Echocardiographic subtypes of heart failure in consecutive hospitalised patients with dyspnoea.

Heart failure with preserved ejection fraction (HFpEF) involves half of hospitalised patients with heart failure (HF), but estimates vary due to unclear diagnostic criteria. We performed a prospective observational study of hospitalised patients admitted with dyspnoea. The aim was to apply contemporary guidelines to diagnose HF due to valvular disease (HFvhd), HF due to reduced ejection fraction (HFrEF), HF due to midrange EF (HFmrEF) and HFpEF in relation to presumed cardiac or non-cardiac dyspnoea. Methods: We included consecutive hospitalised patients with presumed HF or dyspnoea and excluded patients with acute coronary syndrome, estimated glomerular filtration rate <30 mL/min/1.73 m² or low NT-proBNP (<296 ng/L). Higher age-adjusted NT-proBNP values excluded patients with presumptive non-cardiac dyspnoea. Contemporary criteria for HFpEF and diastolic dysfunction were assessed, and we adjudicated whether acute decompensated HF (ADHF) had been the primary diagnosis. Results: Of 707 eligible patients, we included 370 patients of whom 75 had non-cardiac dyspnoea. Of these, 10% (38/370) had no cardiac dysfunction. Cardiac dysfunction consisted of 18.4%, HFvhd, 30.1% HFrEF, 10.2% HFmrEF and 41.3% HFpEF. HFpEF was twice as common in presumptive non-cardiac dyspnoea versus cardiac dyspnoea (71% vs 34%, p<0.0001). However, adjudicated ADHF was the primary diagnosis in 80% of HFrEF, 62% of HFmrEF and just 28% of HFpEF. Conclusion: HF according to contemporary criteria applied to 90% of patients admitted with dyspnoea and elevated NT-proBNP irrespective of the presumptive cause of dyspnoea, of whom 10% had HFmrEF and 41% HFpEF. However, significant non-cardiac diagnoses related to 9 out of 10 with HFpEF with pulmonary disease as the predominant adjudicated problem.

Troponin T and N-terminal pro B-Type natriuretic peptide and presence of coronary artery disease.

BACKGROUND: We tested the effects of exercise intensity, sampling intervals, degree of coronary artery stenosis, and demographic factors on circulating N-terminal pro B-Type natriuretic peptide (NT-pro-BNP) and cardiac Troponin T (cTnT) in subjects suspected of coronary artery disease (CAD). MATERIALS AND METHODS: A total of 242 subjects referred for diagnostic evaluation of possible CAD had blood samples obtained before, 5 min after, and again 20 h after a symptom-limited exercise test. RESULTS: Totally 40 subjects had CAD with ≥ 50% stenosis, 115 subjects had no stenosis and 87 subjects served as controls. In univariate analysis CAD-subjects had higher median baseline NT-pro-BNP-levels (85.3 ng/L) compared with non-CAD-subjects (41.3 ng/L) and controls (40.1 ng/L), both p < 0.001, but the association disappeared in multivariate analysis adjusted for age and gender. NT-pro-BNP increased similarly after exercise in CAD-subjects, non-CAD-subjects, and controls (median increase 8.14 ng/L) and the increase was positively associated with baseline NT-pro-BNP but not presence of CAD. Median baseline cTnT was 6.25 ng/L in CAD-subjects and 3.00 ng/L in non-CAD-subjects as well as controls, both p < 0.0001. Median ΔcTnT (baseline to 20 h after exercise) was higher in CAD-subjects than non-CAD-subjects and controls (0.62 ng/L vs. 0.0 ng/L, p < 0.001). A linear relationship between ΔcTnT and 'percent of predicted maximal heart rate achieved' was found in subjects with ≥ 70% stenosis (n = 24, r = 0.4067 p = 0.046). CONCLUSIONS: Baseline cTnT and ΔcTnT were found to be independently associated with CAD and also with exercise intensity in stable chest pain subjects. These properties were not identified for NT-pro-BNP.

High-sensitivity C-reactive protein and exercise-induced changes in subjects suspected of coronary artery disease.

BACKGROUND: Inflammation plays a major role in the development of atherosclerosis. We wanted to investigate the effects of exercise on high-sensitivity (hs) C-reactive protein (CRP) in subjects who were suspected of having coronary artery disease (CAD). METHODS: Blood samples were obtained before, 5 minutes after, and 20 hours after an exercise test in 155 subjects who were suspected of CAD. Coronary anatomy was evaluated by computed tomography coronary angiography and/or coronary angiography. RESULTS: Median baseline hs-CRP was higher in subjects with ≥50% coronary artery lumen diameter stenosis (n=41), compared with non-CAD-subjects (n=114), 2.93 mg/L (interquartile range 1.03-5.06 mg/L) and 1.30 mg/L (interquartile range 0.76-2.74 mg/L), respectively, P=0.007. In multivariate analyses testing conventional risk factors, hs-CRP proved borderline significant, odds ratio =2.32, P=0.065. Adding baseline hs-CRP to the results of the exercise test did not improve the diagnostic evaluation. Baseline natural logarithm (Ln) hs-CRP was positively associated with body mass index and baseline Ln-transformed hs troponin T levels, and negatively associated with the daily life activity level. An increase in hs-CRP of 0.13 mg/L (interquartile range 0.05-0.24 mg/L) from baseline to 5 minutes after peak exercise was found (P<0.0001), but the increase was not associated with presence of CAD. From baseline to 20 hours after exercise, no increase in hs-CRP was found. CONCLUSION: In conclusion, hs-CRP was not independently associated with CAD. Hs-CRP increased immediately as a response to the exercise, and the increase was modest and not associated with CAD. The results indicate that exercise has potential to cause unwanted variations in hs-CRP and that exercise prior to hs-CRP measurements in subjects included in epidemiological studies, therefore, should be avoided.

Diagnostic value of exercise-induced changes in circulating high sensitive troponin T in stable chest pain patients.

OBJECTIVE: We investigated the diagnostic value of exercise-induced increase in cardiac Troponin T (cTnT) in stable chest pain subjects. METHODS: CTnT was measured before and 20 h after an exercise test in 157 subjects suspected of coronary artery disease (CAD). RESULTS: CAD subjects (n = 41) had higher baseline cTnT levels compared to non-CAD subjects (n = 116), 6.39 ng/l and 3.00 ng/l, respectively, p < 0.0001, and were more likely to increase in cTnT (70.7% versus 27.6%, p < 0.0001). Net Reclassification Index for the combined variable was 19%, p = 0.02. CONCLUSIONS: Exercise-induced increase in cTnT was found to be associated with CAD and cTnT measurements improved the diagnostic evaluation.

Prevalence and prognosis of heart failure with preserved ejection fraction and elevated N-terminal pro brain natriuretic peptide: a 10-year analysis from the Copenhagen Hospital Heart Failure Study.

AIMS: The aim of this study was to assess the epidemiological features and prognosis of heart failure with preserved ejection fraction (HFPEF) and to compare these findings with those from patients with reduced ejection fraction. Furthermore the effects of N-terminal pro brain natriuretic peptide (NT-proBNP) requirement in the heart failure diagnosis were assessed by repeating the analyses in the subgroup of patients with elevated NT-proBNP. METHODS AND RESULTS: In 1844 patients admitted, a clinical diagnosis of heart failure was made in 433; amongst these 61% had HFPEF. An elevated NT-proBNP applied to the heart failure diagnosis reduced the number of heart failure patients to 191, and amongst these 29% had preserved ejection fraction. Use of NT-proBNP reduced clinical differences between heart failure patients with preserved and reduced ejection fraction. When not using NT-proBNP, patients with reduced ejection fraction had higher mortality [hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.01-1.52; P = 0.04], even after adjustment for other significant predictors of mortality, except NT-proBNP (HR 1.29, 95% CI 1.04-1.59; P = 0.02). However, no difference in mortality was observed when NT-proBNP was adjusted for (HR 0.90, 95% CI 0.71-1.15; P = 0.4), or used for the heart failure diagnosis (HR 0.96; 95% CI 0.71-1.29; P = 0.8). CONCLUSION: Using a heart failure diagnosis requiring elevated NT-proBNP reduces the prevalence of HFPEF and results in a survival similar to that of heart failure with reduced ejection fraction. In contrast, when NT-proBNP is not used for the heart failure diagnosis or adjusted for, HFPEF is associated with a lower mortality in both univariate and multivariate analysis.

Electrocardiographic features of sarcomere mutation carriers with and without clinically overt hypertrophic cardiomyopathy.

In hypertrophic cardiomyopathy (HC), electrocardiographic (ECG) changes have been postulated to be an early marker of disease, detectable in sarcomere mutation carriers when left ventricular (LV) wall thickness is still normal. However, the ECG features of mutation carriers have not been fully characterized. Therefore, we systematically analyzed ECGs in a genotyped HC population to characterize ECG findings in mutation carriers (G+) with and without echocardiographic LV hypertrophy (LVH), and to evaluate the accuracy of ECG findings to differentiate at-risk mutation carriers from genetically unaffected relatives during family screening. The ECG and echocardiographic findings were analyzed from 213 genotyped subjects (76 G+/LVH-, 57 G+/LVH+ overt HC, 80 genetically unaffected controls). Cardiac magnetic resonance imaging was available on a subset. Q waves and repolarization abnormalities (QST) were highly specific (98% specificity) markers for LVH- mutation carriers, present in 25% of G+/LVH- subjects, and 3% of controls (p <0.001). QST ECG abnormalities remained independently predictive of carrying a sarcomere mutation after adjusting for age and impaired relaxation, another distinguishing feature of G+/LVH- subjects (odds ratio 8.4, p = 0.007). Myocardial scar or perfusion abnormalities were not detected on cardiac magnetic resonance imaging in G+/LVH- subjects, irrespective of the ECG features. In overt HC, 75% had Q waves and/or repolarization changes, but <25% demonstrated common isolated voltage criteria for LVH. In conclusion, Q waves and repolarization abnormalities are the most discriminating ECG features of sarcomere mutation carriers with and without LVH. However, owing to the limited sensitivity of ECG and echocardiographic screening, genetic testing is required to definitively identify at-risk family members.

Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy.

BACKGROUND: Genetic testing identifies sarcomere mutation carriers (G+) before clinical diagnosis of hypertrophic cardiomyopathy (HCM), allowing characterization of initial disease manifestations. Previous studies demonstrated that impaired relaxation develops before left ventricular hypertrophy (LVH). The precise impact of sarcomere mutations on systolic function in early and late disease is unclear. METHODS AND RESULTS: Comprehensive echocardiography with strain imaging was performed on 146 genotyped individuals with mutations in 5 sarcomere genes. Contractile parameters were compared in 68 preclinical (G+/LVH-), 40 overt (G+/LVH+) subjects with HCM, and 38 mutation (-) normal control relatives. All subjects had normal left ventricular ejection fraction. In preclinical HCM, global and regional peak systolic strain (epsilon(sys)) and longitudinal systolic strain rate were not significantly different from controls, but early diastolic mitral annular velocity (Ea) was reduced by 13%. In overt HCM, there was a significant 27% and 14% decrease in global longitudinal epsilon(sys) and systolic strain rate, respectively, compared with both preclinical HCM and controls (P<0.013 for all comparisons), and a 33% reduction in Ea. CONCLUSIONS: Sarcomere mutations have disparate initial effects on diastolic and systolic functions. Preclinical HCM is characterized by impaired relaxation but preserved systolic strain. In contrast, both diastolic and longitudinal systolic abnormalities are present in overt disease despite normal ejection fraction. We propose that diastolic dysfunction is an early consequence of sarcomere mutations, whereas systolic dysfunction results from mutations combined with subsequent pathological remodeling. Identifying mechanistic pathways triggered by these mutations may begin to reshape the clinical paradigm for treatment, based on early diagnosis and disease prevention.

Different prognostic impact of systolic function in patients with heart failure and/or acute myocardial infarction.

AIMS: To study the prognostic importance of left ventricular systolic function in patients with heart failure (HF) and acute myocardial infarction (AMI) with respect to the presence of prior heart failure and known ischemic heart disease. METHODS: In 13,084 consecutive patients diagnosed with either AMI or HF, a medical history and an echocardiographic assessment of left ventricular systolic function by wall motion index (WMI) were obtained. Patients were divided into four groups: AMI with or without a history of HF, and primary HF (no recent AMI) with or without a history of ischemic heart disease (IHD). Mortality was assessed after nine years of follow-up. RESULTS: WMI stratified patients according to all-cause mortality in all four groups of patients (p<0.0001). For a decrease in WMI of 0.3 (corresponding to a decrease in left ventricular ejection fraction of 0.1), the hazard ratio was 1.61 (95% CI: 1.48-1.76) for AMI patients without prior HF, 1.43 (1.38-1.48) for AMI patients with prior HF, 1.26 (1.22-1.30) for primary HF patients with IHD and 1.23 (1.18-1.27) for HF patients without IHD. CONCLUSION: WMI stratifies patients with IHD and/or HF according to risk of all-cause death. The presence of HF attenuates the prognostic power of WMI.