Barry L. Karon

Progression of Left Ventricular Diastolic Dysfunction and Risk of Heart Failure

CONTEXT Heart failure incidence increases with advancing age, and approximately half of patients with heart failure have preserved left ventricular ejection fraction. Although diastolic dysfunction plays a role in heart failure with preserved ejection fraction, little is known about age-dependent longitudinal changes in diastolic function in community populations. OBJECTIVE To measure changes in diastolic function over time and to determine the relationship between diastolic dysfunction and the risk of subsequent heart failure. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort of participants enrolled in the Olmsted County Heart Function Study. Randomly selected participants 45 years or older (N = 2042) underwent clinical evaluation, medical record abstraction, and echocardiography (examination 1 [1997-2000]). Diastolic left ventricular function was graded as normal, mild, moderate, or severe by validated Doppler techniques. After 4 years, participants were invited to return for examination 2 (2001-2004). The cohort of participants returning for examination 2 (n = 1402 of 1960 surviving [72%]) then underwent follow-up for ascertainment of new-onset heart failure (2004-2010). MAIN OUTCOME MEASURES Change in diastolic function grade and incident heart failure. RESULTS During the 4 (SD, 0.3) years between examinations 1 and 2, diastolic dysfunction prevalence increased from 23.8% (95% confidence interval [CI], 21.2%-26.4%) to 39.2% (95% CI, 36.3%-42.2%) (P < .001). Diastolic function grade worsened in 23.4% (95% CI, 20.9%-26.0%) of participants, was unchanged in 67.8% (95% CI, 64.8%-70.6%), and improved in 8.8% (95% CI, 7.1%-10.5%). Worsened diastolic dysfunction was associated with age 65 years or older (odds ratio, 2.85 [95% CI, 1.77-4.72]). During 6.3 (SD, 2.3) years of additional follow-up, heart failure occurred in 2.6% (95% CI, 1.4%-3.8%), 7.8% (95% CI, 5.8%-13.0%), and 12.2% (95% CI, 8.5%-18.4%) of persons whose diastolic function normalized or remained normal, remained or progressed to mild dysfunction, or remained or progressed to moderate or severe dysfunction, respectively (P < .001). Diastolic dysfunction was associated with incident heart failure after adjustment for age, hypertension, diabetes, and coronary artery disease (hazard ratio, 1.81 [95% CI, 1.01-3.48]). CONCLUSIONS In a population-based cohort undergoing 4 years of follow-up, prevalence of diastolic dysfunction increased. Diastolic dysfunction was associated with development of heart failure during 6 years of subsequent follow-up.

Outcome after normal exercise echocardiography and predictors of subsequent cardiac events : Follow-up of 1,325 patients

OBJECTIVES This study sought to examine the outcome of a large group of patients after normal exercise echocardiography and to identify potential predictors of subsequent cardiac events. BACKGROUND Earlier studies suggested that prognosis after normal exercise echocardiography is favorable, with a low subsequent cardiac event rate. These studies involved a small number of patients and did not have sufficient statistical power to stratify risk. METHODS The outcomes of 1,325 patients who had normal exercise echocardiograms were examined. End points were overall and cardiac event-free survival. Cardiac events were defined as cardiac death, nonfatal myocardial infarction and coronary revascularization. Patient characteristics were analyzed in relation to time to first cardiac event in a univariate and multivariate manner to determine which, if any, were associated with an increased hazard of subsequent cardiac events. RESULTS Overall survival of the study group was significantly better than that of an age- and gender-matched group obtained from life tables (p < 0.0001). The cardiac event-free survival rates at 1, 2 and 3 years were 99.2%, 97.8% and 97.4%, respectively. The cardiac event rate per person-year of follow-up was 0.9%. Subgroups with an intermediate or high pretest probability of having coronary artery disease also had low cardiac event rates. Multivariate predictors of subsequent cardiac events were angina during treadmill exercise testing (risk ratio [RR] 4.1, 95% confidence interval [CI] 1.5 to 11.0), low work load (defined as < 7 metabolic equivalents [METs] for men and < 5 METs for women; RR 3.2, 95% CI 1.4 to 7.6), echocardiographic left ventricular hypertrophy (RR 2.6, 95% CI 1.1 to 6.3) and advancing age (RR 1.04/year, 95% CI 1.0 to 1.1). CONCLUSIONS The outcome after normal exercise echocardiography is excellent. Subgroups with an intermediate or high pretest probability of having coronary artery disease also have a favorable prognosis after a normal exercise echocardiogram. Characteristics predictive of subsequent cardiac events (i.e., patient age, work load, angina during exercise testing and echocardiographic left ventricular hypertrophy) should be considered in the clinical interpretation of a normal exercise echocardiogram.

Increased prevalence of diastolic dysfunction in rheumatoid arthritis

Objective To compare the prevalence of left ventricular (LV) diastolic dysfunction in subjects with and without rheumatoid arthritis (RA), among those with no history of heart failure (HF), and to determine risk factors for diastolic dysfunction in RA. Methods A cross-sectional, community-based study comparing cohorts of adults with and without RA and without a history of HF was carried out. Standard two-dimensional/Doppler echocardiography was performed in all participants. Diastolic dysfunction was defined as impaired relaxation (with or without increased filling pressures) or advanced reduction in compliance or reversible or fixed restrictive filling. Results The study included 244 subjects with RA and 1448 non-RA subjects. Mean age was 60.5 years in the RA cohort (71% female) and 64.9 years (50% female) in the non-RA cohort. The vast majority (>98%) of both cohorts had preserved ejection fraction (EF≥50%). Diastolic dysfunction was more common in subjects with RA at 31% compared with 26% (age and sex adjusted) in non-RA subjects (OR=1.6; 95% CI 1.2 to 2.4). Patients with RA had significantly lower LV mass, higher pulmonary arterial pressure and higher left atrial volume index than non-RA subjects. RA duration and interleukin 6 (IL-6) level were independently associated with diastolic dysfunction in RA even after adjustment for cardiovascular risk factors. Conclusion Subjects with RA have a higher prevalence of diastolic dysfunction than those without RA. RA duration and IL-6 are independently associated with diastolic dysfunction, suggesting the impact of chronic autoimmune inflammation on myocardial function in RA. Clinical implications of these findings require further investigation.

Longitudinal Changes in Left Ventricular Stiffness A Community-Based Study

Background—Cross-sectional studies suggest that left ventricular (LV) and arterial elastance (stiffness) increase with age, but data examining longitudinal changes within human subjects are lacking. In addition, it remains unknown whether age-related LV stiffening is merely a reaction to arterial stiffening or caused by other processes. Methods and Results—Comprehensive echo-Doppler cardiography was performed in 1402 subjects participating in a randomly selected community-based study at 2 examinations separated by 4 years. From this population, 788 subjects had adequate paired data to determine LV end-systolic elastance (Ees), end-diastolic elastance (Eed), and effective arterial elastance. Throughout 4 years, blood pressure, arterial elastance, and LV mass decreased, coupled with significantly greater use of antihypertensive medications. However, despite reductions in arterial load, Ees increased by 14% (2.10±0.67–2.26±0.70 mm Hg/mL; P<0.0001) and Eed increased by 8% (0.13±0.03–0.14±0.04 mm Hg/mL; P<0.0001). Increases in Eed were greater in women than men, whereas Ees changes were similar. Age-related increases in Ees and Eed were correlated with changes in body weight, but were similar in subjects with or without cardiovascular disease. Changes in Ees were correlated with Eed (r=0.5; P<0.0001), but not with other measures of contractility, indicating that the increase in Ees was reflective of passive stiffening rather than enhanced systolic function. Conclusions—Despite reductions in arterial load with medical therapy, LV systolic and diastolic stiffness increase over time in humans, particularly in women. In addition to blood pressure control, therapies targeting load-independent ventricular stiffening may be effective to treat and prevent age-associated cardiovascular diseases, such as heart failure.

Longitudinal Changes in Left Ventricular StiffnessClinical Perspective

Background—Cross-sectional studies suggest that left ventricular (LV) and arterial elastance (stiffness) increase with age, but data examining longitudinal changes within human subjects are lacking. In addition, it remains unknown whether age-related LV stiffening is merely a reaction to arterial stiffening or caused by other processes. Methods and Results—Comprehensive echo-Doppler cardiography was performed in 1402 subjects participating in a randomly selected community-based study at 2 examinations separated by 4 years. From this population, 788 subjects had adequate paired data to determine LV end-systolic elastance (Ees), end-diastolic elastance (Eed), and effective arterial elastance. Throughout 4 years, blood pressure, arterial elastance, and LV mass decreased, coupled with significantly greater use of antihypertensive medications. However, despite reductions in arterial load, Ees increased by 14% (2.10±0.67–2.26±0.70 mm Hg/mL; P<0.0001) and Eed increased by 8% (0.13±0.03–0.14±0.04 mm Hg/mL; P<0.0001). Increases in Eed were greater in women than men, whereas Ees changes were similar. Age-related increases in Ees and Eed were correlated with changes in body weight, but were similar in subjects with or without cardiovascular disease. Changes in Ees were correlated with Eed (r=0.5; P<0.0001), but not with other measures of contractility, indicating that the increase in Ees was reflective of passive stiffening rather than enhanced systolic function. Conclusions—Despite reductions in arterial load with medical therapy, LV systolic and diastolic stiffness increase over time in humans, particularly in women. In addition to blood pressure control, therapies targeting load-independent ventricular stiffening may be effective to treat and prevent age-associated cardiovascular diseases, such as heart failure.

Prostate brachytherapy seed migration to a coronary artery found during angiography

Vascular migration of radioactive seeds to the lungs following permanent prostate brachytherapy is a recognized phenomenon. We report a case in which a seed became lodged in a coronary artery. CASE REPORT A 77-year-old man with a long-standing history of coronary artery disease underwent transperineal interstitial permanent prostate brachytherapy elsewhere in mid 2000 for treatment of early stage prostate cancer. More than 80 103 palladium loose radioactive seeds (TheraSeed Model 200, Theragenics Corp., Buford, Georgia) were implanted in the prostate and periprostatic tissues. Nine months after brachytherapy, the patient experienced increasing intermittent chest pain and underwent coronary angiography at our institution. This study demonstrated multiple vessel coronary artery disease and the presence of a metallic object in the septal perforator branch of the left anterior descending coronary artery. X-ray of the pelvis revealed the presence of multiple brachytherapy seeds in the prostate with radiopaque markers of the same size (approximately 1.1 mm. 0.5 mm.) as that of the metallic object in the coronary artery. Symptoms were deemed unrelated to the presence of the brachytherapy seed in the coronary artery according to the attending cardiologists (J. F. B., B. L. K.). Examination of the cine angiogram and pelvic x-ray by all coauthors confirmed that the metallic object in the coronary artery was a brachytherapy seed that had migrated (see figure). DISCUSSION We report a case of radioactive seed migration to a coronary artery. We previously described a case of seed migration to the right ventricle and noted that the presence of a right to left cardiac shunt might allow seed migration to a coronary artery or other locations.1 Seeds used in transperineal interstitial permanent prostate brachytherapy are 4.5 mm. in length and 800 m. in diameter and, thus, are small enough to migrate through the venous system to the right ventricle and become lodged in small pulmonary arterioles.2, 3 It is noteworthy that 25% of adults are found to have a probe patent foramen ovale at autopsy and, therefore, may have a right to left shunt. Such shunts are usually clinically insignificant, but they could nevertheless allow passage of a brachytherapy seed from the right to the left ventricle and into a coronary artery without traversing the pulmonary vasculature. Prior reports indicate that the percentage of patients who have at least 1 seed migrate to the chest following transperineal interstitial permanent prostate brachytherapy varies widely from 0.7% to 55%, whereas the total percentage of seeds that eventually migrate is less than 1%.2, 3 Thus, seed

Brief report: rheumatoid arthritis is associated with left ventricular concentric remodeling: results of a population-based cross-sectional study.

OBJECTIVE To study left ventricular (LV) geometry in patients with rheumatoid arthritis (RA) and no history of heart failure compared with that in subjects with neither RA nor a history of heart failure, and to determine the impact of RA on LV remodeling. METHODS A cross-sectional, community-based study was conducted among adult (age ≥50 years) patients with RA and age- and sex-matched subjects with neither RA nor a history of heart failure. All participants underwent standard 2-dimensional Doppler echocardiography. LV geometry was classified into the following 4 categories based on relative wall thickness and sex-specific cutoffs for the LV mass index: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, or normal geometry. RESULTS Among 200 patients with RA and 600 age- and sex-matched subjects without RA, the mean age was 65 years, and 74% of the individuals in both cohorts were female. Compared with subjects without RA, patients with RA were significantly more likely to have abnormal LV geometry (odds ratio [OR] 1.44, 95% confidence interval [95% CI] 1.03-2.00), even after adjusting for cardiovascular risk factors and comorbidities. Among subjects with abnormal LV geometry, the odds of concentric LV remodeling were significantly increased in patients with RA (OR 4.73, 95% CI 2.85-7.83). In linear regression analyses, the LV mass index appeared to be lower in patients with RA who were currently receiving corticosteroids (β ± SE -0.082 ± 0.027, P = 0.002), even after adjusting for cardiovascular risk factors and comorbidities. CONCLUSION RA was strongly associated with abnormal LV remodeling (particularly concentric LV remodeling) among RA patients without heart failure. This association remained significant after adjustment for cardiovascular risk factors and comorbidities. RA disease-related factors may promote changes in LV geometry. The biologic mechanisms underlying LV remodeling warrant further investigation.

Application of the Appropriateness Criteria for Echocardiography in an Academic Medical Center

BACKGROUND The authors examined the feasibility of application of the American College of Cardiology Foundations appropriateness criteria for transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) at a large tertiary care practice. METHODS Indications for consecutive TTE and TEE were determined by chart review and classified according to the guidelines as appropriate, inappropriate, or uncertain or, for situations not addressed in the document, nonclassifiable. RESULTS Of the 529 studies reviewed, 469 were appropriate, 23 inappropriate, 1 uncertain, and 36 nonclassifiable. Inappropriate and nonclassifiable studies were more commonly TTE than TEE (P<.001). Inappropriate studies were more common in outpatients than inpatients (P<.001). Nonclassifiable cases included assessment after radiofrequency ablation (33.3%) and preoperative evaluation (8.3%). Disagreement between observers in selection of the criterion was present in 30.8%. CONCLUSIONS Although the study was conducted retrospectively, only 4.7% of classifiable studies were inappropriate. The reproducibility of classification was moderate, and 6.8% of studies were not classifiable. Areas for improvement of the criteria were identified.

Strain Dyssynchrony Index Correlates With Improvement in Left Ventricular Volume After Cardiac Resynchronization Therapy Better Than Tissue Velocity Dyssynchrony Indexes

Background—Various dyssynchrony indexes derived from tissue velocity and strain imaging have been proposed to predict the effectiveness of cardiac resynchronization therapy (CRT). We sought to compare the effect of CRT on dyssynchrony indexes derived by tissue velocity and strain and to determine which baseline intraventricular dyssynchrony parameters correlate with improvement in left ventricular volume after CRT. Methods and Results—Echocardiography with tissue Doppler imaging was performed in 45 patients with systolic heart failure at baseline, 1 day after CRT, and a median of 6 months after CRT. We calculated septal–lateral delay and anteroseptal–posterior delay and standard deviation of time to peak systolic velocity in the 12 basal and mid-left ventricular segments (Tv-SD). The standard deviation for time to peak strain in the 12 basal and mid-left ventricular segments (Tϵ-SD) was calculated as a strain-derived dyssynchrony index. None of the tissue velocity–derived dyssynchrony indexes improved after CRT (septal–lateral delay, P=0.39; anteroseptal–posterior delay, P=0.46; Tv-SD, P=0.30), whereas Tϵ-SD decreased significantly after CRT (P<0.001). Improvement in Tϵ-SD 1 day after CRT correlated with the reduction in end-systolic volume at follow-up (r=0.66; P<0.001). Baseline Tϵ-SD demonstrated significant correlation with the reduction of end-systolic volume at follow-up (r=0.57; P<0.001); however, baseline tissue velocity–derived dyssynchrony indexes failed to predict the effect of CRT. Conclusions—The strain-derived dyssynchrony index is a better measurement than the tissue velocity dyssynchrony index for monitoring changes in mechanical dyssynchrony after CRT and for predicting reduction in left ventricular volume after CRT.

Aortic Valve Sclerosis and Clinical Outcomes: Moving Toward a Definition

The presence of aortic valve sclerosis has been suggested as a marker of increased cardiovascular risk, including increased mortality. However, it remains unclear whether aortic valve sclerosis is independently associated with risk or merely a marker of coexistent cardiovascular risk factors. Aortic valve sclerosis is usually diagnosed on transthoracic echocardiography, the most widely used imaging modality in observational and natural history studies of aortic valve disease. Defining aortic valve sclerosis has remained challenging due to the variable and qualitative nature of its description by ultrasound techniques. Importantly, artifacts common to ultrasound imaging and awareness of demographic and clinical history information may bias the diagnosis of aortic valve sclerosis. Because clinicians may alter treatment recommendations or follow-up based on echocardiographic reporting of aortic valve sclerosis, highlighting pitfalls of the subjective nature by which aortic valve sclerosis is identified and establishing diagnostic criteria are necessary. This review describes the diagnostic criteria for aortic valve sclerosis used in outcome studies, summarizes the epidemiological findings reporting the relationship between aortic valve sclerosis and clinical outcome, and proposes a definition of aortic valve sclerosis based on the literature.