Morten Dalsgaard

Left Atrial Volume in Patients With Asymptomatic Aortic Valve Stenosis (the Simvastatin and Ezetimibe in Aortic Stenosis Study)

Left atrial (LA) size is known to increase with persistently increased left ventricular (LV) filling pressure. We therefore hypothesized that LA volume might reflect the severity of aortic valve stenosis (AS). Transthoracic echocardiography was performed in 1,758 patients with asymptomatic AS (transaortic Doppler velocity > or =2.5 and < or =4 m/s) in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. LA volume was measured in end-systole in the apical 4-chamber view in 1,503 patients (85%), and aortic valve area (AVA) was estimated by the continuity equation and indexed by body surface area. Mean values for age and AVA were 67 +/- 10 years and 1.27 +/- 0.5 cm2, respectively, and 574 were women (38%). Mean value for LA volume indexed (LAVI) was 36 +/- 13 ml/m2. Enlargement of LA volume (> or =32 ml/m2) was found in 57% of patients. AVA indexed was significantly correlated to LAVI (r = -0.1, p = 0.0002). Multivariate analysis showed that LAVI was significantly related to AVA indexed (beta = -4.1, p = 0.007) in a model that also included mitral regurgitation (beta = 2.8, p <0.0001), history of hypertension (beta = 2.2, p = 0.002), LV end-diastolic volume (beta = 0.05, p <0.0001), presence of LV hypertrophy (beta = 3.4, p <0.0001), and restrictive LV filling pattern (beta = 3.5, p = 0.01). Gender and LV ejection fraction were eliminated from the final model. In conclusion, LA volume is often enlarged in asymptomatic patients with AS. Furthermore, LA volume is related to AVA even when adjusting for other known risk factors for increased LA volume including of measurements of diastolic function.

Troponin T is a strong marker of mortality in hospitalized patients

BACKGROUND Cardiac troponins are diagnostic markers in acute coronary syndrome and prognostic markers in stable coronary disease. Small increases are occasionally observed in patients with non-cardiac disease, but the prevalence and prognostic value of increased troponin in the general hospitalized population are unknown. METHODS Consecutive patients aged >40 years admitted to a district hospital between 1 April 1998 and 31 March 1999 were included. A comprehensive medical interview and clinical examination were performed including echocardiography and measurement of natriuretic peptides and troponin T with a high-sensitivity assay (hs-TnT). RESULTS Serum for analyses of hs-TnT was available from 1176 patients. Patients were 73.7 years old on average (interquartile range, 64.5-80.0 years), 59.2% were women and median follow-up was 11.4 years. The prevalence of elevated hs-TnT (> 99(th) percentile) was 57.1% of the entire cohort and 52.3% of patients with non-cardiac diagnoses. hs-TnT above the median (17 ng/L) was associated in univariate analysis with a 3-fold higher mortality in the entire population (multivariate hazard rate (HR) from 1.3 to 1.8 for 1 and 11 year mortality, respectively). In patients without past or present ischemic heart disease hs-TnT in the upper quartile (above 34.8 ng/L) was associated in univariate analysis with a 5-fold higher mortality risk (multivariable HR 1.8 to 2.2 for 1 and 11 year mortality, respectively). CONCLUSION More than half of the hospitalized patients had hs-TnT levels above the 99(th) percentile. Elevated hs-TnT is a strong mortality risk marker in general hospitalized older patients.

Usefulness of Pregnancy-Associated Plasma Protein A in Patients With Acute Coronary Syndrome

To investigate whether pregnancy-associated plasma protein-A (PAPP-A) is a prognostic marker in patients admitted with high-risk acute coronary syndrome. In patients admitted with high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and ST-segment elevation myocardial infarction (STEMI), risk stratification is primarily determined by the markers of myocardial necrosis and known demographic risk profiles. However, it has recently been proposed that the presence and extent of vulnerable plaques might influence the prognosis significantly. A marker for the vulnerable plaque could identify patients at high risk who would potentially benefit from intensive treatment and surveillance. Two populations of consecutive patients admitted with high-risk NSTE-ACS (n = 123) and STEMI (n = 314) were evaluated with serial measurements of PAPP-A. The incidence of mortality and nonfatal myocardial infarction was prospectively registered for 2.66 to 3.47 years. In the patients with high-risk NSTE-ACS, PAPP-A was related to the risk of nonfatal myocardial infarction (p = 0.02) and death (p = 0.03). This result was consistent on multivariate analysis of the combination of mortality or nonfatal myocardial infarction (odds ratio 2.65, 95% confidence interval 1.40 to 5.03) but not for mortality alone (p = NS). In patients with STEMI, PAPP-A was related to the risk of death (p = 0.01) but not the composite outcome of myocardial infarction and death. This was also true after adjustment for other univariate predictors of death (odds ratio 2.19, 95% confidence interval 1.16 to 4.16). In conclusion, PAPP-A seems to be valuable in predicting the outcomes of patients admitted with high-risk NSTE-ACS or STEMI.

Echocardiographic predictors of exercise capacity and mortality in chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) reduces exercise capacity, but lung function parameters do not fully explain functional class and lung-heart interaction could be the explanation. We evaluated echocardiographic predictors of mortality and six minutes walking distance (6MWD), a marker for quality of life and mortality in COPD.MethodsNinety COPD patients (GOLD criteria) were evaluated by body plethysmography, 6MWD and advanced echocardiography parameters (pulsed wave tissue Doppler and speckle tracking).ResultsMean 6MWD was 403 (± 113) meters. All 90 subjects had preserved left ventricular (LV) ejection fraction 64.3% ± 8.6%. Stroke volume decreased while heart rate increased with COPD severity and hyperinflation. In 66% of patients, some degree of diastolic dysfunction was present. Mitral tissue Doppler data in COPD could be interpreted as a sign of low LV preload and not necessarily an intrinsic impairment in LV relaxation/compliance. Tricuspid regurgitation (TR) increased with COPD severity and hyperinflation. Age (p < 0.001), BMI (p < 0.001), DLCO SB (p < 0.001) and TR (p 0.005) were independent predictors of 6MWD and a multivariable model incorporating heart function parameters (adjusted r2 = .511) compared well to a model with lung function parameters alone (adjusted r2 = .475). LV global longitudinal strain (p = 0.034) was the only independent predictor of mortality among all baseline, body plethysmographic and echocardiographic variables.ConclusionsAmong subjects with moderate to severe COPD and normal LVEF, GLS independently predicted all-cause mortality. Exercise tolerance correlated with standard lung function parameters only in univariate models; in subsequent models including echocardiographic parameters, longer 6MWD correlated independently with milder TR, better DLCO SB, younger age and lower BMI. We extended the evidence on COPD affecting cardiac chamber volumes, LV preload, heart rate, as well as systolic and diastolic function. Our results highlight lung-heart interaction and the necessity of cardiac evaluation in COPD.

Left atrial size and function as predictors of new-onset of atrial fibrillation in patients with asymptomatic aortic stenosis: The simvastatin and ezetimibe in aortic stenosis study

BACKGROUND Left atrial (LA) size and function change with chronically increased left ventricular (LV) filling pressures. It remains unclear whether these variations in LA parameters can predict new-onset atrial fibrillation (AF) in asymptomatic patients with aortic stenosis (AS). METHODS Data were obtained in asymptomatic patients with mild-to-moderate AS (2.5 ≤ transaortic Doppler velocity ≤ 4.0m/s), preserved LV ejection fraction (EF), no previous AF, and were enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study. Peak-aortic velocity, LA(max) volume & LAmin volume were measured by echocardiography. LA conduit (LA(con)) volume was defined as LV stroke volume-LA stroke volume. LA function was expressed as LA-EF (LA(max)-LAmin volume/LA(max)). RESULTS In the 1159 patients included, new-onset AF occurred in 71 patients (6.1%) within a mean follow-up of 4.2 ± 0.9 years. Mean age was 66 ± 9.7 years, aortic valve area index 0.6 ± 0.2 cm(2)/m(2), LV mass 99.2 ± 29.7 g/m(2), LA(max) volume 34.6 ± 12.0 mL/m(2), LAmin volume 17.9 ± 9.3 mL/m(2), LA-EF 50 ± 15% and LA(con) volume 45 ± 21 mL/m(2). Baseline LAmin volume predicted new-onset AF in Cox multivariable analysis (HR:2.3 [95%CI:1.3-4.4], P<0.01), and added prognostic information on AF development beyond conventional risk factors (likelihood ratio, P<0.01). In comparison of c-indexes LAmin volume was superior to all other LA measurements. Net reclassification index improved by 15.9% when adding LAmin volume to a model with classic risk factors for AF (P=0.01). CONCLUSION LAmin volume independently predicted new-onset AF in patients with asymptomatic AS and was superior to LA-EF, LA(con) and LA(max) volumes and conventional risk factors.

Pregnancy-associated plasma protein-A, a marker for outcome in patients suspected for acute coronary syndrome.

OBJECTIVES To examine if pregnancy-associated plasma protein-A (PAPP-A) in patients with chest pain, could identify patients at risk for death or myocardial infarction. DESIGN AND METHODS Patients admitted with chest pain and both normal ECG and normal biomarkers were evaluated by serial measurement of PAPP-A. Main outcome measures were mortality and non-fatal myocardial infarction. RESULTS Median age of patients included (415) was 67years and 43% were women. The risk of death or non-fatal myocardial infarction after 3 months was 15% in the highest quartile of circulating PAPP-A compared with 3% in the lowest quartile (relative risk 3.7, p<0.01). Corresponding numbers after 1 year were 24% and 10% (relative risk 2.4, p=0.01). CONCLUSION In patients admitted with chest pain and both normal ECG and normal biomarkers PAPP-A seems to be valuable for predicting patients at high risk of death or non-fatal myocardial infarction.

Short-term hemodynamic effect of angiotensin-converting enzyme inhibition in patients with severe aortic stenosis: a placebo-controlled, randomized study.

BACKGROUND In patients with severe aortic stenosis (AS), treatment with angiotensin-converting enzyme inhibitors has previously been considered contraindicated. However, there is a lack of clinical evidence to confirm these potential hemodynamic risks and benefits. METHODS Forty-four patients with severe AS (aortic valve area <1 cm(2)) were randomized to treatment with trandolapril 22 mg daily/placebo (1:1). Right heart catheterization and echocardiography were performed at rest and during exercise at baseline and on day 3. Follow-up was performed before valve replacement or after a maximum of 8 weeks, when exercise echocardiography was repeated. RESULTS Compared with placebo, systolic blood pressure and systemic arterial compliance significantly changed at day 3 (-14 ± 11 vs -5 ± 13 mm Hg, P = .02, and 0.08 ± 0.16 vs -0.05 ± 0.86 mL/m(2) per mm Hg, P = .03, respectively). Changes in left ventricular end systolic volume (LVESV) was nonsignificant (-8 ± 9 vs -3 ± 11 mL, P = .17). At a median of 49 days of follow-up, changes in LVESV and N-terminal pro-brain natriuretic peptide were even lower revealing significant differences between the groups (-7.8 ± 2.6 vs -0.5 ± 2.5 mL, P = .04, and -19 ± 7 vs 0.8 ± 6 pmol/L, P = .04, respectively). No episodes of symptomatic hypotension were noted, and other hemodynamic parameters remained unchanged. CONCLUSION Angiotensin-converting enzyme inhibition in severe AS caused a decrease in LVESV and N-terminal pro-brain natriuretic peptide with other hemodynamic parameters preserved both at rest and during exercise implying hemodynamic improvement with left ventricular unloading.

Risk stratification in emergency patients by copeptin

BackgroundRapid risk stratification is a core task in emergency medicine. Identifying patients at high and low risk shortly after admission could help clinical decision-making regarding treatment, level of observation, allocation of resources and post discharge follow-up. The purpose of the present study was to determine short-, mid- and long-term mortality by plasma measurement of copeptin in unselected admitted patients.MethodConsecutive patients >40-years-old admitted to an inner-city hospital were included. Within the first 24 hours after admission, a structured medical interview was conducted and self-reported medical history was recorded. All patients underwent a clinical examination, an echocardiographic evaluation and collection of blood for later measurement of risk markers.ResultsPlasma for copeptin measurement was available from 1,320 patients (average age 70.5 years, 59.4% women). Median follow-up time was 11.5 years (range 11.0 to 12.0 years). Copeptin was elevated (that is, above the 97.5 percentile in healthy individuals).Mortality within the first week was 2.7% (17/627) for patients with elevated copeptin (above the 97.5 percentile, that is, >11.3 pmol/L) compared to 0.1% (1/693) for patients with normal copeptin concentrations (that is, ≤11.3 pmol/L) (P <0.01). Three-month mortality was 14.5% (91/627) for patients with elevated copeptin compared to 3.2% (22/693) for patients with normal copeptin. Similar figures for one-year mortality and for the entire observation period were 27.6% (173/627) versus 8.7% (60/693) and 82.9% (520/527) versus 57.5% (398/693) (P <0.01 for both), respectively.Using multivariable Cox regression analyses shows that elevated copeptin was significantly and independently related to short-, mid- and long-term mortality. Adjusted hazard ratios were 2.4 for three-month mortality, 1.9 for one-year mortality and 1.4 for mortality in the entire observation period.ConclusionsIn patients admitted to an inner-city hospital, copeptin was strongly associated with short-, mid- and long-term mortality. The results suggest that rapid copeptin measurement could be a useful tool for both disposition in an emergency department and for mid- and long-term risk assessment.

Left Atrial Systolic Force and Outcome in Asymptomatic Mild to Moderate Aortic Stenosis

Background and Aims: In patients with chronic pressure overload due to hypertension or aortic valve stenosis (AS), higher left atrial systolic force (LASF) is associated with a high‐risk cardiovascular (CV) phenotype. We tested LASF as prognostic marker in patients with AS. Methods: We used baseline and outcome data from 1,566 patients recruited in the Simvastatin and Ezetimibe in AS (SEAS) study evaluating the effect of placebo‐controlled simvastatin and ezetimibe treatment on CV events. The primary outcome was a composite of major CV events, including CV death, aortic valve replacement, nonfatal myocardial infarction, hospitalization for unstable angina, heart failure caused by progression of AS, coronary artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. LASF was calculated by Mannings method. High LASF was defined as >95th percentile (50 Kdynes/cm2) of the distribution within the study population. Results: During 4.3 years of follow‐up, a major CV event occurred in 38 of 78 patients with high LASF (49%) and in 513 of 1,488 (34%) with normal LASF (P = 0.01). In multivariate Cox regression analysis, high LASF predicted higher rate of major CV events (Hazard ratio 1.43 [95% confidence interval 1.01–2.03] independent of aortic valve area and LV mass index. A simple risk score including absence or presence of these three variables allowed risk stratification into low, intermediate, high and very high risk for major CV events during follow‐up (22%, 28%, 38%, and 53%, respectively). Conclusions: Higher LASF provides additional prognostic information in patients with asymptomatic mild‐to‐moderate AS.

Left Atrial Systolic Force in Asymptomatic Aortic Stenosis

Background: There is a limited knowledge about left atrial (LA) systolic force (LASF) and its key determinants in patients with asymptomatic mild–moderate aortic stenosis (AS). Methods: We used baseline clinic and echocardiographic data from 1,566 patients recruited in the simvastatin ezetimibe in aortic stenosis study evaluating the effect of placebo‐controlled combined simvastatin and ezetimibe treatment in asymptomatic AS. The LASF was calculated by Mannings method. Low and high LASF were defined as <5th and >95th percentile of the distribution within the study population, respectively. Results: Mean LASF in the total study population was 21 ± 14 kdynes/cm2. The determinants of LASF were higher age, heart rate, body mass index, systolic blood pressure, left ventricular (LV) mass, mitral peak early velocity, maximal LA volume, and longer mitral deceleration time (multiple R2= 0.37, P < 0.01). High LASF (78 patients) was characterized by abnormal LV relaxation in 90% of the cases. Low LASF (82 patients) was associated with restrictive LV filling pattern, absence of abnormal relaxation pattern, smaller maximal LA volume, and lower body mass index. In 40% of the patients with low LASF, estimated LV filling pressures were normal and the reduced LA force was explainable by an intrinsic systolic LA dysfunction. Conclusions: In patients with asymptomatic AS, LASF was closely related to filling pressure. Higher LASF invariably signifies the maximal LA effort to keep near normal LV filling pressure; lower LASF belongs to a heterogeneous group of patients in which it is much more difficult to depict who have low LA preload or who have intrinsic systolic LA dysfunction. (Echocardiography 2011;28:968‐977)