Christopher G. Scott

Burden of valvular heart diseases: a population-based study

BACKGROUND Valvular heart diseases are not usually regarded as a major public-health problem. Our aim was to assess their prevalence and effect on overall survival in the general population. METHODS We pooled population-based studies to obtain data for 11 911 randomly selected adults from the general population who had been assessed prospectively with echocardiography. We also analysed data from a community study of 16 501 adults who had been assessed by clinically indicated echocardiography. FINDINGS In the general population group, moderate or severe valve disease was identified in 615 adults. There was no difference in the frequency of such diseases between men and women (p=0.90). Prevalence increased with age, from 0.7% (95% CI 0.5-1.0) in 18-44 year olds to 13.3% (11.7-15.0) in the 75 years and older group (p<0.0001). The national prevalence of valve disease, corrected for age and sex distribution from the US 2000 population, is 2.5% (2.2-2.7). In the community group, valve disease was diagnosed in 1505 (1.8% adjusted) adults and frequency increased considerably with age, from 0.3% (0.2-0.3) of the 18-44 year olds to 11.7% (11.0-12.5) of those aged 75 years and older, but was diagnosed less often in women than in men (odds ratio 0.90, 0.81-1.01; p=0.07). The adjusted mortality risk ratio associated with valve disease was 1.36 (1.15-1.62; p=0.0005) in the population and 1.75 (1.61-1.90; p<0.0001) in the community. INTERPRETATION Moderate or severe valvular diseases are notably common in this population and increase with age. In the community, women are less often diagnosed than are men, which could indicate an important imbalance in view of the associated lower survival. Valve diseases thus represent an important public-health problem.

Outcome of 622 Adults With Asymptomatic, Hemodynamically Significant Aortic Stenosis During Prolonged Follow-Up

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.

Atrial fibrillation complicating the course of degenerative mitral regurgitation: Determinants and long-term outcome

OBJECTIVES The study was done to define the incidence, determinants and prognostic implications of onset of atrial fibrillation (AF) during follow-up of mitral regurgitation (MR) initially in sinus rhythm. BACKGROUND The rates and clinical implications of AF in MR are undefined. METHODS We analyzed the occurrence of AF under conservative management in two populations of patients with degenerative MR in sinus rhythm at diagnosis: 1) 360 patients (65 +/- 13 years, 74% men) with MR due to flail leaflets; and 2) 89 residents of Olmsted County, Minnesota (67 +/- 17 years, 56% men) with grade 3 or 4 MR due to simple mitral valve prolapse (MVP) diagnosed echocardiographically. RESULTS In patients with MR due to flail leaflets, AF rates at 5 and 10 years were 18 +/- 3% and 48 +/- 6%, respectively, and the linearized rate was 5.0 +/- 0.7% per year. Development of AF during follow-up was independently associated with high risk of cardiac death or heart failure (adjusted risk ratio 2.23, p = 0.025). The AF rate at 10 years was higher in patients >or=65 years (75 +/- 10% vs. 24 +/- 6%, p < 0.0001) and in those with baseline left atrial (LA) dimension >or=50 mm (67 +/- 8% vs. 37 +/- 9%, p < 0.001). In multivariate analysis, independent baseline predictors of AF were age and LA diameter (both p < 0.01). In patients with MR due to MVP, similar rates of AF (41 +/- 7% vs. 44 +/- 6% at nine years, p > 0.50) and predictors of AF (age and LA dimension, both p < 0.006) were noted. CONCLUSIONS In patients with degenerative MR in sinus rhythm at diagnosis, the incidence of AF occurring under conservative management is high and similar whether the cause of MR is flail leaflet or simple MVP. After onset of AF, an increased cardiac mortality and morbidity are both observed under conservative management. The risk of AF increases with advancing age and larger LA dimension. These data suggest that the clinical management of MR should take into account the high incidence, excess risk, and predictors of AF.

B-type natriuretic peptide in organic mitral regurgitation : Determinants and impact on outcome

Background—B-type natriuretic peptide (BNP) activation observed in cardiac diseases is a predictor of poor outcome; however, in organic mitral regurgitation (MR), BNP determinants and prognostic value are unknown. Methods and Results—We prospectively enrolled 124 patients with chronic organic MR (aged 63±15 years, 60% males) in whom we measured BNP level and simultaneously quantified MR degree, left ventricular (LV) remodeling, and left atrial (LA) volumes and analyzed long-term outcome. Baseline BNP level (54±67 pg/mL, median 31 pg/mL) was associated univariately with multiple clinical and echocardiographic characteristics, but in multivariate analysis, independent determinants of BNP, beyond age and sex (both P≤0.01), were LV end-systolic volume index, LA volume, atrial fibrillation, and symptoms (all P<0.02). Conversely, MR degree was not independently associated with BNP. During follow-up, patients with high versus low BNP (≥31 versus <31 pg/mL) displayed lower survival rates (at 5 years, 72±10% versus 95±5%, P=0.03) and higher rates of the combined end point of death and heart failure (at 5 years, 42±10% versus 16±7%, P=0.03). In multivariate analysis, with adjustment for age, sex, functional class, MR severity, and ejection fraction, BNP was independently predictive of mortality (hazard ratio per 10 pg/mL, 1.23 [95% CI 1.07 to 1.48], P=0.004) and of death or heart failure (hazard ratio per 10 pg/mL, 1.09 [95% CI 1.001 to 1.19], P=0.04). Conclusions—BNP activation in organic MR reflects primarily ventricular and atrial consequences rather than degree of MR. Higher BNP level in patients with organic MR independently predicts adverse events under conservative management. Therefore, BNP activation in organic MR is an emerging biomarker of severity of MR consequences and of poor clinical outcome, and its assessment should be considered in the clinical evaluation and risk stratification of patients with MR.

Mammographic Breast Density as a General Marker of Breast Cancer Risk

Mammographic breast density is a strong risk factor for breast cancer but whether breast density is a general marker of susceptibility or is specific to the location of the eventual cancer is unknown. A study of 372 incident breast cancer cases and 713 matched controls was conducted within the Mayo Clinic mammography screening practice. Mammograms on average 7 years before breast cancer were digitized, and quantitative measures of percentage density and dense area from each side and view were estimated. A regional density estimate accounting for overall percentage density was calculated from both mammogram views. Location of breast cancer and potential confounders were abstracted from medical records. Conditional logistic regression was used to estimate associations, and C-statistics were used to evaluate the strength of risk prediction. There were increasing trends in breast cancer risk with increasing quartiles of percentage density and dense area, irrespective of the side of the breast with cancer (Ptrends < 0.001). Percentage density from the ipsilateral side [craniocaudal (CC): odds ratios (ORs), 1.0 (ref), 1.7, 3.1, and 3.1; mediolateral oblique (MLO): ORs, 1.0 (ref), 1.5, 2.2, and 2.8] and the contralateral side [CC: ORs, 1.0 (ref), 1.8, 2.2, and 3.7; MLO: ORs, 1.0 (ref), 1.6, 1.9, and 2.5] similarly predicted case-control status (C-statistics, 0.64-65). Accounting for overall percentage density, density in the region where the cancer subsequently developed was not a significant risk factor [CC: 1.0 (ref), 1.3, 1.0, and 1.2; MLO: 1.0 (ref), 1.1, 1.0, and 1.1 for increasing quartiles]. Results did not change when examining mammograms 3 years on average before the cancer. Overall mammographic density seems to represent a general marker of breast cancer risk that is not specific to breast side or location of the eventual cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(1):43–9)

Outcomes After Aortic Valve Replacement in Patients With Severe Aortic Regurgitation and Markedly Reduced Left Ventricular Function

Background—Left ventricular dysfunction is an indication for aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR). However, the postoperative outcome of patients with severe AR and a markedly low ejection fraction (EF) is not known. Methods and Results—The study group consisted of a total of 450 patients who had AVR for isolated AR between 1980 and 1995. Patients with markedly reduced left ventricular function (EF <35%, LoEF, n=43) were compared with those with moderate reduction in left ventricular function (EF 35% to 50%, MedEF, n=134) and those with normal left ventricular function (EF ≥50%, Nl EF, n=273). The operative mortality rate was higher with LoEF (14%) than with MedEF and Nl EF (6.7% and 3.7%, respectively, P =0.02). At 10 years, 41%±9% of LoEF patients had survived compared with 56%±5% and 70%±3% of MedEF and Nl EF patients, respectively (P <0.0001). Congestive heart failure occurred at 10 years in 25%±9% with LoEF compared with 17%±4% and 9%±2% with MedEF and NL EF, respectively (P <0.003). Postoperative EF improved by 4.9%±13.8% in the LoEF group and by 4%±11.9% in the MedEF group compared with −2.3%±10.9% in the Nl EF group (P <0.002 and P <0.0001, respectively). Conclusions—Patients with severe AR and markedly low EF incur excess operative mortality rates, postoperative mortality rates, and congestive heart failure after AVR. However, postoperative EF improves markedly, and most patients enjoy a long postoperative survival without recurrence of heart failure after AVR; thus they should not be denied the benefits of AVR.

Flow-Gradient Patterns in Severe Aortic Stenosis With Preserved Ejection Fraction Clinical Characteristics and Predictors of Survival

Background— Among patients with severe aortic stenosis (AS) and preserved ejection fraction, those with low gradient (LG) and reduced stroke volume may have an adverse prognosis. We investigated the prognostic impact of stroke volume using the recently proposed flow-gradient classification. Methods and Results— We examined 1704 consecutive patients with severe AS (aortic valve area <1.0 cm2) and preserved ejection fraction (≥50%) using 2-dimensional and Doppler echocardiography. Patients were stratified by stroke volume index (<35 mL/m2 [low flow, LF] versus ≥35 mL/m2 [normal flow, NF]) and aortic gradient (<40 mm Hg [LG] versus ≥40 mm Hg [high gradient, HG]) into 4 groups: NF/HG, NF/LG, LF/HG, and LF/LG. NF/LG (n=352, 21%), was associated with favorable survival with medical management (2-year estimate, 82% versus 67% in NF/HG; P<0.0001). LF/LG severe AS (n=53, 3%) was characterized by lower ejection fraction, more prevalent atrial fibrillation and heart failure, reduced arterial compliance, and reduced survival (2-year estimate, 60% versus 82% in NF/HG; P<0.001). In multivariable analysis, the LF/LG pattern was the strongest predictor of mortality (hazard ratio, 3.26; 95% confidence interval, 1.71–6.22; P<0.001 versus NF/LG). Aortic valve replacement was associated with a 69% mortality reduction (hazard ratio, 0.31; 95% confidence interval, 0.25–0.39; P<0.0001) in LF/LG and NF/HG, with no survival benefit associated with aortic valve replacement in NF/LG and LF/HG. Conclusions— NF/LG severe AS with preserved ejection fraction exhibits favorable survival with medical management, and the impact of aortic valve replacement on survival was neutral. LF/LG severe AS is characterized by a high prevalence of atrial fibrillation, heart failure, and reduced survival, and aortic valve replacement was associated with improved survival. These findings have implications for the evaluation and subsequent management of AS severity.

The benefits of early valve replacement in asymptomatic patients with severe aortic stenosis

OBJECTIVE The prevalence of aortic valve stenosis increases with age, and often the diagnosis is made by echocardiography before symptoms develop. To address the controversies in management of asymptomatic patients with severe aortic stenosis, we assessed the early and late outcomes of aortic valve replacement in these patients. METHODS We analyzed data of 622 patients, aged 72 +/- 11 years, with isolated asymptomatic severe aortic stenosis. Patients were identified with a peak systolic velocity of greater than 4 m/s by transthoracic echocardiography and monitored for the development of symptoms and need for aortic valve replacement. RESULTS After the initial diagnosis, 166 (27%) patients who were initially asymptomatic experienced the development of chest pain, shortness of breath, or syncope and had aortic valve replacement at Mayo Clinic. Another 97 (16%) patients had aortic valve replacement in the absence of symptoms. Symptomatic patients were more likely to undergo coronary bypass grafting (P < .01) and have diabetes, hypercholesterolemia, and a lower ejection fraction (P < .05 for each). Operative mortality was 2% for symptomatic patients and 1% for asymptomatic patients (P = .43). The survival of the 263 patients who underwent aortic valve replacement was not significantly different from an age- and sex-matched population (P = .99); 10-year survival was 64% (95% confidence interval [CI] 57%-72%) for symptomatic patients and 64% (95% CI 54%-75%) for asymptomatic patients (P = .92). At 3 years after diagnosis of severe aortic stenosis, 52% (95% CI 48%-56%) of 622 patients had had symptoms develop, undergone aortic valve replacement, or died. Among the entire cohort, older age at diagnosis (hazard ratio [HR] 1.1 per year, P < .001), diabetes (HR 1.7, P < .001), decreased ejection fraction (HR 1.1 per 1% downward arrow, P = .01), symptoms (HR 2.13, P < .001), and absence of aortic valve replacement (HR 3.53, P < .001) were identified as independent risk factors for mortality. CONCLUSION Among patients with severe aortic stenosis who underwent aortic valve replacement, early and late outcomes were similarly good in patients who had symptoms before the operation compared with those who were asymptomatic. It is important to note that among patients with asymptomatic severe aortic stenosis, the omission of surgical treatment was the most important risk factor for late mortality.

Surgical Correction of Mitral Regurgitation in the Elderly Outcomes and Recent Improvements

Background— In the elderly, mitral regurgitation (MR) is frequent, but surgery risks are considered high. Benefits and indications of MR surgery are uncertain in the elderly. Methods and Results— Baseline characteristics, outcome, and trends for surgical results improvement were analyzed in elderly patients (≥75 years of age; n=284) operated on for MR in 1980 to 1995 compared with younger patients (65 to 74 years of age, n=504; and <65 years of age, n=556). Preoperatively, class III to IV symptoms, atrial fibrillation, coronary disease, creatinine, and comorbidity index were more severe in elderly patients (all p<0.002). In the long term after surgery, observed survival stratified by age (≥75, 65 to 74, <65 years) was lower in elderly than in younger patients (at 5 years, 57±3%, 73±2%, and 85±2%, respectively; P<0.001), but ratios of observed to expected survival were similar (83%, 85%, and 88%, respectively). In multivariate analysis adjusted to expected survival, elderly patients showed no difference in life expectancy restoration compared with younger patients (adjusted hazard ratio, 0.89; 95% confidence interval, 0.73 to 1.30; P=0.54). Temporal trends showed that risk of operative mortality, although higher in elderly patients (P<0.001), declined markedly for all ages (27% to 5% in those ≥75 years of age, P<0.01; 21% to 4% in those 65 to 74 years of age, P<0.01; and 7% to 2% in those <65 years of age, P=0.06), with a parallel decline in low cardiac output and length of hospital stay. Over time, valve repair feasibility increased in all age groups (30% to 84% overall and 31% to 93% in degenerative MR; P<0.0001). Conclusions— Elderly patients undergoing MR surgery display more severe preoperative characteristics and incur higher operative risks than younger patients. However, restoration of life expectancy after surgery is similar in elderly and younger patients, and outstanding recent surgical improvements particularly benefited elderly patients. Thus, elderly patients with MR can now carefully be considered for surgery before refractory heart failure is present.

Mammographic Density Phenotypes and Risk of Breast Cancer: A Meta-analysis

BACKGROUND Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk. METHODS We conducted a meta-analysis of 13 case-control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk. We used random-effects models to calculate pooled odds ratios and 95% confidence intervals (CIs). All tests were two-sided with P less than .05 considered to be statistically significant. RESULTS Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95% CI = 1.29 to 1.47) for absolute dense area, 0.78 (95% CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95% CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11187 control subjects) were 1.38 (95% CI = 1.31 to 1.44), 0.79 (95% CI = 0.73 to 0.85), and 1.53 (95% CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95% CI = 0.71 to 0.94; P heterogeneity = .02) for premenopausal and 0.85 (95% CI = 0.75 to 0.96; P heterogeneity < .01) for postmenopausal women. CONCLUSIONS The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area.