Prognostic Significance of Elevated Left Ventricular Filling Pressures with Exercise: Insights from a Cohort of 14,338 Patients.

BACKGROUND: Exercise echocardiography can assess for cardiovascular causes of dyspnea other than coronary artery disease. However, the prevalence and prognostic significance of elevated left ventricular (LV) filling pressures with exercise is understudied. METHODS: We evaluated 14,338 patients referred for maximal symptom-limited treadmill echocardiography. In addition to assessment of LV regional wall motion abnormalities (RWMAs), we measured patients' early diastolic mitral inflow (E), septal mitral annulus relaxation (e'), and peak tricuspid regurgitation velocity before and immediately after exercise. RESULTS: Over a mean follow-up of 3.3 ± 3.4 years, patients with E/e' ≥15 with exercise (n = 1,323; 9.2%) had lower exercise capacity (7.3 ± 2.1 vs 9.1 ± 2.4 metabolic equivalents, P < .0001) and were more likely to have resting or inducible RWMAs (38% vs 18%, P < .0001). Approximately 6% (n = 837) had elevated LV filling pressures without RWMAs. Patients with a poststress E/e' ≥15 had a 2.71-fold increased mortality rate (2.28-3.21, P < .0001) compared with those with poststress E/e' ≤ 8. Those with an E/e' of 9 to 14, while at lower risk than the E/e' ≥15 cohort (hazard ratio [HR] = 0.58 [0.48-0.69]; P < .0001), had higher risk than if E/e' ≤8 (HR = 1.56 [1.37-1.78], P < .0001). On multivariable analysis, adjusting for age, sex, exercise capacity, LV ejection fraction, and presence of pulmonary hypertension with stress, patients with E/e' ≥15 had a 1.39-fold (95% CI, 1.18-1.65, P < .0001) increased risk of all-cause mortality compared with patients without elevated LV filling pressures. Compared with patients with E/e' ≤ 15 after exercise, patients with E/e' ≤15 at rest but elevated after exercise had a higher risk of cardiovascular death (HR = 8.99 [4.7-17.3], P < .0001). CONCLUSION: Patients with elevated LV filling pressures are at increased risk of death, irrespective of myocardial ischemia or LV systolic dysfunction. These findings support the routine incorporation of LV filling pressure assessment, both before and immediately following stress, into the evaluation of patients referred for exercise echocardiography.

Raphal Cord Rupture: A Rare Mechanism of Aortic Regurgitation in Bicuspid Aortic Valve.

A 70-year-old male with chronic aortic regurgitation was referred with abrupt worsening heart failure. Late referral markers were pulmonary hypertension, mitral regurgitation, and tricuspid regurgitation. Evaluation revealed rupture of a raphal cord or fenestrated raphe from the conjoined cusp of a congenitally bicuspid aortic valve, a rare mechanism of aortic regurgitation. (Level of Difficulty: Intermediate.).

Performance of cardiac PET/CT with and without phase analysis for detection of scar in cardiac sarcoidosis: Comparison to cardiac magnetic resonance imaging.

BACKGROUND: The presence of myocardial scar in CS patients results in poor prognosis and worse outcomes. 18F-fluorodeoxyglucose (18F-FDG) PET/CT excels at visualizing inflammation but is suboptimal at detecting scar. We evaluated PET/CT sensitivity to detect scar and investigated the incremental diagnostic value of automated PET-derived data. METHODS: 176 patients who underwent cardiac magnetic resonance (CMR) and N-13 ammonia/18F-FDG cardiac PET/CT for suspected CS within 3 months were enrolled. Scar was defined as late gadolinium enhancement (LGE) on CMR without concordant 18F-FDG uptake on 18F-FDG PET/CT. Accuracy of cardiac PET/CT at detecting scar (perfusion defect without concordant 18F-FDG uptake) was assessed before and after addition of automated PET-derived data. RESULTS: Sensitivity of PET/CT for scar detection was 45.3% (specificity 88.9%). Addition of PET-derived LV volumes and function in a logistic regression model improved sensitivity to 57.0% (specificity: 80.0%, AUC 0.72). Addition of phase analysis maximum segmental onset of myocardial contraction > 61 improved AUC to 0.75, correctly relabeling 16.3% of patients as scar (net reclassification index 8.2%). CONCLUSION: Sensitivity of gated PET MPI alone for scar detection in CS is suboptimal. Adding PET-derived volumes/function and phase analysis data results in improved detection and characterization of scar.

Impact of Anemia on Exercise and Pharmacologic Stress Echocardiography.

BACKGROUND: The safety and diagnostic accuracy of stress testing in anemic patients have not been well studied. Despite a lack of data, significant anemia may be considered a relative contraindication to stress testing because of safety concerns related to insufficient myocardial oxygen supply. METHODS: The authors reviewed 28,829 consecutive patients with blood hemoglobin drawn within 48 hours of stress echocardiography (15,624 exercise and 13,205 dobutamine). The associations of blood hemoglobin concentration with arrhythmia and other stress echocardiographic findings were examined. Additionally, the effect of anemia on the positive predictive value of stress echocardiography for the detection of significant coronary artery stenosis (≥50%) was assessed in patients who subsequently underwent coronary angiography. RESULTS: Anemia was present in 6,401 patients (22.2%) and was severe (hemoglobin < 8.0 g/dL) in 52. Stress testing with either exercise or dobutamine was safe, with no significant increase in serious arrhythmia events or need for hospitalization. In the exercise cohort, worsening anemia was associated with reduced treadmill exercise time, lower peak heart rate, peak rate-pressure product, and achieved workload. In the dobutamine stress cohort, worsening anemia was associated with higher resting heart rate, more use of atropine, and fewer patients attaining target heart rate. The positive predictive value of stress echocardiography was higher in patients with moderate anemia compared with those without anemia (71.8% vs 60.2%, P = .01). CONCLUSIONS: This study demonstrates that stress testing is safe in patients with mild and moderately anemia, albeit with a small increase in mild supraventricular arrhythmias with exercise. However, worsening anemia was associated with a significant reduction in exercise capacity. Additionally, worsening anemia was associated with an improvement in the positive predictive value of stress echocardiography. Extrapolation of these data to patients with severe anemia should be performed with caution given the limited number of patients with severe anemia in this study.

Dobutamine Stress Echocardiography: Impact of Abnormal Blood Potassium Levels on Cardiac Arrhythmias.

BACKGROUND: Guidelines suggest that an abnormal blood potassium level is a relative contraindication to performing dobutamine stress echocardiography (DSE). However, this has not been previously studied. METHODS: We reviewed a consecutive series of patients who had potassium testing within 48 hours of undergoing DSE for the evaluation of myocardial ischemia over a 10-year period (N = 13,198). Normal potassium range in our laboratory is 3.6-5.2 mmol/L. Hemolyzed samples were not included. The association of potassium levels with the development of supraventricular and ventricular arrhythmias was assessed. RESULTS: The incidence of clinically significant arrhythmias was very low (supraventricular tachycardia/atrial fibrillation, 4.9%; nonsustained ventricular tachycardia, 2.9%; sustained ventricular tachycardia or ventricular fibrillation, 0.1%), confirming the overall safety of DSE. Most arrhythmias (88%) occurred in patients with normal potassium levels, and arrhythmia rates remained low in patients with potassium abnormalities. Patients with hyperkalemia had a lower risk of developing mild (odds ratio [OR], 0.39; 95% CI, 0.22-0.71) and severe (OR, 0.13; 95% CI, 0.01-0.68) supraventricular arrhythmias as well as mild ventricular arrhythmias (OR, 0.58; 95% CI, 0.40-0.83). Even though events were rare, patients with severe hypokalemia (potassium levels ≤ 3.1 mmol/L) had an increased risk of supraventricular arrhythmia and ventricular ectopy. CONCLUSIONS: DSE is safe even in the setting of abnormalities in blood potassium concentrations, and hence cancellation of DSE in patients with potassium abnormalities does not appear warranted. Elevated potassium levels are associated with lower rates of clinically significant supraventricular and ventricular arrhythmias. While remaining at relatively low risk, patients with very low potassium levels (≤3.1 mmol/L) at the time of DSE have a modestly increased risk of arrhythmia. Consideration could be given to correcting severe hypokalemia prior to DSE.

Glucocorticoid regulation of amino acid and polyamine metabolism in the small intestine.

Several factors (including diets, changes in intestinal fluora, and hormones) regulate postnatal intestinal growth and development. Based on the early studies involving modification of the adrenal gland, pituitary gland or hypothalamus, exogenous glucocorticoids and glucocorticoid receptor antagonists are now used to study glucocorticoid-mediated metabolism of amino acids in the small intestine. Findings from these studies indicate that physiological levels of glucocorticoids stimulate the catabolism of glutamine and proline for the synthesis of citrulline and arginine in enterocytes during weaning. In addition, increases in circulating levels of glucocorticoids enhance expression of arginase, proline oxidase and ornithine decarboxylase, as well as polyamine synthesis from arginine and proline in enterocytes. These actions of the hormones promote intestinal maturation and may have therapeutic effects on intestinal disease (e.g., necrotizing enterocolitis). Molecular aspects, species-specific effects, and developmental responsiveness to glucocorticoids should be taken into consideration in designing both experimental and clinical studies.