Natriuretic peptides and soluble ST2 improves echocardiographic diagnosis of elevated left ventricular filling pressures.

Elevated filling pressure of the left ventricle (LV) defines diastolic dysfunction. The gold standard for diagnosis is represented by the measurement of LV end-diastolic pressure (LVEDP) during cardiac catheterization, but it has the disadvantage of being an invasive procedure. This study aimed to investigate the correlation between LVEDP and cardiac serum biomarkers such as natriuretic peptides (mid-regional pro-atrial natriuretic peptide [MR-proANP], B-type natriuretic peptide [BNP], and N-terminal prohormone BNP [NT-proBNP]), soluble ST2 (sST2), galectin-3 and mid-regional pro-adrenomedullin (MR-proAMD). Consecutive patients hospitalized in a tertiary center and undergoing left cardiac catheterization were included in the study. Diastolic dysfunction was considered present if the end-expiratory LVEDP was ≥ 15 mmHg. Cardiac biomarkers were determined from pre-procedural peripheral venous blood samples. A total of 110 patients were included, of whom 76 (69.0%) were males, with a median age of 65 (55-71) years. Median LVEDP was 13.5 (8-19) mmHg and diastolic dysfunction was present in 50 (45.4%) of the patients. LVEDP correlated with BNP (p < 0.0001, r = 0.39 [0.20-0.53]), NT-proBNP (p < 0.0001, r = 0.40 [0.22-0.55]), MR-proANP (p = 0.001, r = 0.30 [0.11-0.46]), sST2 (p < 0.0001, r = 0.47 [0.30-0.60]), but not with MR-proAMD (p = 0.77) or galectin-3 (p = 0.76). In the final stepwise multivariable binary logistic regression model, diastolic dysfunction was predicted by NT-proBNP, mitral average E/e', sST2, atrial fibrillation, and left atrium reservoir strain. BNP, NT-proBNP, MR-proANP, and sST2 had predictive value for diastolic dysfunction. In contrast, galectin-3 and MR-proAMD were not associated with increased filling pressures. Furthermore, NT-proBNP and sST2 significantly improved diastolic dysfunction prediction in the final multivariable model.

Emerging Biomarkers for Predicting Clinical Outcomes in Patients with Heart Disease.

Cardiovascular disease is most frequently caused by the development and progression of atherosclerosis. When coronary arteries are afflicted, and the stenoses caused by atherosclerotic plaques are severe enough, the metabolic supply-and-offer balance is disturbed, leading to myocardial ischemia. If atherosclerotic plaques become unstable and local thrombosis develops, a myocardial infarction occurs. Sometimes, myocardial ischemia and infarction may result in significant and irreversible heart failure. To prevent severe complications, such as acute coronary syndromes and ischemia-related heart failure, extensive efforts have been made for developing biomarkers that would help identify patients at increased risk for cardiovascular events. In this two-part study, we attempted to provide a review of existing knowledge of blood biomarkers that may be used in this setting. The first part of this work was dedicated to conventional biomarkers, which are already used in clinical practice. In the second part, here presented, we discuss emerging biomarkers which have not yet become mainstream.

Conventional Biomarkers for Predicting Clinical Outcomes in Patients with Heart Disease.

Atherosclerosis is the main cause of cardiovascular disease worldwide. The progression of coronary atherosclerosis leads to coronary artery disease, with impaired blood flow to the myocardium and subsequent development of myocardial ischemia. Acute coronary syndromes and post-myocardial infarction heart failure are two of the most common complications of coronary artery disease and are associated with worse outcomes. In order to improve the management of patients with coronary artery disease and avoid major cardiovascular events, several risk assessment tools have been developed. Blood and imaging biomarkers, as well as clinical risk scores, are now available and validated for clinical practice, but research continues. The purpose of the current paper is to provide a review of recent findings regarding the use of humoral biomarkers for risk assessment in patients with heart disease.

Loeffler Endocarditis Causing Heart Failure with Preserved Ejection Fraction (HFpEF): Characteristic Images and Diagnostic Pathway.

We report the case of a 69-year-old female patient in which echocardiography and cardiac magnetic resonance imaging were used to diagnose a patient presenting with heart failure with preserved ejection fraction (HFpEF) due to Loeffler endocarditis. Loeffler endocarditis is an uncommon cause of heart failure with preserved ejection fraction, triggered by eosinophil and lymphocyte infiltration of the endomyocardium, followed by the formation of thrombus in the afflicted area, and eventually fibrosis. This condition is due to an increased number of eosinophils associated with allergies, infections, systemic conditions, as well as malignancies and hypereosinophilic syndrome. Loeffler endocarditis can lead to serious complications, such as progressive heart failure, systemic thromboembolic events, or arrhythmias (including sudden cardiac death).

Renal dysfunction is associated with lower incidence of positive fractional flow reserve values in patients with severe hypertension.

BACKGROUND: Renal dysfunction, an important predictor of cardiovascular mortality, is paradoxically associated with a lower incidence of positive coronary fractional flow reserve (FFR) values, possibly due to renal disease-associated myocardial microvascular dysfunction. It is unknown if this relationship is influenced by arterial hypertension, a condition strongly associated with renal- and microvascular dysfunction. METHODS: The incidence of positive (<0.81) FFR values was retrospectively evaluated in consecutive patients with intermediate severity coronary artery lesions that were either associating or not associating renal dysfunction (creatinine clearance, CrCl <90 mL/min/1.73 m2), and had mild/moderate or severe arterial hypertension (treated by <3 or ≥3 different drugs). RESULTS: Positive FFR values were found in 49.5% of the 109 included patients, with a significantly lower incidence in those with renal dysfunction: 23 vs. 31 cases (39.7% vs. 60.8%, P=0.03). However, uni- and multivariate subpopulation analysis evidenced that renal dysfunction was a significant independent predictor of fewer positive FFR results only in severely hypertensive patients (univariate P values for mild/moderate and severe hypertension: 0.80 and <0.01, respectively; multivariate P in severely hypertensive patients: 0.04). This categorization significantly restricted the number of borderline FFR results (0.75-0.80) where measurement interpretation could be challenging because of renal dysfunction (from 13.8% to 4.6% of the whole study population, P=0.03). CONCLUSIONS: In the current study renal dysfunction was independently associated with a significantly higher incidence of negative FFR results in patients with intermediate severity coronary artery lesions only in the presence of severe arterial hypertension. This observation should be confirmed by large-scale prospective clinical trials.

Incremental Predictive Value of Longitudinal Axis Strain and Late Gadolinium Enhancement Using Standard CMR Imaging in Patients with Aortic Stenosis.

To analyse the predictive ability and incremental value of left ventricular longitudinal axis strain (LAS) and late gadolinium enhancement (LGE) using standard cardiovascular magnetic resonance (CMR) imaging for the diagnosis and prognosis of severe aortic stenosis (AS) in patients with an indication for aortic valve replacement. We conducted a prospective study on 52 patients with severe AS and 52 volunteers. The evaluation protocol included standard biochemistry tests, novel biomarkers of myocardial fibrosis, 12-lead electrocardiograms and 24-hour Holter, the 6-minute walk test and extensive echocardiographic and CMR imaging studies. Outcomes were defined as the composite of major cardiovascular events (MACEs). Among AS patients, most (n = 17, 77.2%) of those who exhibited LGE at CMR imaging had MACEs during follow-up. Kaplan⁻Meier curves for event-free survival showed a significantly higher rate of MACEs in patients with LGE (p < 0.01) and decreased LAS (p < 0.001). In Cox regression analysis, only reduced LAS (hazard ratio 1.33, 95% CI (1.01 to 1.74), p < 0.01) and the presence of LGE (hazard ratio 11.3, 95% CI (1.82 to 70.0), p < 0.01) were independent predictors for MACEs. The predictive value increased if both LGE and reduced LAS were added to left ventricular ejection fraction (LVEF). None of the biomarkers of increased collagen turnover exhibited any predictive value for MACEs. LAS by CMR is an independent predictor of outcomes in patients with AS and provides incremental value beyond the assessment of LVEF and the presence of LGE.

Changes in left atrial size and function early after cardiac resynchronization therapy as assessed by conventional two-dimensional echocardiography.

AIMS: Cardiac resynchronization therapy (CRT) was shown to improve left atrial (LA) size and function within months after the procedure. We aimed to assess the impact of CRT on left atrial (LA) size and function within days after the procedure. Materials and methods: Twenty-eight consecutive patients with CRT were evaluated before the procedure and within 3 days afterwards, and 25 of them were also examined at three months. Echocardiography was performed to assess LA size and function: LA volumes indexed to body surface (LAVIs) were measured at different moments during the cardiac cycle: ventricular end-systole - maximum LAVI (LAVImax), before atrial systole (LAVIpreA), and at ventricular end-diastole - minimum LAVI (LAVImin). These measurements were further used to calculate LA function parameters: LA total emptying fraction, activeemptying fraction and passive emptying fraction. RESULTS: LAVImax decreased within days after the procedure - 45.5 mL/ m2 (38.2-56.7) vs. 42.9 mL/m2 (32.1- 56.2), p <0.05, as did LAVImin - 27.1 mL/m2 (22.9-41.9) vs. 25.9 mL/m2 (17.8-38.1), p <0.05, and LAVIpreA - 40.0 mL/m2 (31.3-53.0) vs. 35.5 mL/m2 (25.8-49.1), without significant changes in functional parameters. All LAVIs were correlated to the diastolic filling time/RR interval ratio after CRT, but not before. CONCLUSIONS: LAVIs may be reduced within days after the implant procedure in responders to CRT, while atrial functional parameters remain unchanged. Correlations beween LAVIs and the diastolic filling time/RR interval ratio after CRT suggest that early optimization of atrio-ventricular and ventriculo-ventricular delays may have a positive and immediate impact on LA size.

Pulmonary Artery Stiffness by Cardiac Magnetic Resonance Imaging Predicts Major Adverse Cardiovascular Events in patients with Chronic Obstructive Pulmonary Disease.

In this prospective pilot study, we aimed to evaluate the ability of cardiac magnetic resonance imaging (CMR) parameters of right ventricular function and pulmonary artery stiffness to identify pulmonary hypertension (PH), predict major adverse cardiovascular events (MACEs) in patients with secondary PH due to chronic obstructive pulmonary disease (COPD), and to estimate a prospective sample size necessary for a reliable power of the study. Thirty consecutive patients with COPD and suspected secondary PH were assessed by clinical examination, the six minute walk test, echocardiography, right heart catheterization and CMR, and followed-up for a mean period of 16 months to identify MACEs (cardiac death, ventricular tachyarrhythmia, and heart failure). Among CMR parameters of pulmonary artery stiffness, pulse wave velocity (PWV) yielded the best sensitivity (93.5%) and specificity (92.8%) for identifying PH, as diagnosed by cardiac catheterization. Moreover, PWV proved to be a valuable predictor of MACEs (HR = 4.75, 95% CI 1.00 to 22.59, p = 0.03). In conclusion, PWV by phase-contrast CMR can accurately identify PH in patients with COPD and may help stratify prognosis.

The value of global longitudinal strain and galectin-3 for predicting cardiovascular events in patients with severe aortic stenosis.

AIMS: Left ventricular global longitudinal strain (GLS) was shown to predict outcomes after valve replacement in patients with aortic stenosis (AS). In the current study, we aimed to test the combined use of GLS and a marker of fibrosis - Galectin-3 - for predicting major cardiovascular adverse events (MACEs) in patients with severe AS. MATERIALS AND METHODS: We conducted a prospective study on 42 patients with severe AS and 42 volunteers. Patient evaluation included biochemistry tests, electrocardiogram, 24-hour Holter monitoring, the 6-minute walk test, and echocardiography. Outcomes of AS patients were defined as the composite of MACEs - sudden cardiac death, non-fatal myocardial infarction, sustained ventricular arrhythmias,atrial arrhythmias, and hospitalization for heart failure. RESULTS: Patients with severe AS had lower GLS, and increased levels of both biomarkers compared to the control group. Both biomarkers correlated to echocardiographic parameters such as left ventricular (LV) mass index, relative wall thickness, GLS, as well as with the 6-minute walk test distance, and glomerular filtration rate (eGFR). GLS and NT-proBNP predicted MACEs reasonably well, while Galectin-3 did not, after adjustments for confounding factors. Kaplan-Meier analysis showed that the probability of freedom from MACEs was significant in patients who exhibited lower GLS [HR 2.73 (95% CI 1.01-7.53), p<0.05] and higher levels of NT-proBNP [HR 5.22 (95% CI 1.85- 14.51), p=0.001]. CONCLUSIONS: Among tested parameters, GLS and NT-proBNP were the most reliable predictors of MACEs in patients with severe AS, while Galectin-3 performed more poorly.

Correlations between echocardiographic parameters of right ventricular dysfunction and Galectin-3 in patients with chronic obstructive pulmonary disease and pulmonary hypertension.

AIM: To evaluate the association between echocardiographic right ventricular (RV) structural and functional parameters and galectin-3 levels in patients with chronic obstructive pulmonary disease (COPD) and associated pulmonary hypertension presenting with acutely aggravated dyspnoea. MATERIAL AND METHODS: We conducted a prospective study on forty patients with COPD and forty healthy volunteers matched for age and sex (mean age 59+/-6 years), measuring galectin-3 and NT-proBNP serum levels and specific echocardiographic parameters. RESULTS: Galectin-3 was significantly higher in patients with COPD and elevated systolic pulmonary artery pressure than in healthy volunteers and discriminated better between patients with likely and possible pulmonary hypertension when compared to NT-proBNP. In multivariate analysis, the global model was better related to galectin-3 than to NT-proBNP levels (R²=0.61 vs. 0.31, p<0.001). Moreover, in contrast to NT-proBNP levels, correlations between galectin-3 levels and RV dysfunction, as assessed by the E/E' ratio and RV ejection fraction, persisted after adjustment for cardiovascular risk factors and COPD-induced inflammation. CONCLUSION: In patients with COPD-associated pulmonary hypertension presenting with acutely aggravated dyspnoea, galectin-3 levels are predictive of RV dysfunction and correlate better with RV dysfunction parameters compared to NT-proBNP.

Clinical utility of echocardiography and magnetic resonance imaging for detecting cardiac complications in systemic sclerosis. A case report.

Systemic sclerosis (SSc) is a chronic autoimmune disease that beside the skin involvement it may affect the peripheral vessels and several organs, such as the lungs, the kidneys or the heart. Cardiac impairment usually becomes symptomatic in the late stages of the disease and is associated with poor prognosis. We report the case of a 80-year-old woman patient presenting symptoms of heart failure, subsequently diagnosed with limited SSc. The cardiac function was evaluated using a combined approach based on echocardiography, cardiac magnetic resonance imaging with late gadolinium enhancement. This case shows the fatal consequences of the late diagnosis of SSc.

Soluble ST2 in Ventricular Dysfunction.

Heart failure is a commonly encountered condition associated with increased morbidity, mortality, and healthcare cost. For years, its management has been strongly influenced by the use of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide biomarkers. In some cases, this approach does not always identify patients with heart failure accurately and may not provide the best prognostic assessment, particularly in the presence of comorbidities. Biomarkers that help refine diagnosis and risk stratification are needed. Soluble ST2, a peptide belonging to the interleukin-1 receptor family, is secreted when cardiomyocytes and cardiac fibroblasts are subjected to mechanical strain. Although preliminary results on this novel biomarker are encouraging, additional and more comprehensive studies are clearly needed to establish its role in the management of patients with heart failure. The purpose of this chapter is to provide an overview of data currently available.

Right Atrium Volume Index in Patients with Secondary Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease.

BACKGROUND: Right atrium volume index has recently been described as a quantitative and highly reproducible echocardiographic parameter associated with right ventricle systolic dysfunction in patients with chronic systolic heart failure. The aim of the current study was to assess right atrium remodeling and to establish correlations with echocardiographic parameters of right ventricle systolic and diastolic dysfunction in patients with pulmonary hypertension due to chronic obstructive pulmonary disease (COPD). METHODS: The study was conducted on 40 patients with secondary pulmonary hypertension due to COPD and 40 healthy volunteers (mean age 59 ± 6 years) who submitted to detailed echocardiographic examinations. Plasma levels of the soluble interleukin-1 receptor family member, N-terminal pro-B type natriuretic peptide and galectin-3 were measured in both groups. RESULTS: The right atrium volume index was significantly higher in the test group (45.7 ± 15.3 vs. 25.4 ± 4.0 mL/m(2)) and showed strong correlations to tricuspid annular plane systolic excursion (r = -0.733, p < 0.0001), right ventricle fractional area change (r = -0.662, p < 0.0001), right ventricle ejection fraction (r = -0.741, p < 0.0001), and systolic pulmonary artery pressures (r = 0.721, p < 0.0001). Multivariate analysis facilitated the construction of a linear regression model which showed that right ventricle systolic dysfunction parameters (R(2)-adjusted = 0.62, p < 0.001), elevated systolic pulmonary artery pressure (R(2)-adjusted = 0.52, p < 0.001) and heart failure biomarkers (log-transformed sST2, galectin-3 and N-terminal pro-B type natriuretic peptide) (R(2)-adjusted = 0.41, p < 0.001) were independently associated with right atrium volume index. CONCLUSIONS: Right ventricle systolic dysfunction and elevated systolic pulmonary artery pressure are independently associated with right atrium volume index in patients with pulmonary hypertension due to COPD. KEY WORDS: Echocardiography; Right atrium volume index; Right ventricular diastolic function; Right ventricular systolic function.

Serum levels of the soluble IL-1 receptor family member ST2 and right ventricular dysfunction.

AIMS: We aimed to assess the relationship between right ventricle (RV) dysfunction parameters and the soluble IL-1 receptor family member (sST2) in patients with secondary pulmonary hypertension owing tochronic obstructive pulmonary disease. MATERIALS & METHODS: A total of 36 patients with chronic obstructive pulmonary disease and secondary pulmonary hypertension (mean age: 59 ± 7 years) and 36 healthy volunteers (mean age: 59 ± 8 years) were enrolled in the study. sST2 and NT-proBNP levels, as well as specific echocardiographic parameters were measured. RESULTS: Both sST2 and NT-proBNP levels were greater in the test group. The sST2 levels were inversely associated with RV fractional area change(r = -0.762; p < 0.001), as well as with the RV ejection fraction (r = -0.799; p < 0.001), tricuspid annular plane systolic excursion (r = -0.773; p < 0.001) and increased pulmonary artery systolic pressure (r = 0.603;p < 0.001). Receiver operating characteristic curve analysis revealed that sST2 had lower sensitivity for identifying RV dysfunction when compared with NT-proBNP (71.4 vs 100%), despite having the same specificity (84%). CONCLUSION: The current study reveals correlations between sST2 levels and echocardiographic parameters of RV dysfunction, suggesting that use of sST2 and NT-proBNP may improve diagnosis and risk stratification in patients with secondary pulmonary hypertension owing to chronic obstructive pulmonary disease.

Left atrium function assessment by echocardiography - physiological and clinical implications.

Left atrium enlargement is a pathophysiological response to volume and pressure overload associated with a wide range of cardiovascular disorders leading to left ventricle systolic and diastolic dysfunction. Physiological factors contribute to significant differences in left atrium size in normal individuals. Moreover, left atrium enlargement was shown to have a significant prognostic value for cardiovascular events such as heart failure, atrial fibrillation or stroke, and increased cardiovascular and all-cause mortality rates. Current imaging techniques such as two- and three dimensional echocardiography, cardiac magnetic resonance imaging and multi-detector computed tomography allow a detailed assessment of the left atrium. The current paper aims to offer an overview of two-dimensional echocardiography parameters which provide data concerning left atrium dimensions and phasic functions and may lead to a better understanding of left atrium physiology and pathology.

Plasma homocysteine and the severity of heart failure in patients with previous myocardial infarction.

BACKGROUND: Homocysteine is considered to be a risk factor, or an indicator of risk, for the development of cardiovascular disease. Little data is available on its significance in patients with previous myocardial infarction. The aim of our study was to assess the plasma level of homocysteine and its relationship with the severity of heart failure in patients with chronic myocardial infarction. METHODS: We studied 144 patients with previous myocardial infarction. Patients were divided into two groups according to the presence or absence of heart failure, as certified by clinical evidence of heart failure and by echocardiographic criteria for left ventricular systolic dysfunction. RESULTS: Of the patients with prior myocardial infarction (144; 63.6 ± 9.6 years) included in the study, 65 had heart failure. The mean level of homocysteine was significantly higher in the heart failure group (18.9 mmol/L) than in the non-heart failure group (14.1 mmol/L; p ≤ 0.001). Our study demonstrated that there is a statistically significant correlation between homocysteine plasma levels and the severity of heart failure in patients with prior myocardial infarction. Homocysteine levels have proved to become higher with NYHA class progression. A significant cross-sectional correlation has been assessed between homocysteine and tissue Doppler echocardiography parameters. CONCLUSIONS: Increased plasma homocysteine levels independently correlate with the severity of heart failure in patients with chronic myocardial infarction. We suggest that homocysteine can be used in clinical practice as a valuable heart failure risk marker in patients with chronic myocardial infarction.

Right renal artery occlusion as a complication of fibromuscular dysplasia.

Renovascular hypertension is defined as elevated blood pressure levels due to the stenosis/ occlusion of the renal artery caused by fibromuscular dysplasia or atherosclerosis. We present the case of a 59-year old female patient with recently diagnosed arterial hypertension due to renal artery occlusion through intimal fibromuscular dysplasia. In this case, arterial blood pressure levels have not been controlled by maximum doses of antihypertensive drugs, used in association; rapid deterioration of the renal function, as well as important kidney damage, proven by imaging explorations, motivated the laparoscopic nephrectomy.

The association between homocysteine level and metabolic syndrome in patients of prior myocardial infarction.

UNLABELLED: Homocysteine is considered to be a risk factor for the development of cardiovascular disease. Several observations suggest that there might be links between hyperhomocysteinemia and insulin resistance, its clinical surrogate of metabolic syndrome. The aim of the present study is to determine whether the presence of the metabolic syndrome is associated with elevated levels of homocysteine in patients with prior myocardial infarction. METHODS: We studied 104 consecutive patients with prior myocardial infarction undergoing coronary angiography. Patients were divided into two groups according to the presence or absence of metabolic syndrome, as certified by Adult Treatment Panel III. The dosage of homocysteine was measured by high performance liquid chromatography. The relationship between homocysteine levels and metabolic syndrome was assessed by multivariable regressions after adjustment on the basis of recognized predictive factors: age and sex. RESULTS: Out of a total numbers of patients with myocardial infarction (104; 63.6 +/- 9.2 years of age, 45.1% males) taken in study, 32 (30.1%) had metabolic syndrome. The mean level of homocysteine was significantly higher in the metabolic syndrome group (14.8 micromol/L) than in the free metabolic syndrome group (17.9 micromol/L) (p < or = 0.001). We found a positive correlation between plasma homocysteine levels and metabolic syndrome parameters. CONCLUSION: Elevated homocysteine levels were correlated to the metabolic syndrome in patients with prior myocardial infarction. These data indicate that elevated plasma homocysteine levels are not a risk factor for cardiovascular events in metabolic syndrome patients in contrast to patients without the metabolic syndrome.