Atypical familial dysbetalipoproteinemia associated with high polygenic cholesterol and triglyceride scores treated with ezetimibe and evolocumab.

We present a 37-year-old man diagnosed with familial dysbetalipoproteinemia who presented with the severe hyperlipidemic phenotype. None of the usual metabolic triggers were found to explain his severe lipid abnormalities. Genetic analysis revealed the expected APOE E2/E2 genotype, but no other mutations were found to explain any monogenic dyslipidemia or syndrome. Polygenic risk scores for quantitative lipid traits did reveal scores placing the patient in the >99th percentile for the general population concerning polygenic susceptibility for both high cholesterol and triglycerides. Owing to his gastrointestinal intolerance to two high-intensity statins, he was treated with both ezetimibe 10 mg a day and evolocumab 140 mg subcutaneously every 2 weeks. All measures of potentially atherogenic lipids were markedly improved and remained so for more than 10 months of follow-up. This case report shows an unusual trigger for severe hyperlipidemia with familial dysbetalipoproteinemia and a favorable therapeutic response to the combination of ezetimibe and evolocumab.

The Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Nonfasting Remnant Cholesterol in a Real World Population.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have demonstrated significant effects on low-density lipoprotein (LDL) cholesterol and nonhigh density lipoprotein (HDL) cholesterol. To date, there have been limited reports on the effect of PCSK9 inhibitors on remnant cholesterol. OBJECTIVES: Assess the effect of PCSK9 inhibitors on nonfasting remnant cholesterol in a real world population. Identify whether pretreatment triglyceride levels are associated with PCSK9 inhibition success as indicated by changes in remnant cholesterol levels. METHODS: Patients in our adult lipid clinic (n = 109) receiving PCSK9 inhibition for atherosclerotic cardiovascular disease or familial hypercholesterolemia who had available pre- and post-PCSK9 inhibition standard nonfasting lipid data were, retrospectively, selected for data analysis. Remnant cholesterol was the difference between non-HDL and LDL cholesterol. LDL cholesterol was measured directly and calculated from Friedewald and Martin/Hopkins methods. Data were analyzed using repeated measures ANOVA and multivariable linear regression for differential effects on remnant and LDL cholesterol based upon pretreatment nonfasting triglyceride levels. RESULTS: Remnant cholesterol as well as total, LDL, non-HDL cholesterol, and triglycerides decreased significantly (P<0.001) after PCSK9 inhibition. Patients with higher pretreatment triglyceride levels showed greater decrease in remnant cholesterol after PCSK9 inhibition (P<0.001) than those with lower pretreatment triglycerides. CONCLUSIONS: In patients receiving PCSK9 inhibitors, remnant cholesterol as determined from nonfasting blood was reduced in proportion to pretreatment triglycerides.

Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association.

The management of low-risk patients presenting to emergency departments is a common and challenging clinical problem entailing 8 million emergency department visits annually. Although a majority of these patients do not have a life-threatening condition, the clinician must distinguish between those who require urgent treatment of a serious problem and those with more benign entities who do not require admission. Inadvertent discharge of patients with acute coronary syndrome from the emergency department is associated with increased mortality and liability, whereas inappropriate admission of patients without serious disease is neither indicated nor cost-effective. Clinical judgment and basic clinical tools (history, physical examination, and electrocardiogram) remain primary in meeting this challenge and affording early identification of low-risk patients with chest pain. Additionally, established and newer diagnostic methods have extended clinicians' diagnostic capacity in this setting. Low-risk patients presenting with chest pain are increasingly managed in chest pain units in which accelerated diagnostic protocols are performed, comprising serial electrocardiograms and cardiac injury markers to exclude acute coronary syndrome. Patients with negative findings usually complete the accelerated diagnostic protocol with a confirmatory test to exclude ischemia. This is typically an exercise treadmill test or a cardiac imaging study if the exercise treadmill test is not applicable. Rest myocardial perfusion imaging has assumed an important role in this setting. Computed tomography coronary angiography has also shown promise in this setting. A negative accelerated diagnostic protocol evaluation allows discharge, whereas patients with positive findings are admitted. This approach has been found to be safe, accurate, and cost-effective in low-risk patients presenting with chest pain.

Left ventricular noncompaction: a rare disorder in adults and its association with 1p36 chromosomal anomaly.

We report on a case of a 25-year-old male with 1p36 deletion syndrome, who was diagnosed with left ventricular noncompaction (LVNC). The association of this rare chromosomal abnormality with LVNC is reported in the pediatric literature, but it has not previously been specifically reported in adults. It is important to diagnose this unclassified cardiomyopathy in the adult population with this chromosomal abnormality for appropriate management and treatment as highlighted in our case.

A pretest prognostic score to assess patients undergoing exercise or pharmacological stress testing.

OBJECTIVE: A previously developed pretest score was validated to stratify patients presenting for exercise testing with suspected coronary disease according to the presence of angiographic coronary disease. Our goal was to determine how well this pretest score risk stratified patients undergoing pharmacological and exercise stress tests concerning prognostic endpoints. DESIGN: Retrospective cohort analysis. SETTING: University hospital stress laboratory. PATIENTS: 7452 unselected ambulatory patients with symptoms of suspected coronary disease undergoing stress testing between 1995 and 2004. MAIN OUTCOMES MEASURES: All-cause death, cardiac death and non-fatal myocardial infarction. RESULTS: The rate of all-cause death was 5.5% (CI 5.0 to 6.1) with 4.3 (SD 2.4) years of follow-up (Exercise 2.8% (CI 2.3 to 3.2) v Pharmacological group 11.9% (CI 10.5 to 13.3); p<0.001). The rate of cardiac death/myocardial infarction was 2.6% (CI 2.2 to 3.0) (Exercise 1.4% (CI 1.1 to 1.8) v Pharmacological group 5.3% (CI 4.3 to 6.2); p<0.001). In both groups, stratification by pretest score was significant for all-cause death and the combined endpoint. However, stratification was more effective in the pharmacological group using the combined endpoint rather than all-cause death. Pharmacological stress patients in intermediate and high risk groups were at higher risk than their respective exercise test cohorts. Referral for pharmacological stress testing was found to be an independent predictor of time to death (2.7 (CI 2.0 to 3.6); p<0.001). CONCLUSION: A pretest score previously validated to stratify according to angiographic outcomes, effectively risk stratified pharmacological and exercise stress patients according to the combined endpoint of cardiac death/myocardial infarction.

Assessment of estrogen status as a marker of prognosis in women with symptoms of suspected coronary artery disease presenting for stress testing.

Estrogen status (ES) has previously been shown to be a marker of angiographic outcome in women. In light of this finding, a reevaluation of ES as a marker of prognosis was undertaken. Two thousand one hundred forty-three women who underwent stress testing for symptoms of suspected coronary disease were studied. ES was defined according to menopausal, ovarian, and hormone replacement therapy status. The end points of interest were all-cause mortality, cardiac death, and nonfatal myocardial infarction. Survival analysis was performed using the Kaplan-Meier method and Cox regression analysis with censoring at revascularization. Compared with 1,362 ES-positive women, the 781 ES-negative women had a higher frequency of unfavorable end points (all-cause death: ES positive 31 [2.3%] vs ES negative 94 [12%], p < 0.0001, cardiac death: ES positive 11 [0.8%] vs ES negative 38 [4.9%], p < 0.0001, and nonfatal myocardial infarction: ES positive 11 [0.8%] vs ES negative 17 [2.2%], p = 0.007). The Kaplan-Meier curve analysis indicated that ES was a marker of cardiac risk (p < 0.0001) in all women, as well as in postmenopausal women. Multivariate Cox regression analysis revealed that ES was an independent marker of risk (p < 0.001) when considered with other standard risk factors. Using logistic regression and area under the curve analyses, ES had incremental value compared with standard risk factors. In conclusion, ES appears to be an easily discernible independent marker of risk that provides incremental prognostic information compared with standard clinical variables in women with symptoms of suspected coronary disease presenting for stress testing.

Can we reliably predict long-term mortality after exercise testing? An external validation.

OBJECTIVE: The aim of the study was to derive and externally validate a mortality prediction rule for patients undergoing exercise testing. BACKGROUND: The prognostic value of exercise testing is increasingly appreciated. However, global prognosis estimates ideally should account for numerous routinely obtained variables, including demographics, risk factors, resting electrocardiogram, and multiple exercise test measures. METHODS: A prediction rule was derived by parametric hazards modeling on a derivation set of 46047 Cleveland Clinic patients (age 55 +/- 11 years, 67% male) who had no history of heart failure, valve disease, or atrial fibrillation. Twenty-two variables covering demographics, risk factors, exercise hemodynamics, and electrocardiogram findings at rest and during exercise were considered. The resulting model included 16 variables and was tested on 4981 patients (age 50 +/- 12 years, 55% male) who underwent exercise testing at West Virginia University. RESULTS: In the derivation cohort there were 3173 deaths during a mean of 7 years of follow-up, whereas in the validation cohort there were 180 deaths during a mean of 5 years of follow-up. Comparisons of predicted and observed death rates showed very good agreement among all patients across all spectrums of risk, as well as among prespecified high-risk subgroups. Model discrimination was also good, with c statistic of c = 0.79 in the derivation group and c = 0.81 in the validation cohort. CONCLUSIONS: We have externally validated a mortality prediction rule for patients undergoing exercise testing and confirmed its accuracy among a wide spectrum of patients.

Primary percutaneous balloon pericardiotomy.

Percutaneous balloon pericardiotomy was reported by Palacious et al in 1991. From 1996-2000, we utilized this procedure as the initial treatment for 17 patients at West Virginia University Hospital in Morgantown with cardiac tamponade who had a high likelihood of recurrence of pericardial effusion. Primary pericardiotomy was successful after the initial procedure in 82% (n = 14) of these patients, so it appears to be an effective non-surgical procedure for patients at high risk for re-accumulation of pericardial effusions. In addition, our comparison at this institution revealed that primary percutaneous pericardial window creation is significantly less costly than pericardiocentesis followed by surgical pericardial window creation.

Validation of the accuracy of pretest and exercise test scores in women with a low prevalence of coronary disease: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study.

BACKGROUND: Recently revised American College of Cardiology/American Heart Association guidelines have suggested that exercise test scores be used in decisions concerning patients with suspected coronary artery disease (CAD). Pretest and exercise test scores derived for use in women without known CAD have not been tested in women with a low prevalence of CAD. METHODS: Within the Women's Ischemia Syndrome Evaluation (WISE) study, we evaluated 563 women undergoing coronary angiography for suspected myocardial ischemia. The prevalence of angiographic CAD was 26%. Overall, 189 women underwent treadmill exercise testing. Prognostic end points included death, myocardial infarction, stroke, and revascularization. RESULTS: Each score stratified women into 3 probability groups (P <.001) according to the prevalence of coronary disease: Pretest: low 20/164 (12%), intermediate 53/245 (22%), high 75/154 (49%); Exercise test: low 11/83 (13%), intermediate 22/74 (30%), high 17/32 (53%). However, the Duke score did not stratify as well: low 7/46 (15%), intermediate 36/126 (29%), high 6/17 (35%); P =.44. When pretest and exercise scores were considered together, the best stratification with the exercise test score was in the intermediate pretest group (P <.03). The Duke score did not stratify this group at all (P =.98). Pretest and exercise test scores also stratified women according to prognostic end points: pretest--low 7/164 (4.3%), intermediate 28/245 (11.4%), high 27/154 (17.5%), P <.01; exercise test--low 4/83 (4.8%) and intermediate-high 17/106 (16%), P =.014. CONCLUSION: Both pretest and exercise test scores performed better than the Duke score in stratifying women with a low prevalence of angiographic CAD. The exercise test score appears useful in women with an intermediate pretest score, consistent with American College of Cardiology/American Heart Association guidelines.

Carbon monoxide poisoning: a case report of reversible cardiormyopathy.

Acute carbon monoxide poisoning is the most common cause of poison-related deaths in the U.S. A 21-year-old white woman was referred to Ruby Memorial Hospital after exposure to carbon monoxide (CO) from a faulty furnace. She developed acute weakness, dyspnea, nausea and vomiting. An electrocardiogram revealed sinus tachycardia, non-specific ST-T wave abnormalities, and a prolonged QTc interval. The chest X-ray revealed pulmonary edema and the 2-D echocardiography revealed decreased left ventricular systolic function with an ejection fraction of 25%. She was treated with high-flow oxygen and supportive medical therapy with complete resolution of the left ventricular dysfunction six weeks later. She has been followed for over one year without medical therapy and without recurrence of her symptoms. This case illustrates that the depressant effect of CO poisoning on the myocardium can be reversed in the short term with supportive medical therapy and recovery sustained in the long term without medical therapy.

Evaluation of pretest and exercise test scores to assess all-cause mortality in unselected patients presenting for exercise testing with symptoms of suspected coronary artery disease.

OBJECTIVES: To determine how well recently developed multivariables scores assess for all-cause mortality in patients with suspected coronary disease presenting for exercise electrocardiography (ExECG). BACKGROUND: Recently revised American College of Cardiology/American Heart Association guidelines for ExECG have suggested that ExECG scores be used to assist in management decisions in patients with suspected coronary artery disease. Recently developed scores accurately stratify patients according to angiographic disease severity. METHODS: To determine how well these scores assess for all-cause mortality, we utilized 4,640 patients without known coronary disease who underwent ExECG to evaluate symptoms of suspected coronary disease between 1995 and 2001. Previously validated pretest and exercise test scores as well as the Duke treadmill score were applied to each patient. All-cause mortality was our end point. RESULTS: Overall mortality was 3.0% with 2.8 +/- 1.6 years of follow-up. All three scores stratified patients into low-, intermediate-, and high-risk groups (p < 0.00001). No differences were seen when patients were evaluated as subgroups according to gender, diabetes, beta-blockers, or inpatient status. Low-risk patients defined by the Duke treadmill score had consistently higher mortality and absolute number of deaths compared with low-risk patients using other scores. In addition, the Duke treadmill score had less incremental stratifying value than the new exercise score. CONCLUSIONS: Simple pretest and exercise scores risk-stratified patients with suspected coronary disease in accordance with published guidelines and better than the Duke treadmill score. These results extend to diabetics, inpatients, women, and patients on beta-blockers.

Development and validation of a simple exercise test score for use in women with symptoms of suspected coronary artery disease.

BACKGROUND: Recently revised American College of Cardiology/American Heart Association guidelines for exercise electrocardiography (ExECG) have suggested that ExECG scores be used to assist in management decisions in patients with suspected coronary artery disease (CAD). METHODS: We used 442 women who underwent both ExECG and coronary angiography (CAD > or =1 lesion with > or =50% stenosis; CAD prevalence was 32%) to derive an ExECG score including clinical and ExECG variables. By use of logistic regression analysis, variables were selected and relative weights were determined. Variable codes multiplied by respective weights were summed to produce a final ExECG score. The score was validated in separate populations concerning angiographic as well as prognostic end points. RESULTS: Clinical variables selected and their weights included age (5), symptoms (2), diabetes (2), smoking (2), and estrogen status (1). ExECG variables selected and their weights included ST depression (2), exercise heart rate (4), and Duke Angina Index (3). For the validation group, score ranges are shown with the prevalence of CAD: <20 = 0/5 or 0%, 20-29 = 3/26 or 11%, 30-39 = 20/56 or 36%, 40-49 = 33/81 or 41%, 50-59 = 24/49 or 49%, 60-69 = 22/32 or 69%, and >70 = 7/7 or 100%. Frequency of death within 3 predetermined subgroups was as follows: low <40 = 3/1237 (0.2%), intermediate 40-60 = 9/383 (2.3%), high >60 = 4/54(7%); P<.0001. CONCLUSION: A simple ExECG score was developed for use specifically in women. When evaluated in separate cohorts, the score stratified women with suspected coronary disease into groups with a gradually increasing frequency of coronary disease and death.

What percent luminal stenosis should be used to define angiographic coronary artery disease for noninvasive test evaluation?

BACKGROUND: There has been controversy over what is the best angiographic luminal dimension criterion associated with ischemia for evaluating diagnostic tests. If one assumes that ST-segment depression or scores are indicators of ischemia, then whatever angiographic criteria best discriminates those with ischemic and nonischemic responses would be the best angiographic marker for ischemia. To study this, we calculated the area under the ROC curves for ST depression and scores at different angiographic cut-points in order to determine the best angiographic cut-point for defining ischemia-producing coronary disease. METHODS: Twelve hundred and seventy-six consecutive males without prior MI with a mean age of 59 +/- 11 years who had undergone exercise testing and coronary angiography were analyzed in this study. We calculated the number of patients of this population that would be considered to have coronary artery disease at different cut-points for angiographic luminal stenosis. For example, 59% of the patients had significant CAD when disease was defined as 50% or greater coronary lumen stenosis of any coronary vessel while 49% of the patients had significant CAD when disease was defined as 70% or greater coronary lumen stenosis. Cut-points were considered between 40 to 100% coronary lumen stenosis. ROC analysis was then performed comparing ST depression and treadmill scores at each of these cut-points. RESULTS: The cut-point for coronary lumen stenosis that returned the highest AUC for ST depression and scores was between 70 and 80% coronary luminal stenosis. However, the difference between the 50% and 75% luminal stenosis criteria was minimal. CONCLUSION: It appears that the best cut-point for defining significant angiographic disease when evaluating diagnostic tests of ischemia is 75% or greater coronary luminal stenosis.

Value of a simple measure of estrogen status for improving the diagnosis of coronary artery disease in women.

PURPOSE: To determine the potential impact of estrogen status on the pretest and postexercise test diagnostic accuracy of exercise testing. PATIENTS AND METHODS: The study comprised a total of 234 women and 326 men who underwent exercise testing followed by coronary angiography. We performed incremental logistic regression analysis of pretest (age, symptoms, smoking, diabetes, cholesterol level) with and without estrogen status (defined according to menopausal and oral estrogen status) and exercise test (two ST-segment and three non-ST-segment) variables separately for men and women. Outcomes were assessed by receiver operating characteristic (ROC) curve area analysis. RESULTS: Estrogen status was an independent pretest predictor of angiographic coronary disease. Pretest ROC curve areas: women without estrogen status = 0.79, women with estrogen status = 0.85, men = 0.78 (women with estrogen status versus other groups, p < 0.001). Postexercise test ROC curve areas: women without estrogen status = 0.83, women with estrogen status = 0.87, men = 0.88 (women without estrogen status versus other groups, p < 0.001). CONCLUSION: Consideration of estrogen status allowed for a significant improvement in the pretest clinical diagnosis of coronary disease in women. When these improvements were added to the results of exercise testing, the diagnostic accuracy of the combined clinical and exercise test data was similar for men and women. Estrogen status may be an important diagnostic clinical variable in women with suspected coronary disease.