Araoz, Philip A.

Background— Aortic valve calcification (AVC) is the intrinsic mechanism of valvular obstruction leading to aortic stenosis (AS) and is measurable by multidetector computed tomography. The link between sex and AS is controversial and that with AVC is unknown. Methods and Results— We prospectively performed multidetector computed tomography in 665 patients with AS (aortic valve area, 1.05±0.35 cm 2 ; mean gradient, 39±19 mm Hg) to measure AVC and to assess the impact of sex on the AVC–AS severity link in men and women. AS severity was comparable between women and men (peak aortic jet velocity: 4.05±0.99 versus 3.93±0.91 m/s, P =0.11; aortic valve area index: 0.55±0.20 versus 0.56±0.18 cm 2 /m 2 ; P =0.46). Conversely, AVC load was lower in women versus men (1703±1321 versus 2694±1628 arbitrary units; P <0.0001) even after adjustment for their smaller body surface area or aortic annular area (both P <0.0001). Thus, odds of high-AVC load were much greater in men than in women (odds ratio, 5.07; P <0.0001). Although AVC showed good associations with hemodynamic AS severity in men and women (all r >0.67; P <0.0001), for any level of AS severity measured by peak aortic jet velocity or aortic valve area index, AVC load, absolute or indexed, was higher in men versus women (all P ≤0.01). Conclusions— In this large AS population, women incurred similar AS severity than men for lower AVC loads, even after indexing for their smaller body size. Hence, the relationship between valvular calcification process and AS severity differs in women and men, warranting further pathophysiological inquiry. For AS severity diagnostic purposes, interpretation of AVC load should be different in men and in women.

Background— Constrictive pericarditis (CP) is a disabling disease, and usually requires pericardiectomy to relieve heart failure. Reversible CP has been described, but there is no known method to predict the reversibility. Pericardial inflammation may be a marker for reversibility. As a pilot study, we assessed whether cardiac magnetic resonance imaging pericardial late gadolinium enhancement (LGE) and inflammatory biomarkers could predict the reversibility of CP after antiinflammatory therapy. Method and Results— Twenty-nine CP patients received antiinflammatory medications after cardiac magnetic resonance imaging. Fourteen patients had resolution of CP, whereas 15 patients had persistent CP after 13 months of follow-up. Baseline LGE pericardial thickness was greater in the group with reversible CP than in the persistent CP group (4±1 versus 2±1 mm, P =0.001). Qualitative intensity of pericardial LGE was moderate or severe in 93% of the group with reversible CP and in 33% of the persistent CP group ( P =0.002). Cardiac magnetic resonance imaging LGE pericardial thickness ≥3 mm had 86% sensitivity and 80% specificity to predict CP reversibility. The group with reversible CP also had higher baseline C-reactive protein and erythrocyte sedimentation rate than the persistent CP group (59±52 versus 12±14 mg/L, P =0.04 and 49±25 versus 15±16 mm/h, P =0.04, respectively). Antiinflammatory therapy was associated with a reduction in C-reactive protein, erythrocyte sedimentation rate, and pericardial LGE in the group with reversible CP but not in the persistent CP group. Conclusions— Reversible CP was associated with pericardial and systemic inflammation. Antiinflammatory therapy was associated with a reduction in pericardial and systemic inflammation and LGE pericardial thickness, with resolution of CP physiology and symptoms. Further studies in a larger number of patients are needed.

Background— Myocardial late gadolinium enhancement (LGE) on contrast-enhanced magnetic resonance imaging (CE-MRI) of patients with hypertrophic cardiomyopathy (HCM) has been suggested to represent intramyocardial fibrosis and, as such, an adverse prognostic risk factor. We evaluated the characteristics of LGE on CE-MRI and explored whether LGE among patients with HCM was associated with genetic testing, severe symptoms, ventricular arrhythmias, or sudden cardiac death (SCD). Methods and Results— Four hundred twenty-four patients with HCM (age=55±16 years [range 2 to 90], 41% females), without a history of septal ablation/myectomy, underwent CE-MRI (GE 1.5 Tesla). We evaluated the relation between LGE and HCM genes status, severity of symptoms, and the degree of ventricular ectopy on Holter ECG. Subsequent SCD and appropriate implanted cardioverter defibrillator (ICD) therapies were recorded during a mean follow-up of 43±14 months (range 16 to 94). Two hundred thirty-nine patients (56%) had LGE on CE-MRI, ranging from 0.4% to 65% of the left ventricle. Gene-positive patients were more likely to have LGE ( P <0.001). The frequencies of New York Heart Association class ≥3 dyspnea and angina class ≥3 were similar in patients with and without LGE (125 of 239 [52%] versus 94 of 185 [51%] and 24 of 239 [10%] versus 18 of 185 [10%], respectively, P =NS). LGE-positive patients were more likely to have episodes of nonsustained ventricular tachycardia (34 of 126 [27%] versus 8 of 94 [8.5%], P <0.001), had more episodes of nonsustained ventricular tachycardia per patient (4.5±12 versus 1.1±0.3, P =0.04), and had higher frequency of ventricular extrasystoles/24 hours (700±2080 versus 103±460, P =0.003). During follow-up, SCD occurred in 4 patients, and additional 4 patients received appropriate ICD discharges. All 8 patients were LGE positive (event rate of 0.94%/y, P =0.01 versus LGE negative). Two additional heart failure-related deaths were recorded among LGE-positive patients. Univariate associates of SCD or appropriate ICD discharge were positive LGE ( P =0.002) and presence of nonsustained ventricular tachycardia ( P =0.04). The association of LGE with events remained significant after controlling for other risk factors. Conclusions— In patients with HCM, presence of LGE on CE-MRI was common and more prevalent among gene-positive patients. LGE was not associated with severe symptoms. However, LGE was strongly associated with surrogates of arrhythmia and remained a significant associate of subsequent SCD and/or ICD discharge after controlling for other variables. If replicated, LGE may be considered an important risk factor for sudden death in patients with HCM.

Background— Appropriateness criteria for stress imaging have been published to promote the effective use of stress nuclear scintigraphy and stress echocardiography. We sought to evaluate the application of the stress echocardiography appropriateness criteria to patients undergoing stress echocardiography in an academic medical center. Methods and Results— The stress echocardiography criteria were applied to 298 consecutive patients who underwent stress echocardiography. Patients were rated as appropriate, uncertain, inappropriate, or not classifiable. Results were compared with those of a previous analysis in the same patients using the single-photon computed tomography myocardial perfusion imaging (SPECT MPI) criteria. The level of agreement between 2 cardiac nurse abstractors for categorizing appropriateness by the stress echocardiography criteria was good (κ=0.72). Overall, 54% of patients were classified as appropriate, 8% as uncertain, and 19% as inappropriate; 19% were not classifiable. By the SPECT MPI criteria, 64% of patients were classified as appropriate, 9% as uncertain, and 18% as inappropriate; 9% were not classifiable ( P <0.001 compared with stress echocardiography criteria). By the stress echocardiography criteria, 6 clinical situations or indications accounted for more than 90% of the inappropriate tests; most of these involved asymptomatic patients. Conclusions— Applying stress echocardiography appropriateness criteria to a patient population is feasible, although 1 in 5 of our patients was not classifiable. Overall, the stress echocardiography criteria classified patients differently compared with the SPECT MPI criteria. Future refinements of the appropriateness criteria for stress imaging should address gaps in the criteria and disparities between the stress echocardiography and SPECT MPI criteria.

Background— Obesity is associated with coronary artery calcification (CAC), a marker of the presence and extent of subclinical coronary atherosclerosis. Obesity adds incremental information in identifying those at higher risk of coronary heart disease to traditional risk factor assessment. The present study examined associations between obesity measures and progression of CAC in those at higher (≥10%) and lower (<10%) 10-year coronary heart disease risk according to the Framingham risk equation. Methods and Results— In this study, 443 asymptomatic white individuals >30 years of age (243 men) had baseline and follow-up CAC measurements an average of 8.9 years apart. Multivariable linear regression models were fit to determine associations of obesity measures at baseline with progression of CAC defined as log e of the difference between follow-up and baseline CAC area plus 1 divided by time (in years) between examinations, adjusting for baseline CAC quantity, age, sex, baseline hypertension status, and baseline cholesterol level. Among 329 participants (74.3%) in the lower-risk group, waist circumference ( P =0.024), waist-to-hip ratio ( P <0.001), body mass index ( P =0.036), and being overweight compared with being underweight or of normal weight ( P =0.008) were each significantly positively associated with progression of CAC. Among those at higher coronary heart disease risk, no baseline obesity measures were associated with CAC progression. Conclusions— Various measures of obesity were associated with increased progression of CAC in those at lower risk of coronary heart disease. Future studies examining the effectiveness of weight reduction strategies in reducing CAC progression among those with an otherwise favorable risk factor profile may be warranted.