Spectrum of radionuclide perfusion study abnormalities in takotsubo cardiomyopathy.

BACKGROUND: Takotsubo (stress) cardiomyopathy (TCM) is characterized by transient apical left ventricular dysfunction precipitated by emotional or physical stress. Its presentation makes it difficult to differentiate from an acute coronary syndrome. A suggestive echocardiogram plus normal coronary angiography most often are used for diagnosis. Radionuclide perfusion study (RPS) findings in TCM, including by positron emission tomography (PET), have been poorly characterized. METHODS AND RESULTS: Intermountain Healthcare electronic medical records were searched from 2009 to 2019 for patients with a discharge diagnosis of TCM, stress CM, or takotsubo syndrome. 16 TCM patients with an RPS, including by PET in 8, were identified: 13 (81%) were women; age averaged 72 years (50-89 years); 14 had an identified stressor. TCM diagnosis was definite in 11 and probable/possible in 5. RPS was abnormal in 11, with 9 showing an apical perfusion deficit, whereas angiography in 14 showed normal coronaries in 12 and non-obstructive disease in 2. Echo ejection fraction averaged 41% (29%-60%); an apical wall motion abnormality was present in 14 (88%). Troponin elevations were noted in 14/15. The presenting ECG was abnormal is 14, frequently showing ST-T-wave abnormalities. 13 patients were discharged on a beta-blocker. Follow-up echo (in 12) showed recovered ejection fraction in 9 and recovered apical wall motion in 11. CONCLUSIONS: Despite having normal or non-obstructive epicardial coronary arteries on angiography, TCM patients frequently present with apical wall motion abnormalities and matching RPS perfusion defects. These findings suggest microvascular abnormalities, whose pathophysiology, temporal course, and clinical implications should be the subject of further investigation.

Comparison of Three Atherosclerotic Cardiovascular Disease Risk Scores With and Without Coronary Calcium for Predicting Revascularization and Major Adverse Coronary Events in Symptomatic Patients Undergoing Positron Emission Tomography-Stress Testing.

Atherosclerotic cardiovascular disease (ASCVD) is the most important cause of morbidity and mortality nationally and internationally. Improving ASCVD risk prediction is a high clinical priority. We sought to determine which of 3 ASCVD risk scores best predicts the need for revascularization and incident major adverse coronary events (MACE) in symptomatic patients at low-to-intermediate primary ASCVD risk referred for regadenoson-stress positron emission tomography (PET). Risk scores included the standard ASCVD pooled cohort equation (PCE), the multiethnic study of atherosclerosis (MESA) risk equation, and the coronary artery calcium score (CACS), obtained by PET. All qualifying patients in our institution at primary ASCVD risk referred for PET-stress tests in whom PCE, MESA, and CAC scores could be calculated were studied. CACS categories were: 0, 1 to 10, 11 to 299, 300 to 999, and 1000+. MESA and PCE scores were divided into quartiles. Logistic regression modeling was used to predict clinical/PET-driven early revascularization (within 90 days) and 1-year MACE (death, myocardial infarction, or any-time revascularization). A total of 981 patients (54% men, age 67 ± 10 years) qualified and were studied. Scores including CAC (MESA, CACS) performed better than PCE for predicting overall 1-year MACE (MESA p <0.001, CACS p = 0.012 vs PCE), which was driven by early revascularization. In conclusion, in a large population of patients at primary ASCVD risk referred for PET-stress testing, risk scores including CAC (CACS, MESA), which better predicted early revascularization and 1-year MACE, may be particularly useful in primary coronary risk assessment when considering whom to refer for PET-stress testing.

Statins for primary prevention of cardiovascular disease: the benefits outweigh the risks.

PURPOSE OF REVIEW: Statins significantly reduce cardiovascular morbidity and mortality in patients with and without coronary heart disease. Recently, much debate has focused on use of statins for primary prevention following a class-wide safety label change by the US Food and Drug Administration amidst concerns of worsened hyperglycemia. Here, we review the evidence for statins in primary prevention and offer guidance for their appropriate use. RECENT FINDINGS: Two meta-analyses published since 2012 unequivocally support statins for primary prevention. Data from the Cholesterol Treatment Trialists' Collaborators demonstrated a 9% [relative risk (RR) 0.91, 95% confidence interval (CI) 0.85-0.97] reduction in all-cause mortality and a 25% (RR 0.75, 95% CI 0.70-0.80) reduction in major vascular events per 1.0 mmol/l reduction in low-density lipoprotein cholesterol, even among low-risk patients. A 2013 Cochrane review corroborated these findings including a 14% (OR 0.86, 95% CI 0.79-0.94) reduction in all-cause mortality and a 25% (RR 0.75, 95% CI 0.70-0.81) reduction in cardiovascular disease events with statin therapy despite an 18% (RR 1.18, 95% CI 1.01-1.39) increase in incident diabetes. SUMMARY: Statins effectively lower atherogenic lipoproteins and result in clinically significant reductions in cardiovascular morbidity and mortality. When well tolerated, the cardiovascular benefits of statins for primary prevention generally far outweigh the reported harms.

Landmark lipid-lowering trials in the primary prevention of cardiovascular disease.

Although atherosclerotic cardiovascular disease (CVD) is the most common cause of morbidity and mortality in the world, the long disease latency affords ample opportunity for preventive care. Indeed, lifelong exposure to atherogenic apoliprotein B-containing lipoproteins has consistently been shown to increase the cumulative risk of suffering a CVD event, including myocardial infarction, stroke, and symptomatic peripheral arterial disease. Over the past 25 years, lipid-lowering therapies have been developed that are proven to not only lower cholesterol, but also to decrease adverse CVD events and CVD mortality. This review will highlight several key clinical trials encompassing several classes of lipid-lowering medications that have provided clinicians with an evidence-based framework for managing their patients' cardiovascular risk.

Impact of fitness versus obesity on routinely measured cardiometabolic risk in young, healthy adults.

Obesity demonstrates a direct relation with cardiovascular risk and all-cause mortality, while cardiorespiratory fitness demonstrates an inverse relation. In clinical practice, several cardiometabolic (CM) risk factors are commonly measured to gauge cardiovascular risk, but the interaction between fitness and obesity with regard to CM risk has not been fully explored. In this study, 2,634 Brazilian adults referred for employer-sponsored heath exams were assessed. Obesity was defined as body mass index >30 kg/m(2) or waist circumference >102 cm in men or >88 cm in women when body mass index was 25 to 30 kg/m(2). Fitness was quantified by stage achieved on an Ellestad treadmill stress test, with those completing stage 4 considered fit. Hepatic steatosis was determined by ultrasound. CM risk factors were compared after stratifying patients into 4 groups: fit and normal weight, fit and obese, unfit and normal weight, and unfit and obese. Approximately 22% of patients were obese; 12% were unfit. Fitness and obesity were moderately correlated (ρ = 0.38 to 0.50). The sample included 6.5% unfit and normal-weight subjects and 16% fit and obese subjects. In overweight and obese patients, fitness was negatively associated with CM risk (p <0.01 for all values). In fit patients, increasing body mass index was positively associated with CM risk (p <0.01 for all values). In instances of discordance between fitness and obesity, obesity was the stronger determinant of CM risk. In conclusion, fitness and obesity are independently associated with CM risk. The effects of fitness and obesity are additive, but obesity is more strongly associated with CM risk when fitness and obesity are discordant. These findings underscore the need for weight loss in obese patients and suggest an unmeasured benefit of fitness.

Evidence-based use of statins for primary prevention of cardiovascular disease.

Three-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as statins, are widely available, inexpensive, and represent a potent therapy for treating elevated cholesterol. Current national guidelines put forth by the Adult Treatment Panel III recommend statins as part of a comprehensive primary prevention strategy for patients with elevated low-density lipoprotein cholesterol at increased risk for developing coronary heart disease within 10 years. Lack of a clear-cut mortality benefit in primary prevention has caused some to question the use of statins for patients without known coronary heart disease. On review of the literature, we conclude that current data support only a modest mortality benefit for statin primary prevention when assessed in the short term (<5 years). Of note, statin primary prevention results in a significant decrease in cardiovascular morbidity over the short and long term and a trend toward increased reduction in mortality over the long term. When appraised together, these data provide compelling evidence to support the use of statins for primary prevention in patients with risk factors for developing coronary heart disease over the next 10 years.

Pressure perturbation calorimetry of helical peptides.

Pressure perturbation calorimetry quantifies the temperature dependence of a solute's thermal expansion coefficient, providing information about solute-solvent interactions. We tested the idea that pressure perturbation calorimetry can provide information about solvent-accessible surface area by studying peptides with different secondary structures. The peptides comprised two host-guest series: one predominately an alpha-helix, the other predominately a polyproline II helix. In aqueous buffer, we find a correlation between the amount of secondary structure as assessed by circular dichroism spectropolarimetry and the pressure perturbation calorimetry data. We conclude that pressure perturbation calorimetry can provide information about the exposure of polar and nonpolar surface area. Data acquired in a buffered urea solution, however, are not as easily interpreted.

Crystal structure of the human ATP-dependent splicing and export factor UAP56.

Pre-mRNA splicing requires the function of a number of RNA-dependent ATPases/helicases, yet no three-dimensional structure of any spliceosomal ATPases/helicases is known. The highly conserved DECD-box protein UAP56/Sub2 is an essential splicing factor that is also important for mRNA export. The expected ATPase/helicase activity appears to be essential for the UAP56/Sub2 functions. Here, we show that purified human UAP56 is an active RNA-dependent ATPase, and we also report the crystal structures of UAP56 alone and in complex with ADP, as well as a DECD to DEAD mutant. The structures reveal a unique spatial arrangement of the two conserved helicase domains, and ADP-binding induces significant conformational changes of key residues in the ATP-binding pocket. Our structural analyses suggest a specific protein-RNA displacement model of UAP56/Sub2. The detailed structural information provides important mechanistic insights into the splicing function of UAP56/Sub2. The structures also will be useful for the analysis of other spliceosomal DExD-box ATPases/helicases.