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.

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 (ß ± 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.

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.

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.

Use of B-type natriuretic peptide as a screening tool for left ventricular diastolic dysfunction in rheumatoid arthritis patients without clinical cardiovascular disease.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at an increased risk for heart failure and left ventricular diastolic dysfunction (LVDD). B-type natriuretic peptide (BNP) may be useful to screen for LVDD in the general population. We compared the effectiveness of BNP as a screening tool for LVDD in RA and non-RA subjects without cardiovascular disease (CVD). METHODS: Study subjects were recruited from population-based samples with and without RA, excluding subjects with CVD. LVDD was assessed by 2-dimensional and Doppler echocardiography and categorized as none, mild, moderate/severe, or indeterminate. Linear regression and proportional odds models evaluated the association between LVDD and BNP, adjusting for age, sex, and body mass index. RESULTS: Among 231 RA and 1,730 non-RA subjects without CVD, BNP was significantly higher in subjects with moderate/severe LVDD compared to those with no or mild LVDD (P = 0.02 for RA and P < 0.001 for non-RA subjects). More RA subjects had elevated BNP than non-RA subjects (16% versus 9%; P < 0.001). Positive predictive value (25% in RA and 18% in non-RA subjects) and sensitivity (40% in RA and 26% in non-RA subjects) were similarly low in both cohorts, but specificity was significantly lower in RA than in non-RA subjects (89% versus 94%; P = 0.02). CONCLUSION: While RA subjects were more likely to have elevated BNP, few RA patients with elevated BNP actually have LVDD. Also, normal BNP levels are less likely to rule out LVDD in RA than in non-RA subjects. Therefore, BNP may be less effective for screening in RA subjects compared to the general population.

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> or =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.

CT of left ventricular assist devices.

Left ventricular assist devices (LVADs) have become an increasingly beneficial option for patients with heart failure, especially in light of the insufficient availability of donor hearts. LVADs have been used effectively in end-stage heart failure as a bridge to heart transplantation, as destination therapy for those ineligible for transplantation, or as a bridge to myocardial recovery. Presently, a wide variety of LVADs are being used therapeutically. Four different LVADs have been used at the authors' institution. The records of 42 patients who underwent implantation of 46 total LVADs during a 17-month period were reviewed; in 23 of these patients, computed tomography of the device was performed. Increased use of LVADs necessitates understanding of the normal positioning of a variety of these devices and recognition of potential complications, which include inflow and outflow cannula complications, postoperative hemorrhage, pericardial tamponade, thrombus formation, aortic valve stenosis, aortic valve insufficiency, right-sided heart failure, and infection.

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 Foundation's 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.

The effects of nesiritide on renal function and diuretic responsiveness in acutely decompensated heart failure patients with renal dysfunction.

BACKGROUND: Strategies to preserve renal function and enhance diuretic responsiveness during therapy for heart failure (HF) are needed. We hypothesized that brain natriuretic peptide (nesiritide) added to standard HF therapy would preserve renal function and enhance diuretic responsiveness. METHODS: Patients with HF with underlying renal dysfunction who were admitted with volume overload were randomized to standard therapy with nesiritide (2 mug/kg bolus; 0.01 mug/kg/min for 48 hours) or without nesiritide. Patients requiring intravenous vasodilator or inotropic therapy for rapid symptom relief were ineligible. In all patients, diuretics were administered according to a standardized dosing algorithm. RESULTS: Patients (n = 72) had a mean creatinine level of 1.75 +/- 0.59 mg/dL. Patients receiving nesiritide had a lesser increase in creatinine (P = .048) and blood urea nitrogen (P = .02), but a greater reduction in blood pressure (P < .01). Nesiritide did not enhance diuretic responsiveness (P = .57) but increased 3'5' cyclic guanosine monophosphate and decreased endothelin more (P < .05 for both). There were no differences in the change in atrial natriuretic peptide, N-terminal pro-brain natriuretic peptide, plasma renin activity, angiotensin II, and aldosterone between groups. CONCLUSION: When used as adjuvant "renal protective" therapy in patients with HF with renal dysfunction, the recommended dose of nesiritide reduced blood pressure, did not seem to worsen renal function, and suppressed endothelin but did not enhance diuretic responsiveness or prevent activation of the renin-angiotensin-aldosterone system.

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 (Tepsilon-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 Tepsilon-SD decreased significantly after CRT (P<0.001). Improvement in Tepsilon-SD 1 day after CRT correlated with the reduction in end-systolic volume at follow-up (r=0.66; P<0.001). Baseline Tepsilon-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.

Use of a novel ultrafiltration device as a treatment strategy for diuretic resistant, refractory heart failure: initial clinical experience in a single center.

BACKGROUND: The System 100 UF device allows ultrafiltration (UF) via peripheral access and is approved for use in heart failure (HF), although clinical trials defining optimal target population and clinical utility are lacking. We report our initial experience with clinical use of this system in very advanced, diuretic resistant HF patients. METHODS AND RESULTS: Eleven HF patients (mean age 70 years) underwent 1 to 5 UF treatments each (total 32 UF). The goal was to remove 4 liters of fluid per 8-hour UF. Baseline creatinine averaged 2.2 mg/dL (range .9-3.2) while estimated glomerular filtration rates (GFRs) averaged 38 mL/min (range 20-87). Nine patients (82%) had moderate (GFR 30-59; n = 3) or severe (GFR <30; n = 6) renal dysfunction. Nine patients (82%) had documented right ventricular dysfunction, 6 with severe tricuspid regurgitation. Average daily intravenous furosemide dose prior to UF was 258 mg (range 80-480). Patients had received nesiritide (n = 4), dopamine (n = 4), and zaroxylyn (n = 7) prior to UF. Of the 32 UF treatments, 13 (41%) removed >3500 mL, 11 (34%) removed 2500-3500 mL, and 8 (25%) removed <2500 mL. Only one UF treatment (3%) was aborted due to hypotension. There were no significant complications related to UF. Five patients (45%) experienced an increase in creatinine of >.3 mg/dl. Five patients required dialysis for persistent diuretic resistant volume overload or uremic symptoms. Six-month mortality was 55%. CONCLUSIONS: Peripheral UF safely but variably removed fluid. In this very high-risk, advanced HF population, 45% of patients developed worsening renal function during UF therapy. Controlled studies are needed to determine the impact of UF on renal function and outcomes in high-risk populations such as this.

Giant coronary artery aneurysm causing superior vena cava syndrome and congestive heart failure.

Coronary artery aneurysms are defined as localized coronary artery dilations >1.5 times the diameter of the adjacent segments. In adults, they are commonly of atherosclerotic origin and are usually asymptomatic. This is the first case report of a coronary artery aneurysm causing superior vena cava syndrome and heart failure. Chest x-ray showed cardiomegaly, and transthoracic echocardiography showed a mass that was confirmed by transesophageal echocardiography, computed tomography, and coronary angiography. In conclusion, giant coronary artery aneurysms can cause superior vena cava syndrome.

Diastolic dysfunction and left atrial volume: a population-based study.

OBJECTIVES: We examined the association between diastolic function and left atrial volume indexed to body surface area (LAVi) in a population-based study. BACKGROUND: Atrial enlargement has been suggested as a marker of the severity and duration of diastolic dysfunction (DD). However, the association between DD and atrial enlargement and their individual prognostic implications in the population is poorly defined. METHODS: A cross-sectional sample of Olmsted County, Minnesota, residents > or =45 years of age (n=2,042) underwent comprehensive Doppler echocardiography and medical record review. RESULTS: The LAVi increased with worsening DD: 23 +/- 6 ml/m2 (normal), 25 +/- 8 ml/m2 (grade I DD), 31 +/- 8 ml/m2 (grade II DD), 48 +/- 12 ml/m2 (grades III to IV DD). In bivariate analyses, age, left ventricular mass index, and DD grade were positively associated, whereas female gender and ejection fraction (EF) were inversely associated with LAVi (p <0.001 for all). When controlling for age, gender, cardiovascular (CV) disease, EF, and left ventricular mass, grade II DD was associated with a 24%, and grade III to IV DD was associated with a 62% larger LA volume (p <0.0001 for both). The area under the receiver-operator characteristic curve for LAVi to detect grade I, grade II, or grade III to IV DD was 0.57, 0.81, and 0.98, respectively. Both DD and LAVi were predictive of all-cause mortality, but when controlling for DD, LAVi was not an independent predictor of mortality. CONCLUSIONS: These data suggest that DD contributes to LA remodeling. Indeed, DD is a stronger predictor of mortality; presumably it better reflects the impact of CV disease within the general population.