Clinical Relevance of the Spectral Tissue Doppler E/e' Ratio in the Management of Patients with Atrial Fibrillation: a Comprehensive Review of the Literature.

Atrial fibrillation is the most common cardiac rhythm disorder observed in clinical practice. It carries high morbidity and mortality rates, primarily related to heart failure, stroke and death. Validation of noninvasive markers in the diagnosis of heart failure with preserved ejection fraction and risk stratification is relevant in this clinical setting. The spectral tissue Dopplerderived E/e' ratio is a simple and reproducible index, which has been validated in noninvasive assessment of left ventricular diastolic pressures, regardless of rhythm. Septal E/e' >11 is a good predictor of invasively determined left ventricular diastolic pressure >15 mmHg in patients with atrial fibrillation. Several studies have validated the clinical relevance of abnormal values for E/e' at rest and during exercise in the diagnosis and risk stratification of heart failure with preserved ejection fraction in patients with atrial fibrillation. Increased E/e' value is associated with adverse outcome (death, left atrial appendage thrombus, stroke and heart failure) in patients with atrial fibrillation and predicts arrhythmia recurrence after cardioversion and catheter ablation. In conclusion, E/e' by spectral tissue Doppler is clinically relevant in the clinical management of any patients with atrial fibrillation referred for transthoracic Doppler echocardiography.

Human serum albumin in cardiovascular diseases.

Cardiovascular diseases are the leading cause of death worldwide. Endothelial dysfunction, inflammation and oxidative stress are at the forefront in the onset and development of atherosclerosis and many cardiovascular diseases. Epidemiological evidence is that low serum albumin levels are linked to incident ischemic heart disease, heart failure, atrial fibrillation, stroke and venous thromboembolism, independent of risk factors, body mass index and inflammation. Hypoalbuminemia has also emerged as an independent prognosticator in many cardiovascular diseases, such as coronary artery disease, heart failure, congenital heart disease, infective endocarditis and stroke, even after adjusting for usual causal factors and prognostic markers. Given physiological properties of serum albumin that include anti-inflammatory, antioxidant, anticoagulant and antiplatelet aggregation activity as well as colloid osmotic effect, hypoalbuminemia could act as an unrecognized modifiable risk factor. The purpose of this review is to provide an overview of the physiological properties of serum albumin, as well as prevalence, causes, prognostic value and potential contribution to the disease emergence and progression of hypoalbuminemia, and the resulting clinical implications.

Prevalence and characteristics of coronary artery disease in heart failure with preserved and mid-range ejection fractions: A systematic angiography approach.

BACKGROUND: Guidelines recommend careful screening and treatment of coronary artery disease (CAD) in heart failure with preserved or mid-range ejection fraction (HFpEF/HFmEF). AIM: We aimed to determine the prevalence and characteristics of CAD using a prospective systematic coronary angiography approach. METHODS: A systematic coronary angiography protocol was applied in consecutive patients admitted for HFpEF/HFmEF during a 6-month period in a single centre. History of CAD and results of angiography, including revascularization, were reported. RESULTS: Of the 164 patients with HFpEF/HFmEF who were included, an angiography assessment was applied in 108 (66%) (median age: 79 years [interquartile range: 70-85 years]; 54% were women). In our analysis, 64% (95% confidence interval [CI] 55-73%) of patients had a significant coronary stenosis corresponding to a global CAD prevalence of 80% (95% CI 73-88%). The prevalence of CAD was similar for HFpEF and HFmEF. The left main coronary artery presented a significant stenosis in 6.5% of cases and 39% of patients had a two- or three-vessel disease. The rate of significant coronary stenosis was non-significantly higher in patients with a history of CAD. Patients with HFpEF/HFmEF with and without CAD did not differ in clinically meaningful ways, in terms of symptoms or laboratory and echocardiography results. This strategy led to complete revascularization in 36% of patients with significant stenosis and in 23% of all patients with HFpEF/HFmEF. CONCLUSIONS: Our study differs from others in that we used a systematic angiography approach. The results suggest a much higher prevalence of CAD in HFpEF/HFmEF than previously reported and should encourage clinicians to aggressively identify this co-morbidity.

Usefulness of serum albumin and serum total cholesterol in the prediction of hospital death in older patients with severe, acute heart failure.

BACKGROUND: Acute heart failure (HF) carries high hospital mortality rates in older patients; a multimarker strategy may help identify patients at high risk. AIMS: To investigate prospectively the prognostic relevance of serum albumin and serum total cholesterol (TC) in older patients with severe, acute HF. METHODS: Usual prognostic variables were collected on admission in 207 consecutive patients aged>70 years with severe, acute HF. Serum albumin and serum TC were obtained soon after clinical improvement. RESULTS: Hospital mortality rate was 19%. Patients who died were similar to patients who survived in terms of age, sex, heart rate, serum haemoglobin and left ventricular ejection fraction. Patients who died had higher concentrations of B-type natriuretic peptide (BNP), blood urea nitrogen, serum creatinine, C-reactive protein and serum troponin I, lower systolic blood pressure, and lower concentrations of serum albumin and serum TC than patients who survived (P<0.01 for all). Serum albumin was the best independent predictor of hospital death (odds ratio 0.82 [0.74-0.90], P<0.001), with blood urea nitrogen (P=0.02) and log (BNP) (P=0.02). A simple risk score based on serum albumin (<3g/dL; 2 points), BNP (>840pg/mL; 1 point) and blood urea nitrogen (>15.3mmol/L; 1 point) discriminated patients without (score 0 to 1, hospital death 4%) from patients with (score 2 to 4, hospital death 35%, P<0.001) a high risk of death. CONCLUSION: Hypoalbuminaemia offers powerful additional prognostic information to usual prognostic variables in older patients with severe, acute HF, and deserves further attention in multimarker strategies.

Human serum albumin in the clinical syndrome of heart failure.

Hypoalbuminemia is common in patients with heart failure, and this condition becomes more prevalent with increasing age and illness. Hypoalbuminemia is thought to result mainly from malnutrition, inflammation and cachexia. Other causal factors include hemodilution, liver dysfunction, protein-losing enteropathy, increased transcapillary escape rate, and nephrotic syndrome. According to Starling's law, low plasma oncotic pressure related to hypoalbuminemia induces a fluid shift from the intravascular to the interstitial space, and there is now clinical evidence that hypoalbuminemia facilitates the onset of cardiogenic pulmonary edema. Hypoalbuminemia has emerged as an independent predictor of incident heart failure in end-stage renal disease and elderly patients. Recent data also suggest that hypoalbuminemia provides prognostic information incremental to the usual clinical and biochemical variables in patients with heart failure regardless of clinical presentation. The presence of hypoalbuminemia in patients with heart failure may have potential therapeutic consequence in clinical practice. If present, subclinical excess of fluid must be removed. A dietary survey should also be performed, and renutrition may be indicated. It is unknown whether targeted nutritional intervention and albumin administration confer benefits to hypoalbuminemic patients with heart failure, and further research is warranted in this setting.

Clopidogrel loading dose adjustment according to platelet reactivity monitoring in patients carrying the 2C19*2 loss of function polymorphism.

OBJECTIVES: We aimed to investigate the biological impact of a tailored clopidogrel loading dose (LD) according to platelet reactivity monitoring in carriers of the cytochrome (CYP) 2C19*2 loss-of-function polymorphism undergoing percutaneous coronary intervention for an acute coronary syndromes. BACKGROUND: CYP2C19*2 polymorphism is associated with reduced clopidogrel metabolism and a worse prognosis after percutaneous coronary intervention. METHOD: A prospective multicenter study enrolling 411 patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention was performed. Platelet reactivity was measured using the vasodilator-stimulated phosphoprotein (VASP) index, and a cutoff value of ≥ 50% was used to define high on-treatment platelet reactivity (HTPR). The genetic polymorphism of CYP2C19 was determined by allele-specific polymerase chain reaction. In patients carrying CYP2C19*2 and exhibiting HTPR after a first 600-mg LD of clopidogrel, dose adjustment was performed by using up to 3 additional 600 mg LDs to obtain a VASP index <50%. RESULTS: One hundred thirty-four patients (35.3%) carried at least one 2C19*2 allele (11 homozygotes [2.7%] and 123 heterozygotes [32.6%]). The VASP index in these patients was significantly higher than in homozygotic patients for the wild-type alleles (61.7 ± 18.4% vs. 49.2 ± 24.2%; p < 0.001). Of the 134 carriers of the loss-of-function polymorphism, 103 were considered to have HTPR. After a second clopidogrel LD, the VASP index was significantly decreased in these patients (69.7 ± 10.1% vs. 50.6 ± 17.6%; p < 0.0001). Finally, dose adjustment according to platelet reactivity monitoring, enabled 88% of 2C19*2 carriers exhibiting HTPR to reach a VASP index <50%. CONCLUSIONS: Increased and tailored clopidogrel loading dose according to platelet reactivity monitoring overcome HTPR in carriers of the loss-of-function CYP2C19*2 polymorphism.

Intra-individual variability in clopidogrel responsiveness in coronary artery disease patients under long term therapy.

Clopidogrel responsiveness (CR) following a loading dose (LD) predicts thrombotic events after percutaneous coronary interventions (PCI). Some of the mechanisms involved in large inter-individual variability in CR may be varied. We therefore postulated that there may be an intra-individual variability in CR. Two hundred and one patients receiving long-term therapy with aspirin and clopidogrel after drug-eluting stents PCI were prospectively included in this monocentre study along with any patient re-admitted within 12 months post-PCI. Platelet reactivity (PR) inhibition was assessed by the vasodilator phosphoprotein (VASP) index following a 600 mg loading dose of clopidogrel on each admission to determine CR (VASP 1 during the first admission and VASP 2 during re-admission). DeltaVASP = VASP 2 –VASP 1 was used to study intra-individual variability in CR. We observed that the response to a 600 mg LD of clopidogrel was poorly correlated within an individual (kappa = 0.33; p < 0.001 (n = 201)). Although most patients had increased platelet inhibition at the time of readmission, 35.3% of patients exhibited a decreased platelet inhibition despite chronic clopidogrel therapy and a 600 mg reload. Quartiles analysis of DeltaVASP demonstrated that insulin-treated diabetes was associated with decreased CR over time (p = 0.03). In addition to the large inter-individual variability in clopidogrel responsiveness, there is large intra-individual variability. Decreased clopidogrel responsiveness despite long-term clopidogrel therapy could be a trigger for recurrent thrombotic events.

Accuracy of Doppler-derived pulmonary artery hypertension to predict heart failure with normal ejection fraction.

Recent advances have highlighted the clinical relevance of pulmonary artery hypertension in terms of diagnosis and prognosis in heart failure with normal ejection fraction. We addressed the usefulness of Doppler-derived pulmonary artery systolic pressure to predict heart failure with normal ejection fraction in stable patients with exertional dyspnea. 25 patients referred for clinically indicated catheterism with evidence of heart failure according to the European diagnostic flowchart on "how to diagnose heart failure with normal ejection fraction" and 12 controls referred for clinically indicated catheterism without this condition according to the diagnostic flowchart on "how to exclude heart failure with normal ejection fraction" were included. None of the patients presented with Doppler-derived pulmonary vascular resistance >2.5 WU. By logistic regression analysis, pulmonary artery systolic pressure predicted heart failure with normal ejection fraction (p=0.006), with an optimal cut-off value of 35 mmHg (area under the ROC curve of 0.80 [0.64-0.92], p<0.001; sensitivity 76%, specificity 75%). Positive and negative predictive values were 93 and 50% for the cut-off value of 40 mmHg. Doppler-derived pulmonary artery hypertension is a landmark of heart failure with normal ejection fraction in patients without severely increased pulmonary vascular resistance and deserves further attention in upcoming international recommendations.

Predictors of B-type natriuretic peptide and left atrial volume index in patients with preserved left ventricular systolic function: an echocardiographic-catheterization study.

BACKGROUND: B-type natriuretic peptide (BNP) and left atrial volume index (LAVi) are used as surrogate measures for global myocardial function and are recommended for the diagnosis of heart failure with normal ejection fraction. Little is known, however, about predictors in patients with preserved systolic function. AIMS: To identify factors that influence the relation of BNP and left atrial size to invasively determined left ventricular end-diastolic pressure in stable patients with preserved left ventricular systolic function. METHODS: Fifty-nine consecutive patients were included prospectively. Clinical, biological, Doppler echocardiographic and invasive variables were collected simultaneously. RESULTS: BNP was predicted independently by left ventricular ejection fraction, diastolic function and age (p<0.05). LAVi was predicted independently by left ventricular mass index and invasive left ventricular end-diastolic pressure (p<0.01). BNP predicted increased left ventricular end-diastolic pressure greater than 16 mmHg (p=0.004); the optimal cut-off value was 33 pg/mL (area under the receiver-operating characteristic curve [AUC] 0.74 [0.6-0.84], p<0.001, sensitivity 72%, specificity 70%). LAVi predicted increased left ventricular end-diastolic pressure (p<0.001); the optimal cut-off value for LAVi was 26 mL/m(2) (AUC 0.87 [0.75-0.94], p<0.001; sensitivity 85%, specificity 80%). Unlike BNP (p=0.1), LAVi performed well in patients with abnormal relaxation at mitral filling (p<0.01). CONCLUSION: BNP is influenced by age in stable patients with preserved systolic function and should be interpreted cautiously. LAVi is a powerful surrogate for invasively determined left ventricular end-diastolic pressure regardless of age and mitral filling.

Impact of P2Y12-ADP receptor polymorphism on the efficacy of clopidogrel dose-adjustment according to platelet reactivity monitoring in coronary artery disease patients.

INTRODUCTION: High on-treatment platelet reactivity (HTPR) after clopidogrel loading dose (LD) is associated with a high risk of thrombotic events after percutaneous coronary intervention(PCI). We have demonstrated that HTPR could be overcome in the majority of cases using LD adjustment resulting in an improved clinical outcome. However this strategy failed in nearly 10% of patients with HTPR. We aimed to determine if P2Y12-ADP receptor polymorphisms were associated with failed dose adjustment. MATERIAL AND METHOD: Forty-three patients undergoing PCI were included in this prospective study. A VASP index >or=50% after a 600 mg LD of clopidogrel defined HTPR. Dose adjustment was performed according to PR monitoring to reach a VASP index <50%. Genetic polymorphism of the P2Y12-ADP receptor was determined by direct sequencing. RESULTS: Patients with successful dose-adjustment (SDA) (n=33) and failed (FDA) (n=10) dose-adjustment groups were compared. The 2 groups were similar in terms of cardiovascular risk factors including diabetes mellitus (SDA vs FDA: 42 vs 20%; p=0.3). The prevalence of the H2 allele of the P2Y12-ADP receptor was also similar between the 2 groups (p=0.3). The H2 allele was found in 6 patients which are all included in the SDA group. After the first 600 mg loading dose of clopidogrel, patients carrying at least one H2 allele had similar VASP index compared to those carrying two copies of the wild type allele (H1) (SDA vs FDA: 44.9+/-14.9 vs 43.5+/-10%; p=0.8). CONCLUSION: The present study suggests that the H2 allele of the P2Y12-ADP receptor is not involved in clopidogrel failed dose adjustment according to platelet reactivity monitoring.

Usefulness of left atrial volume for the diagnosis of diastolic heart failure: an echocardiographic-catheterization study.

The present study attempted to determine the accuracy of left atrial volume (LAVi) by transthoracic echocardiography in the diagnosis of diastolic heart failure (DHF) in patients presenting with chronic, isolated dyspnea. We included 28 consecutive patients with a left ventricular ejection fraction >50% without prior history of heart failure. DHF was authenticated in 20 patients by invasive left ventricular end-diastolic pressure >16 mmHg. By logistic regression analysis, LAVi was predictive of DHF (p=0.015). LAVi>38 ml/m(2) was a useful predictor of DHF (area under the ROC curve of 0.84 [0.65-0.95], p<0.001, sensitivity 60%, specificity 100%). The standard cut-off value of 34 ml/m(2) was 70% sensitive and 88% specific.