Barnes, Marion E.

Background: Left atrial (LA) size increases in atrial fibrillation (AF). How changes in mitral annulus and atrial volume over time relate to severity of mitral regurgitation (MR) is unknown. Methods: This cohort study included 160 patients with a history of permanent AF who had at least 2 transthoracic echocardiograms (TTE) performed between 2005 and 2010 at Vancouver General Hospital (British Columbia, Canada). Patients with structural mitral valve disease, congenital heart disease, more than mild-moderate mitral/tricuspid regurgitation on their first TTE were excluded from analyses. LA volume was determined using biplane area-length method, averaged over 3 cardiac cycles. The mitral annulus diameter (MAD), defined as the distance between the hinge points of the anterior and posterior mitral leaflets from the apical 4-chamber view, was measured during end-systole and end-diastole. Linear mixed effects modeling was used in analyzing the above measurements for change over time. Mitral regurgitation was classified into 3 grades (mild, moderate, or severe) using standard color Doppler and PISA easurements where available. Results: Of the 160 subjects included in this analysis, 100 were men (62.5%). The mean age at study entry was 74±10 years. The median number of TTE performed was 3 (range 2 - 6). All 160 patients showed a progressive increase in MAD over time. There was a significant increase in MAD at end-systole and end-diastole over a mean follow-up of 3.2 ± 2.8 years; the increases were 0.48 mm/year (95% CI 0.124 -0.75, P=0.0037) and 0.45 mm/year (95% CI 0.102-0.716, P=0.0029) respectively. LA volume increased from a mean of 43 mL/m2 to 75 mL/m2 for the cohort, or 10 mL/m2 per year. Adjusting for age, sex, and left ventricular ejection fraction, an increase in MR severity by at least 1 grade was strongly and independently associated with an increase in MAD. A 15% increment in MAD was associated with an increase in MR severity by 1 grade. Conclusion: Permanent AF was associated with significant increases in MAD and LA volume over time. Severity of MR also significantly increased over time, and was independently related to the change in MAD. Further investigations as to whether this represents a mechanism for left heart failure in patients with permanent AF are warranted.

Background: Assessment of coexisting pericardial and myocardial disease in constrictive pericarditis (CP) remains a diagnostic challenge and decision for pericardiectomy depends on the degree of pericardial versus myocardial restraint limiting left ventricular (LV) filling. Early diastolic longitudinal mitral annulus velocity (Ea) can help to differentiate CP from restrictive cardiomyopathy. Recently, acceleration rate of Ea has been shown to be an index of LV myocardial relaxation. We therefore assessed acceleration (Ea-AR) and deceleration (Ea-DR) rate of Ea in patients with CP before and after pericardiectomy. Methods: We retrospectively studied patients (n=42) with surgically confirmed CP who underwent radical pericardiectomy between 2003–2006 at Mayo Clinic Rochester. Ea-AR and Ea-DR slopes were measured before (pre-Echo) and after (post-Echo) pericardiectomy. Patients were divided into primary CP (idiopathic & acute pericarditis with presumed normal myocardial function) and secondary CP (cardiac surgery & chest irradiation with presumed abnormal myocardial function). Results: Ea-AR and Ea-DR changed significantly after pericardiectomy in primary CP patients, however remained similar in secondary CP patients. Diagnostic accuracy of Ea-AR, Ea-DR and Ea to discriminate primary versus secondary CP by ROC analysis was 0.88, 0.80 and 0.81 respectively. Conclusion: Assessment of Ea-AR and Ea-DR in patients with CP is useful to discriminate primary from secondary CP and may help to predict coexistence of myocardial disease: Prepericardiectomy Ea-AR and Ea-DR appear to reflect the interaction of intrinsic myocardial relaxation with enhanced early LV filling. The lack of decrease of Ea-AR and Ea-DR in patients with secondary CP seems to indicate a primarily restrictive component. The significant decrease of Ea-DR in patients with primary CP after pericardiectomy could reflect abolition of a predominant pericardial limitation to LV filling. Early Diastolic Longitudinal Mitral Annulus Motion before and after Pericardiectomy

Abstract Background: Clinical observations within our tertiary care setting suggested that atrial arrhythmia is common following hematopoietic stem-cell transplant (SCT). Yet little is known with regard to the incidence of such arrhythmia and factors contributing to its development. We assessed the frequency of first atrial fibrillation/flutter (AF/flutter) development in multiple myeloma (MM) patients who underwent SCT at the Mayo Clinic over a 4 year period. Method: Using a case-control design, we compared 395 consecutive patients who underwent SCT at the Mayo Clinic during the period 2002–2005 to control subjects who did not have SCT (2:1 matched by age, gender, and date of MM diagnosis) in terms of the baseline risk factors and the frequency of new AF/flutter after MM diagnosis. Patients who had a prior history or evidence of atrial arrhythmia were excluded from analyses. Factors predictive of atrial arrhythmia in the cases were also determined. Results: First AF/Flutter developed in 38 of 395 cases (mean age 58 ± 9 years) and 47 of 790 controls subjects within 5 years of MM diagnosis (P=0.002). The 5-year Kaplan-Meier estimates of the risk of AF/flutter were 17% and 8% for cases and controls, respectively. Amongst the cases who developed new AF/flutter, the onset of the arrhythmia was within 21 days of SCT for the majority (94%). In multivariable analysis, body weight change of ≥3% in the first week post-transplant (HR 2.86; CI 1.13–7.24; P=0.026) and presence of diastolic dysfunction (HR 1.79; CI 0.99–3.23; p=0.054) at MM diagnosis were independent predictors of first AF/flutter in the cases, adjusting for age, sex, and well established clinical risk factors. Conclusion: The risk for new AF/flutter was remarkably high in the early post- SCT period in MM patients. In addition to established risk factors for atrial arrhythmia, a weight change ≥3% during the first 7 days after SCT, and the presence of diastolic dysfunction at baseline, were independent novel risk factors for new AF/flutter. These findings warrant further investigation, as modification of fluid management and diastolic filling may potentially lower the risk of post-SCT atrial arrhythmia.

Background: Although a gradual increase in heart rate (HR) during dobutamine stress testing (DST) is desired, few data exists regarding whether this is similarly achieved in patients of widely varying body mass index (BMI). Whether difference in BMI contributes to variation in the hemodynamic and symptomatic response to dobutamine is also unknown. Methods: From prospectively acquired data of 2776 consecutive patients who underwent DST according to standard weight-based clinical protocol, we classified patients into 4 groups of BMI (kg/m 2 ): <25 (normal), 25 to 29.9 (overweight), 30 to 39.9 (obese), and ≥40 (severely obese) and compared the rate of increase of HR, mean blood pressure, and development of symptoms for the groups. Results: Age was 68 + 12 years, 52% were men, BMI was 29.8 + 6.6 kg/m 2 (range 14.5-81.4), 198 (7%) had BMI ≥40, and target HR was achieved in 2433 (88%). The rate of increase in HR was similar for each group of BMI after adjustment for age, gender, baseline HR, negative chronotropic use, and atropine administration. The percentage of patients in each group who achieved target HR was similar and the percentage of target HR achieved at each stage of dobutamine was essentially equivalent. Blood pressure responses and development of symptoms were similar in the 4 groups of BMI. Independent predictors of failure to achieve target HR included age, diabetes mellitus, treatment with negative chronotropic medications, and baseline HR; BMI was not a predictor (odds ratio [OR] 0.98, P = .086). Conclusion: The current weight-based protocol of dobutamine dosing for DST results in similar increases in HR and blood pressure for patients of widely varying BMI.

Background— Limited data exist on trends in incidence of atrial fibrillation (AF). We assessed the community-based trends in AF incidence for 1980 to 2000 and provided prevalence projections to 2050. Methods and Results— The adult residents of Olmsted County, Minnesota, who had ECG-confirmed first AF in the period 1980 to 2000 (n=4618) were identified. Trends in age-adjusted incidence were determined and used to construct model-based prevalence estimates. The age- and sex-adjusted incidence of AF per 1000 person-years was 3.04 (95% CI, 2.78 to 3.31) in 1980 and 3.68 (95% CI, 3.42 to 3.95) in 2000. According to Poisson regression with adjustment for age and sex, incidence of AF increased significantly ( P =0.014), with a relative increase of 12.6% (95% CI, 2.1 to 23.1) over 21 years. The increase in age-adjusted AF incidence did not differ between men and women ( P =0.84). According to the US population projections by the US Census Bureau, the number of persons with AF is projected to be 12.1 million by 2050, assuming no further increase in age-adjusted incidence of AF, but 15.9 million if the increase in incidence continues. Conclusions— The age-adjusted incidence of AF increased significantly in Olmsted County during 1980 to 2000. Whether or not this rate of increase continues, the projected number of persons with AF for the United States will exceed 10 million by 2050, underscoring the urgent need for primary prevention strategies against AF development.

Background and Purpose— With the changes in management of atrial fibrillation (AF) over time, it is possible that the time trends of post-AF stroke incidence and mortality have changed. We sought to determine whether the incidence and survival of ischemic stroke after AF diagnosis have improved. Methods— We identified the Olmsted County, Minn, residents who developed first AF from 1980 to 2000 and followed them in medical records to 2004. The outcomes were first ischemic stroke and death. Results— Of the 4117 subjects diagnosed with first AF and without previous stroke, 446 (11%) sustained a first ischemic stroke during a mean follow-up time of 5.5±5.0 years. The age- and sex-adjusted incidence of stroke decreased, on average, by 3.4% per year ( P =0.0001), concurrent with an increase in warfarin and aspirin use (both P <0.0001) and reduction of systolic blood pressure ( P <0.001). The age-adjusted ischemic stroke incidence was higher in women ( P =0.039), but not after adjusting for systolic blood pressure ( P =0.41). Compared with the general Minnesota white population, the relative mortality hazard ratio was 1.88 for men and 1.84 for women without stroke and 3.03 for men and 3.80 for women ( P <0.05) with stroke. The relative mortality hazard did not vary by age or calendar year of AF diagnosis. Conclusions— Post-AF ischemic stroke incidence decreased significantly from 1980 to 2000, during which time a substantial increase in the use of antithrombotic therapy and reduction of systolic blood pressure was evident. The relative mortality risk of stroke, however, had not improved over time.

Background— This study assessed the long-term outcome of a large, asymptomatic population with hemodynamically significant aortic stenosis (AS). Methods and Results— We identified 622 patients with isolated, asymptomatic AS and peak systolic velocity ≥4 m/s by Doppler echocardiography who did not undergo surgery at the initial evaluation and obtained follow-up (5.4±4.0 years) in all. Mean age (±SD) was 72±11 years; there were 384 (62%) men. The probability of remaining free of cardiac symptoms while unoperated was 82%, 67%, and 33% at 1, 2, and 5 years, respectively. Aortic valve area and left ventricular hypertrophy predicted symptom development. During follow-up, 352 (57%) patients were referred for aortic valve surgery and 265 (43%) patients died, including cardiac death in 117 (19%). The 1-, 2-, and 5-year probabilities of remaining free of surgery or cardiac death were 80%, 63%, and 25%, respectively. Multivariate predictors of all-cause mortality were age (hazard ratio [HR], 1.05; P <0.0001), chronic renal failure (HR, 2.41; P =0.004), inactivity (HR, 2.00; P =0.001), and aortic valve velocity (HR, 1.46; P =0.03). Sudden death without preceding symptoms occurred in 11 (4.1%) of 270 unoperated patients. Patients with peak velocity ≥4.5 m/s had a higher likelihood of developing symptoms (relative risk, 1.34) or having surgery or cardiac death (relative risk, 1.48). Conclusions— Most patients with asymptomatic, hemodynamically significant AS will develop symptoms within 5 years. Sudden death occurs in ≈1%/y. Age, chronic renal failure, inactivity, and aortic valve velocity are independently predictive of all-cause mortality.