to lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance. Here, we sought to test whether variant-specific information, primarily from high-throughput functional assays, could improve both classification and cardiac event risk stratification in a large, harmonized cohort of KCNH2 missense variant heterozygotes. We quantified cell-surface trafficking of 18,796 variants in KCNH2 using a Multiplexed Assay of Variant Effect (MAVE). We recorded KCNH2 current density for 533 variants by automated patch clamping (APC). We calibrated the strength of evidence of MAVE data according to ClinGen guidelines. We deeply phenotyped 1,458 patients with KCNH2 missense variants, including QTc, cardiac event history, and mortality. We correlated variant functional data and Bayesian LQTS penetrance estimates with cohort phenotypes and assessed hazard ratios for cardiac events. Variant MAVE trafficking scores and APC peak tail currents were highly correlated (Spearman Rank-order ρ = 0.69). The MAVE data were found to provide up to pathogenic very strong evidence for severe loss-of-function variants. In the cohort, both functional assays and Bayesian LQTS penetrance estimates were significantly predictive of cardiac events when independently modeled with patient sex and adjusted QT interval (QTc); however, MAVE data became non-significant when peak-tail current and penetrance estimates were also available. The area under the ROC for 20-year event outcomes based on patient-specific sex and QTc (AUC 0.80 [0.76-0.83]) was improved with prospectively available penetrance scores conditioned on MAVE (AUC 0.86 [0.83-0.89]) or attainable APC peak tail current data (AUC 0.84 [0.81-0.88]). High throughput KCNH2 variant MAVE data meaningfully contribute to variant classification at scale while LQTS penetrance estimates and APC peak tail current measurements meaningfully contribute to risk stratification of cardiac events in patients with heterozygous KCNH2 missense variants.

Abstract 14613: Amyloidosis-Related Orthopedic Events, Low Plasma Transthyretin, and Risk of Cardiac Events

Introduction: Carpal tunnel syndrome, spinal stenosis, and biceps tendon rupture may precede cardiac transthyretin amyloidosis (ATTR-CA). Hypothesis: We tested the hypothesis that amyloidosis-related orthopedic events herald amyloidosis and cardiac events consistent with ATTR-CA through transthyretin destabilization. Methods: In observational analysis in the Copenhagen General Population Study (CGPS; n=93,637), we first tested whether amyloidosis-related orthopedic events at baseline were associated with amyloidosis and incident cardiac events consistent with ATTR-CA (heart failure, atrial fibrillation, myocardial infarction, or death), and whether a low plasma transthyretin was associated with a higher risk. In genetic analysis, in CGPS and the Copenhagen City Heart Study(CCHS) combined (n=102,496), we tested whether TTR genotypes associated with stepwise lower plasma transthyretin, marking lower transthyretin tetramer stability and higher amyloidogenic potential, was associated with both orthopedic and incident cardiac events, implying a common mechanistic background through transthyretin destabilization. Results: In individuals with versus without orthopedic events at baseline, hazard ratios (HRs) were 10.7 (95% CI: 3.9-29.3) for amyloidosis, and 1.3(1.1-1.4) for cardiac events. Furthermore, in individuals with orthopedic events at baseline, HRs for cardiac events were 3.8(1.9-7.6) in those with transthyretin <20 mg/dL versus ≥20 mg/dL (Figure 1). Finally, HRs as a function of TTR genotype increased with lower transthyretin and lower transthyretin tetramer stability up to 3.0(1.4-6.6) for orthopedic events and 1.6(95% CI: 1.0-2.6) for cardiac events. Conclusion: Amyloidosis-related orthopedic events are associated with increased risk of incident cardiac events, with the highest risk in those with low transthyretin levels. Orthopedic and cardiac events are linked through transthyretin tetramer destabilization.

Association of gamma-glutamyl transferase with subclinical coronary atherosclerosis and cardiac outcomes in non-alcoholics

In an asymptomatic population, we determined the relationship between serum gamma-glutamyl transferase (GGT) and subclinical atherosclerosis, using coronary computed tomography angiography (CCTA). This was a retrospective observational cohort study which analyzed 5120 consecutive asymptomatic individuals with no prior history of coronary artery disease or significant alcohol intake who voluntarily underwent CCTA as part of a general health examination. All subjects were stratified into tertiles based on GGT levels. Degree and extent of subclinical coronary atherosclerosis were evaluated using CCTA. Cardiac events were a composite of all-cause death, myocardial infarction, unstable angina, and coronary revascularization. After adjustment for cardiovascular risk factors, there were no significant differences among GGT tertiles in terms of adjusted odds ratios for non-calcified and mixed plaques. The risk of any atherosclerotic and calcified plaques, significant stenosis, multi-vessel disease, and significant stenosis in the left main or proximal left anterior descending artery was higher in the third GGT tertile than in the first tertile (all p < 0.05). Over a median 5.4-year follow-up, the third GGT tertile had significant adjusted hazards ratios for cardiac events than did the first GGT tertile, even after stepwise adjustment for cardiovascular risk factors (all p < 0.01). In asymptomatic individuals, elevated GGT was independently associated with high-risk feature atherosclerosis and poorer cardiac outcomes.

Abstract 11365: Bioelectrical Impedance Analysis is Useful for the Management of Heart Failure and Prediction of Cardiac Events in Adult Patients With Congenital Heart Disease

Introduction: Since decompensated heart failure generally leads to fluid volume overload, the ability to recognize and quantify fluid retention is critical for the treatment of heart failure. Bioelectrical impedance analysis (BIA) is a safe, non-invasive, and rapid assessment method, but little has been reported on the role of BIA in the management of patients with congenital heart disease (CHD). Hypothesis: We assessed the hypothesis that BIA is useful for the management of heart failure in adult patients with congenital heart disease. Methods: We performed a retrospective single-center study of 173 consecutive adult patients with congenital heart disease who were admitted to our institute between April 2013 and December 2015. We retrospectively reviewed the medical records of the patients to evaluate the relationship between the BIA parameters (intracellular water, extracellular water, protein, mineral, fat, edema index (EI, ratio of extracellular water to total body water)) and the laboratory values, echocardiographic parameters, and prevalence of cardiac events. Results: The patients in functional classes 3 and 4 had a higher EI compared with the patients in functional classes 1 and 2 (0.395 vs. 0.384, p &lt; 0.001). In the multivariate analysis, the EI was significantly related to serum albumin, BUN, and BNP. In addition, the reduction in body weight (BW) achieved during the hospitalization was significantly related to the reduction in EI; using a generally defined upper limit of EI as 0.39, we developed this model equation: Required BW reduction (kg) = 98.1(EI - 0.39) + 2.26(Protein) - 4.14(Mineral) - 0.04(BUN) - 1.86. During the median follow-up period of 36 months, the Kaplan-Meier analysis revealed that an EI of more than 0.39 was significantly associated with an increased prevalence of cardiac events. Using the Cox hazard model, we determined that the hazard ratio of cardiac events in patients with an EI ≧0.39 compared to patients with an EI &lt;0.39 was 3.9 (95%CI 2.0-7.9). In patients who had undergone a Fontan operation, the hazard ratio was 7.0(95%CI 1.4-77.1). Conclusions: The Edema index determined by BIA is a useful marker for the treatment of heart failure and the prediction of cardiac events in adult patients with congenital heart disease.

Early repolarization and myocardial scar predict poorest prognosis in patients with coronary artery disease.

PurposeRecent studies show positive association of early repolarization (ER) with the risk of life-threatening arrhythmias in patients with coronary artery disease (CAD). This study was to investigate the relationships of ER with myocardial scarring and prognosis in patients with CAD.Materials and MethodsOf 570 consecutive CAD patients, patients with and without ER were assigned to ER group (n=139) and no ER group (n=431), respectively. Myocardial scar was evaluated using cardiac single-photon emission computed tomography.ResultsER group had previous history of myocardial infarction (33% vs. 15%, p<0.001) and lower left ventricular ejection fraction (57±13% vs. 62±13%, p<0.001) more frequently than no-ER group. While 74 (53%) patients in ER group had myocardial scar, only 121 (28%) patients had in no-ER group (p<0.001). During follow up, 9 (7%) and 4 (0.9%) patients had cardiac events in ER and no-ER group, respectively (p=0.001). All patients with cardiac events had ER in inferior leads and horizontal/descending ST-segment. Patients with both ER in inferior leads and horizontal/descending ST variant and scar had an increased adjusted hazard ratio of cardiac events (hazard ratio 16.0; 95% confidence interval: 4.1 to 55.8; p<0.001).ConclusionER in inferior leads with a horizontal/descending ST variant was associated with increased risk of cardiac events. These findings suggest that ER in patients with CAD may be related to myocardial scar rather than pure ion channel problem.

Post-stress left ventricular ejection fraction drop in patients with diabetes: a gated myocardial perfusion imaging study

BackgroundTo evaluate the relevance of stress-induced decrease in left ventricular ejection fraction (LVEF) in patients with type-2 diabetes.MethodsA total of 684 diabetic patients with available rest and post-stress gated myocardial perfusion single-photon emission computed tomography (MPS) data were enrolled. An automated algorithm was used to determine the perfusion scores using a 17-segment model. LVEF drop was considered significant if the post-stress LVEF was ≥5% below the rest value. Follow-up data were available in 587 patients that were followed for the occurrence of cardiac death, nonfatal myocardial infarction, or unstable angina requiring revascularization.ResultsA post-stress LVEF drop ≥5% was observed in 167 (24%) patients. Patients with LVEF drop had higher summed stress score (p < 0.05), summed difference score (p < 0.001), and rest LVEF (p < 0.001) compared to patients without. Conversely, summed rest score, a measure of infarct size, was comparable between the two groups. At multivariable analysis, summed difference score and rest LVEF were independent predictors (both p < 0.001) of post-stress LVEF drop. Myocardial perfusion was abnormal in 106 (63%) patients with post-stress LVEF drop and in 296 (57%) of those without (p = 0.16). The overall event-free survival was lower in patients with post-stress LVEF drop than in those without (log rank χ2 7.7, p < 0.005). After adjusting for clinical data and MPS variables, the hazard ratio for cardiac events for post-stress LVEF drop was 1.52 (p < 0.01).ConclusionsIn diabetic patients stress-induced ischemia is an independent predictor of post-stress LVEF drop; however, a reduction in LVEF is detectable also in patients with normal perfusion. Finally, post-stress LVEF drop increases the risk of subsequent cardiac events in diabetic patients.

Fixed ratio or lower limit of normal as cut-off value for FEV1/VC: An outcome study

There is no consensus on the appropriate cut-off level for the ratio between forced expiratory volume and vital capacity (FEV(1)/VC) for the diagnosis of chronic obstructive pulmonary disease (COPD). Application of a fixed ratio of 0.7 carries the risk of false positive diagnoses in elderly subjects and false negative diagnoses in younger subjects. The use of the lower limit of normal (LLN) of an individually predicted value should eliminate this problem. There is insufficient information about the outcome of elderly subjects with an FEV(1)/VC < 0.7 but above the LLN. We report lung function (spirometry and lung clearance index, LCI), mortality and risk of cardiac events in relation to FEV(1)/VC in a population-based sample of men examined at age 55 years. We stratified subjects as having FEV(1)/VC ≥ 0.7 (N), <0.7 but > LLN (FR+) and <0.7 and <LLN (FR+LLN+). Hazard ratio for death was 1, 1.33 (0.94-1.9) and 1.71 (1.3-2.2), respectively, when adjusted for smoking and a number of cardiovascular risk factors. In contrast, there was no increase in the corrected hazard ratio for cardiac events. FEV(1) progressively declined and LCI increased from N to FR+ and FR+LLN+. Subjects with FEV(1)/VC ratio below 0.7 but above the lower limit of normal form an intermediate group with respect to lung function impairment and mortality rates. Careful evaluation of patient history and extended lung function testing may be warranted in subjects with FEV(1)/VC < 0.7 but above the lower limit of normal.

Midday naps and the risk of coronary artery disease: results of the Heinz Nixdorf Recall Study.

Several studies have assessed the association between midday nap and cardiovascular outcomes and reported heterogenous results. Concern exists that confounding might have distorted these results and contributed to discrepancies among them. This study prospectively examines the association between midday nap habits and the occurrence of coronary artery disease in a non-Mediterranean population. The baseline examination of 4,123 participants aged 45-75 years. Measurements included interviews, physical examinations, laboratory tests, and electron beam computed tomography. We studied the influence of midday nap habits on risk of coronary artery disease. We adjusted for several potential confounders including measures of subclinical atherosclerosis-such as coronary calcium score and ankle brachial index-at baseline. Cardiac events during a median follow-up of 8.1 years were defined as nonfatal myocardial infarction and sudden cardiac death. Overall, 135 of 4,123 subjects (3.3%) either suffered from acute myocardial infarction (81 subjects) or died due to a sudden cardiac death (54 subjects) during follow-up. After adjustment for several confounders including measures of subclinical atherosclerosis, regular long (> 60 min) midday nap was associated with an increased hazard ratio of cardiac events (hazard ratio 2.12, 95% confidence interval 1.11-4.05). As our detailed confounder analyses showed, confounding is not the sole explanation for this finding. Future research on midday naps should focus on biological mechanisms that may be responsible for increasing the risk of coronary artery disease among subjects taking regular long midday naps.

Use of Rivastigmine or Galantamine and Risk of Adverse Cardiac Events: A Database Study from the Netherlands

BackgroundTwo cholinesterase inhibitors (ChEIs), rivastigmine and galantamine, are used to treat Alzheimer disease in the Netherlands. Several adverse cardiac events have been reported for these medications. ObjectiveWe aimed to assess if the use of ChEIs increased the risk of cardiac events in the Netherlands. MethodsA cohort crossover study of the PHARMO Record Linking System database included patients who initiated ChEIs at age 50 years or older, had at least 1 dispensing of a ChEI drug between 1998 and 2008, a 1-year history in PHARMO, and 1 subsequent dispensing of any medication. Two outcomes were assessed: a first hospitalization for syncope or atrioventricular block. Poisson and Cox regression were used to calculate incidence densities and hazard ratios for cardiac events during periods with ChEI use, compared with periods without ChEI use. ResultsDuring the complete observation period of 8.9 years (interquartile range 6.7 to 10.2) there were 132 first hospitalizations for atrioventricular block and 17 first hospitalizations for syncope among 3358 patients. The adjusted incidence densities were significantly increased during ChEI exposure for syncope and atrioventricular block, when compared with the background incidence densities in the roughly 5 years before the last year before ChEI initiation. However, when exposed periods were compared with the unexposed periods 1 year before ChEI initiation and times after exposure, the adjusted hazard ratios remained increased for syncope and atrioventricular block, but increases were not significant anymore. ConclusionsExposure to ChEIs might increase the risk of adverse cardiac events, but small numbers of cases limit conclusions about the risk in this population and research on larger study samples is needed.

Early repolarization pattern predicts cardiac death and fatal arrhythmia in patients with vasospastic angina

BackgroundEarly repolarization (ER), which is characterized by an elevation of J-point, is sometimes associated with fatal arrhythmia and sudden cardiac death in patients without structural heart disease. This study investigated the prevalence and prognostic significance of ER in patients with vasospastic angina (VA). MethodsWe assessed the ER pattern in 281 VA patients (mean age, 50.5±7.9years), and the prognostic modulation of ER-associated risk by ST-segment variations. ResultsAny type of ER≥0.1mV in inferior and/or lateral leads was persistently observed after chest pain in 60 (21.4%) VA patients. During the follow up period of 7.6±4.7years, patients with ER had higher incidence of cardiac events including cardiac death, aborted sudden cardiac death or fatal arrhythmia than those with no ER (20.0% vs. 5.4%, p=0.001). Patients with ER≥0.1mV and horizontal/descending ST variant (n=18) had an increased age- and sex-adjusted hazard ratio of cardiac events (relative risk 8.12; 95% confidence interval 3.45–19.12). When modeled for ER in inferior leads and horizontal/descending ST-segment variant, the hazard ratio of cardiac events increased to 8.89 (95% confidence interval 3.78–20.91). However, in subjects with ascending ST variant, the relative risk for arrhythmic death was not significantly increased. ConclusionER was observed in a fifth of VA patients, and was associated with an increased risk of cardiac events in VA. However, it is also possible that, in patients with ER, VA might cause an adverse event or facilitate the diagnosis of ER.

Urinary 8-Hydroxy-2'-Deoxyguanosine as a Novel Biomarker for Predicting Cardiac Events and Evaluating the Effectiveness of Carvedilol Treatment in Patients With Chronic Systolic Heart Failure

The authors recently reported that urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) derived from cardiac tissue reflects clinical status and cardiac dysfunction severity in patients with chronic heart failure (CHF). The aim of the present study was to investigate whether U8-OHdG levels can accurately predict cardiac events in CHF patients and their response to β-blocker treatment. Plasma brain natriuretic peptide (BNP) and U8-OHdG levels were measured in 186 consecutive CHF patients before discharge. Patients were then prospectively followed (median follow-up, 649 days) with endpoints of cardiac death or hospitalization due to progressive heart failure. From receiver operating characteristic curve analysis, cut-offs were 12.4ng/mg creatinine (Cr) for U8-OHdG and 207pg/ml for BNP. On multivariate Cox analysis, U8-OHdG and BNP were independent predictors of cardiac events. Patients were classified into 4 groups according to U8-OHdG and BNP cut-offs. The hazard ratio for cardiac events in patients with BNP ≥207pg/ml and U8-OHdG ≥12.4ng/mg Cr was 16.2 compared with approximately 4 for patients with only 1 indicator above its respective cut-off. Furthermore, carvedilol therapy was initiated in 30 CHF patients. In responders (≥10% increase in left ventricular ejection fraction [LVEF] or ≥1 class decrease in New York Heart Association [NYHA] class), U8-OHdG levels decreased significantly along with improved NYHA class, LVEF, and BNP levels after treatment. U8-OHdG may be a useful biomarker for predicting cardiac events and evaluating β-blocker therapy effectiveness in CHF patients.

Progression of coronary artery calcification and cardiac events in patients with chronic renal disease not receiving dialysis

We tested for the presence of coronary calcifications in patients with chronic renal disease not on dialysis and studied its progression in 181 consecutive non-dialyzed patients who were followed for a median of 745 days. Coronary calcifications (calcium score) were tallied in Agatston units by computed tomography, and the patients were stratified into two groups by their baseline calcium score (100 U or less and over 100 U). Survival was measured by baseline calcium score and its progression. Cardiac death and myocardial infarction occurred in 29 patients and were significantly more frequent in those patients with calcium scores over 100 U (hazard ratio of 4.11). With a calcium score of 100 U or less, the hazard ratio for cardiac events was 0.41 and 3.26 in patients with absent and accelerated progression, respectively. Thus, in non-dialyzed patients, the extent of coronary calcifications was associated to cardiac events, and progression was an independent predictive factor of cardiac events mainly in less calcified patients. Hence, assessment of coronary calcifications and progression might be useful for earlier management of risk factors and guiding decisions for prevention of cardiac events in this patient population.

Serum Cortisol as a Useful Predictor of Cardiac Events in Patients With Chronic Heart Failure

Background— The pathophysiological role of cortisol, which binds to the mineralocorticoid receptor with an affinity equal to that of aldosterone (ALD), may be influenced by oxidative stress in patients with chronic heart failure. We evaluated cardiac event prediction using cortisol levels in chronic heart failure, in comparison with ALD, adrenocorticotropic hormone, and brain natriuretic peptide (BNP), and the impact of oxidative stress. Methods and Results— We measured the plasma levels of biomarkers such as BNP, ALD, adrenocorticotropic hormone, serum cortisol, and oxidized low-density lipoprotein (oxLDL), a biomarker of oxidative stress, in 319 consecutive symptomatic patients with chronic heart failure, and we followed these patients for a mean period of 33 months. During the follow-up period, 29 patients had cardiac events (death or hospitalization). Plasma levels of BNP, ALD, adrenocorticotropic hormone, oxLDL, and serum cortisol (16.8�1.8 μg/dL versus 12.4�0.3 μg/dL, P =0.01) were significantly higher in patients with cardiac events than in those without cardiac events. On stepwise multivariate analyses, high levels of BNP ( P =0.0003), renin ( P =0.002), cortisol ( P =0.02), and oxLDL ( P =0.002) were independent predictors of cardiac events, but ALD and adrenocorticotropic hormone levels were not. In patients with serum cortisol ≥12.5 μg/dL, the hazard ratio of cardiac events in patients with oxLDL ≥12 U/mL was 3.5 compared with that in patients with oxLDL &lt;12 U/mL ( P =0.008). Conclusions— These findings indicate that serum cortisol levels were a complementary and incremental cardiac event risk predictor in combination with BNP in patients with chronic heart failure and that cardiac event prediction based on cortisol levels was influenced by oxidative stress.

Coronary Artery Bypass Grafting Versus Coronary Implantation of Sirolimus-Eluting Stents in Patients with Diabetic Retinopathy

We compared the 1-year outcome of coronary revascularization with sirolimus-eluting stents (SESs) or coronary artery bypass grafting (CABG) for coronary artery disease involving the left anterior descending artery (LAD) in diabetic patients according to their retinal status: no diabetic retinopathy (NDR) and diabetic retinopathy (DR). Between April 2004 and October 2005, 220 consecutive patients with coronary artery disease involving the LAD underwent implantation of SESs; of these, 25 patients had NDR and 54 had DR. For each group, we included a comparison group of diabetic patients who had undergone CABG and had the same retinal status. During 1 year after revascularization, five cardiac events (cardiac death, myocardial infarction, and repeat revascularization) were noted in NDR-SES patients, four in NDR-CABG, 24 in DR-SES, and eight in DR-CABG patients. Most cardiac events were repeat revascularizations. Kaplan-Meier estimates of the incidence of cardiac events at 1 year were 21.1%, 11.4%, 44.0%, and 14.0%, respectively. Kaplan-Meier curves for cardiac events in SES patients were different from those of CABG patients for the DR group (p = 0.003), but not NDR groups. After adjustments for the potential confounders, the hazard ratio of cardiac events in DR-SES patients was 2.8 (95% confidence interval, 1.1 to 6.9; p = 0.02). Compared with SES implantation, CABG is more suitable for revascularization in patients with coronary artery disease involving the LAD and DR.

Abstract 2913: Persistently Increased Serum Concentrations Of Heart-type Fatty Acid-binding Protein Predict Adverse Outcomes In Patients With Chronic Heart Failure

Background: H-FABP is a small cytosolic protein and released into the circulation when the myocardium is injured. We previously demonstrated that H-FABP level at admission was a novel marker for myocardial cell injury and prognosis in CHF patients. In this study we examined whether serial measurements of H-FABP levels provide additional prognostic information. Methods: We measured serum H-FABP levels at both admission and discharge in 112 CHF patients, and patients were followed up (mean 686 days) to register cardiac events. Cut off value for H-FABP was determined from ROC curve in previous studies. Results: The median H-FABP level was 7.4 ng/ml at admission and 4.9 ng/ml at discharge. The following 3 patterns of changes in H-FABP levels were identified. In 41 patients, H-FABP levels (&lt; 4.3 ng/ml) at both admission and discharge were normal (Group 1). The remaining 71 patients had high initial H-FABP levels (≥ 4.3 ng/ml) at admission. In 20 of these 71 patients (28%), H-FABP decreased to normal range at discharge (Group 2), whereas 51 had persistently high H-FABP levels despite improvement in symptoms and signs of CHF (Group 3). There were 32 cardiac events (29%) during a follow-up period. Kaplan-Meier analysis demonstrated that Group 3 had significantly higher cardiac event rates than Groups 1 and 2 (Figure A ). A stepwise Cox regression analysis also demonstrated that Group 3 was associated with the highest cardiac event risk among 3 groups (hazard ratio 5.68, P = 0.012) (Figure B ). Conclusion: These results suggest that serial measurements of H-FABP levels are a new monitoring tool, which provides helpful information to guide optimal therapy and manage CHF patients. [A] Comparison of cardiac event rates among 3 groups [B] Hazard ratio of cardiac events among 3 groups

N-terminal Pro B-type Natriuretic Peptide Predicts Cardiac Events in Discharged Patients with Idiopathic Dilated Cardiomyopathy

Background and Objectives:Heart failure is a progressive chronic disease with high morbidity and mortality. The aim of this study was to determine whether the N-terminal pro B-type natriuretic peptide (NT-proBNP) levels in the blood can predict readmission due to heart failure or cardiac death (cardiac event) following hospital discharge, and if these are a better predictive marker than a pre-discharge echocardiogram or other laboratory parameters in discharged patients with idiopathic dilated cardiomyopathy (DCM). Subjects and Methods:The outcomes of 36 patients with idiopathic DCM, diagnosed on hospital admission, were retrospectively evaluated. Results:During a mean follow-up period of 520 days, a 22.2% rate of cardiac events was observed. Evaluation of the NT-proBNPs showed the mid-term (mean 84 day after discharge) outpatient (OPD) NT-proBNP levels to be a strong predictor of cardiac events, with an area under the curve analysis of 0.90. The optimal mid-term OPD NT-proBNP cut-off level for predicting cardiac events was 1500 pg/mL, with a sensitivity and specificity of 80 and 92%, respectively; patients with levels above this threshold had a 22.9 hazard ratio for cardiac events compared to those with levels below this threshold. Conclusion:The mid-term OPD plasma NT-proBNP levels were able to predict cardiac events in discharged patients with idiopathic DCM, regardless of the admission or predischarge NT-proBNP levels and other laboratory parameters. The measurement of OPD NT-proBNP at the mid term follow-up may be useful in outpatient therapeutic monitoring or for the development of prognostic guidelines in patients with idiopathic DCM. (Korean Circulation J 2007;37:202-207)

Prognostic value of lipoprotein fractions in essential hypertension

Background: To evaluate distribution and prognostic value of total cholesterol and lipoprotein fractions in essential hypertension. Methods: In a prospective cohort study, 2649 initially untreated subjects with essential hypertension (aged 51, 46.5% women) were investigated at entry and followed for a mean of 5.6 years (range: 1-16). Results: At entry, subjects with total cholesterol (TC) ≥240 mg/dl (≥6.22 mmol/l) or high-density lipoprotein (HDL) cholesterol (HDL-C) <40 mg/dl (1.05 mmol/l) or low-density lipoprotein (LDL) cholesterol (LDL-C) ≥160 mg/dl (4.13 mmol/l) or TC/HDL-C ratio >6 were 47.7%. TC, HDL-C, LDL-C and triglycerides (TG) did not show any association with office or 24-h ambulatory blood pressure (BP). During follow-up there were 167 first cardiac events and 122 first cerebrovascular events. TC, HDL-C, LDL-C and TC/HDL-C ratio showed an association with cardiac events, but not with cerebrovascular events. TG did not show any association with cardiac or cerebrovascular events. After adjustment for age, sex, diabetes, smoking, left ventricular (LV) hypertrophy and 24-h pulse pressure, the hazard ratio for cardiac events was 1.83 (95% CI 1.23-2.71) in association with a TC ≥6.22 mmol/l, 2.23 with a HDL-C <1.05 mmol/l (95% CI 1.06-4.70), 2.83 with a LDL-C ≥4.91 mmol/l (95% CI 1.48-5.42) and 3.90 with a TC/HDL-C ratio >6.0 (95% CI 2.23-6.81). When forced in the same model, HDL-C and LDL-C showed an independent association with cardiac events. Conclusions: Abnormalities of TC and lipoproteins are common in essential hypertension. HDL-C and LDL-C independently predict the risk of cardiac, but not cerebrovascular, events. Their predictive value is independent of several confounding factors including LV hypertrophy and ambulatory BP.