2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).

Guidelines summarize and evaluate all available evidence on a particular issue at the time of the writing process, with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well as the risk-benefit ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.

Evaluation of aortic stenosis: an update--including low-flow States, myocardial mechanics, and stress testing.

Degenerative aortic stenosis (AS) is one of the most frequent valvular heart diseases in Western countries. Echocardiography plays a central role in the evaluation and management of patients with AS. To overcome the inherent inconsistencies between the echocardiographic parameters defining severe AS and to unify concepts, a new classification based on the interplay between flow and gradients has recently been adopted. Outcome studies of asymptomatic patients with preserved left ventricular ejection fraction (LVEF), as classified by this new approach, have shown that low-flow (LF) states are associated with poor outcome, that the classical normal-flow/high-gradient pattern has an intermediate outcome, while normal-flow/low-gradient severe AS seems to have an outcome comparable to moderate AS and such patients do not benefit from aortic valve replacement. Patients with LF/low-gradient severe AS with preserved LVEF, also known as "paradoxical LF/low-gradient AS," have the worst outcome and benefit greatly from surgical or percutaneous valve replacement, provided that severity is proven. In patients with LF/low-gradient and depressed LVEF, dobutamine stress echocardiography has an important role to distinguish severe from pseudo-severe AS and to assess surgical risk. Assessment of aortic valve calcium score, as well as computation of projected effective orifice aortic area at normal trans-valvular flow rates, has proved to be very useful to distinguish severe from pseudo-severe AS in LF/low-gradient AS with both reduced and preserved LVEF. Asymptomatic patients with normal flow/gradient should be submitted to an exercise test; exercise echocardiography can identify patients at increased risk when mean gradient increases by >18-20 mmHg and/or pulmonary arterial hypertension develops during exercise.

Left ventricular contractile reserve in asymptomatic primary mitral regurgitation.

AIMS: There are very few data regarding the assessment and prognostic value of left ventricular contractile reserve (LVCR) in asymptomatic patients with primary mitral regurgitation (MR). We aimed to quantify LVCR and to evaluate its usefulness for risk stratification in asymptomatic patients with primary MR. METHODS AND RESULTS: Comprehensive resting and exercise (EX) transthoracic echocardiography, including two-dimensional speckle tracking quantification, were performed in 115 consecutive asymptomatic patients with ≥ moderate degenerative MR and no LV dysfunction/dilatation. Left ventricular contractile reserve was defined as an EX-induced increase in LV ejection fraction (LVCR(LVEF)) ≥ 4% or in LV global longitudinal strain (LVCR(GLS)) ≥ 2%. LVCR(LVEF) was present in 54 patients (47%) and LVCR(GLS) in 58 (50%). The brain natriuretic peptide (BNP) level was significantly correlated with EX-induced changes in GLS (r = 0.45, P < 0.0001), but not in LVEF (r = 0.09, P = 0.31). Patients with no LVCR(GLS) had significant lower 3-year cardiac event-free survival (42 ± 8 vs. 69 ± 7%, P = 0.0008). In contrast, there was no significant difference in outcome regarding to the presence or absence of LVCR(LVEF) (60 ± 7 vs. 51 ± 8%, P = 0.40). The multivariable Cox proportional hazard model showed that the absence of LVCR(GLS) was a strong independent predictor of cardiac events (HR = 2.27, 95% CI: 1.05-4.76, P = 0.037), even after adjustment for Ex-echo variables and BNP level. The association between LVCR(GLS) and outcome remained significant (HR = 1.6, 95% CI: 1.1-2.3, P = 0.01) after further adjustment for the resting echocardiographic parameters included in the ESC Guidelines. CONCLUSION: In asymptomatic primary MR, LVCR seems to be better assessed using EX-induced changes in LV myocardial longitudinal function rather than in LVEF. In patients with preserved LV function, the absence of LVCR is independently associated with two-fold increase in risk of cardiac events. Left ventricular contractile reserve may be useful to improve risk stratification and clinical decision-making in these patients.

Active and total myeloperoxidase in coronary artery disease and relation to clinical instability.

OBJECTIVES: The aim of this study was to evaluate the correlation between serum total and active myeloperoxidase (MPO) levels and the presence of coronary artery disease in consecutive patients evaluated by coronary angiography and to correlate the levels of the enzyme with instability. METHODS AND RESULTS: Prospective analysis of serum samples of patients before coronary angiography. Total and active MPO concentrations were assessed by the sandwich Elisa and SIEFED® methods. Stable and unstable patients were separated into two groups. Differences between groups were analysed using the Student t test, chi square test or Fisher exact test, as appropriate. The relationship between total and active MPO was assessed using linear and curvilinear regression. Two hundred and twenty patients were included (age 66±11 years, 67% male) in the study. Among these, 62% presented significant coronary artery disease. Twenty-four patients (11%) presented unstable coronary syndrome. Mean active and total MPO levels in the population were 50.1±63.5 and 147.6±223.3 ng.mL(-1), respectively. In stable patients, mean active MPO was 47.1±47.9 ng.mL(-1) and in unstable patients 75.1±135.2 ng.mL(­1) (P=0.04). Mean total MPO was 146.3±224.7 ng.mL(-1) in the stable patients and 158.2±215.8 ng.mL(-1) in the unstable patients (P=0.8). Unstable patients had a significantly higher level of active MPO than stable patients but there was no significant difference between unstable and stable patients regarding total MPO. CONCLUSION: A correlation was observed between active MPO and clinical instability but not with total MPO. These results suggest that this marker could be a powerful indicator of instability and could have a prognostic impact.

Cardiovascular outcome in systemic sclerosis.

OBJECTIVES: Cardiovascular involvement is recognized as a poor prognostic factor in systemic sclerosis (SSc). The aim of this study was to evaluate the usefulness of nailfold video-capillaroscopy (NVC), brain natriuretic peptide (BNP) blood level and exercise echocardiography to predict the occurrence of cardiovascular events in SSc. METHODS: We prospectively enrolled 65 patients with SSc (age 54±14 years, 30% female) followed in CHU Sart-Tilman, Liège, Belgium. All patients underwent graded semi-supine exercise echocardiography. Both baseline resting pulmonary hypertension (PH) and PH during follow-up (FUPH) were defined as systolic pulmonary arterial pressure (sPAP)>35 mmHg, and exercise-induced PH (EIPH) as sPAP>50 mmHg during exercise. RESULTS: EIPH was present in 21 patients. During FU (27±18 months), 13 patients developed FUPH and 9 presented cardiovascular complications. Patients with cardiovascular events were significantly older (63±14 vs 52±13 years; P=0.03), presented more frequently NVC grade>2 (89 vs 43%; P=0.009), had higher resting and exercise sPAP (30±6 vs 24±6; P=0.007 and 57±13 vs 44±13 vs mmHg; P=0.01, respectively), and higher BNP blood level (112±106 vs 26±19 pg/ml; P=0.0001). After adjustment for age and gender, NVC grade>2 (ß=2.4±1.1; P=0.03), EIPH (ß=2.30±1.13; P=0.04), FUPH (ß=0.24±0.09; P=0.01 and ß=3.52±1.16; P=0.002, respectively;) and BNP (ß=0.08±0.04; P=0.02) were independent predictors of CV events. Beyond age, an incremental value of EIPH, BNP and NVC grade>2 was predictive of cardiovascular events (P<0.001). CONCLUSION: Cardiovascular complications are not rare in SSc (18%). NVC, BNP blood level assessment and exercise echocardiography could be useful tools to identify patients at risk of SSc.

Late gadolinium enhancement CMR in primary mitral regurgitation.

AIMS: The appropriate timing for surgery in severe asymptomatic primary mitral regurgitation (MR) remains controversial. It has been shown that late gadolinium enhancement on cardiovascular magnetic resonance (LGE CMR), which may identify myocardial fibrosis, is associated with a worse outcome in various cardiomyopathies. We sought to investigate the prevalence and significance of delayed enhancement in primary MR. METHODS: We prospectively included 41 patients with at least moderate primary MR and without overt signs of left ventricular (LV) dysfunction. Patients with evidence of coronary artery disease, arrhythmias or significant concomitant valvular disease were excluded. All patients were scheduled for transthoracic echocardiography and LGE CMR. RESULTS: A total of 39 patients had interpretable LGE CMR images. Among them, 12 (31%) had late contrast uptake of the LV wall. LGE CMR showed an infarct pattern in three patients, a pattern of mid-wall fibrosis in seven patients and two patients had a combined pattern. Patients with delayed enhancement on CMR had significant higher LV diameters (LV end-systolic diameter 39 ± 4 vs. 34 ± 5 mm, P = 0·002; LV end-diastolic diameter 57 ± 5 vs. 50 ± 5 mm, P = 0·001). There was a trend towards a higher indexed left atrial volume (55 ± 21 vs. 44 ± 13 mL/m², P = 0·06). By contrast, there was no significant association between myocardial contrast uptake and age, LV ejection fraction and MR severity. CONCLUSION: Left ventricular remodelling seems to be associated with the presence of delayed enhancement on CMR in primary MR. Further data are needed to determine whether LGE CMR can predict a less favourable outcome or could improve risk stratification in asymptomatic primary MR.

ESC Working Group on Valvular Heart Disease position paper--heart valve clinics: organization, structure, and experiences.

BACKGROUND: With an increasing prevalence of patients with valvular heart disease (VHD), a dedicated management approach is needed. The challenges encountered are manifold and include appropriate diagnosis and quantification of valve lesion, organization of adequate follow-up, and making the right management decisions, in particular with regard to the timing and choice of interventions. Data from the Euro Heart Survey have shown a substantial discrepancy between guidelines and clinical practice in the field of VHD and many patients are denied surgery despite having clear indications. The concept of heart valve clinics (HVCs) is increasingly recognized as the way to proceed. At the same time, very few centres have developed such expertise, indicating that specific recommendations for the initial development and subsequent operating requirements of an HVC are needed. AIMS: The aim of this position paper is to provide insights into the rationale, organization, structure, and expertise needed to establish and operate an HVC. Although the main goal is to improve the clinical management of patients with VHD, the impact of HVCs on education is of particular importance: larger patient volumes foster the required expertise among more senior physicians but are also fundamental for training new cardiologists, medical students, and nurses. Additional benefits arise from research opportunities resulting from such an organized structure and the delivery of standardized care protocols. CONCLUSION: The growing volume of patients with VHD, their changing characteristics, and the growing technological opportunities of refined diagnosis and treatment in addition to the potential dismal prognosis if overlooked mandate specialized evaluation and care by dedicated physicians working in a specialized environment that is called the HVC.

Determinants and prognostic significance of exercise pulmonary hypertension in asymptomatic severe aortic stenosis.

BACKGROUND: Recent studies emphasized the usefulness of exercise stress echocardiography in asymptomatic patients with aortic stenosis. Nevertheless, the additive value of exercise pulmonary hypertension (Ex-PHT) in such patients remains unexplored. We therefore aimed to identify the determinants and to test the impact on outcome of Ex-PHT in asymptomatic patients with severe aortic stenosis. METHOD AND RESULTS: Asymptomatic patients with severe aortic stenosis (n=105; aortic valve area <0.6 cm(2)/m(2); age, 71±9 years; male, 59%) and preserved left ventricular systolic function (ejection fraction ≥55%) were prospectively submitted to exercise stress echocardiography. Resting PHT and Ex-PHT were defined as a systolic pulmonary arterial pressure >50 and >60 mm Hg, respectively. Ex-PHT was more frequent than resting PHT (55% versus 6%; P<0.0001). On multivariable logistic regression, the independent predictors of Ex-PHT were male sex (odds ratio, 4.3; P=0.002), resting systolic pulmonary arterial pressure (odds ratio, 1.16; P=0.002), exercise indexed left ventricular end-diastolic volume (odds ratio, 1.04; P=0.026), exercise e'-wave velocity (odds ratio, 1.35; P=0.047), and exercise-induced changes in indexed left atrial area (odds ratio, 1.36; P=0.006). Ex-PHT was associated with reduced cardiac event-free survival (at 3 years, 22±7% versus 55±9%; P=0.014). In a multivariable Cox proportional hazards model, Ex-PHT was identified as an independent predictor of cardiac events (hazard ratio, 1.8; 95% confidence interval, 1.0-3.3; P=0.047). When exercise-induced changes in mean aortic pressure gradient were added to the multivariable model, Ex-PHT remained independently associated with reduced cardiac event-free survival (hazard ratio, 2.0; 95% confidence interval, 1.1-3.6; P=0.025). CONCLUSIONS: In asymptomatic patients with severe aortic stenosis, the main determinants of Ex-PHT are male sex, resting systolic pulmonary arterial pressure, and exercise parameters of diastolic burden. Moreover, Ex-PHT is associated with a 2-fold increased risk of cardiac events. These results strongly support the use of exercise stress echocardiography in asymptomatic aortic stenosis.

The role of stress testing in evaluation of asymptomatic patients with aortic stenosis.

PURPOSE OF REVIEW: The emerging role of exercise and especially exercise echocardiography in aortic stenosis has been recently emphasized. In this clinical setting, stress testing can help identify patients who are falsely asymptomatic, unmask those who will rapidly become symptomatic and appraise the true haemodynamic consequences of aortic stenosis. RECENT FINDINGS: Both exercise stress test and exercise stress echocardiography are strictly contraindicated in symptomatic patients. In contrast, exercise testing is recommended by current guidelines in asymptomatic patients with aortic stenosis. During exercise, either the development of symptoms or an abnormal blood pressure response is associated with a poor outcome and should be considered as an indication for surgery. Exercise echocardiography permits stratification and identification of asymptomatic patients at a higher risk of a cardiac event: exercise-induced increase of more than 18-20  mmHg in mean pressure gradient, absence of left ventricular contractile reserve and/or exercise pulmonary hypertension are suggestive features of an advanced disease process. SUMMARY: Exercise echocardiography has the advantage of its wide availability, low cost and versatility. In asymptomatic severe aortic stenosis, exercise echocardiography can help unmask patients at a more advanced stage of the disease and could aid in identifying those who may benefit from an early elective aortic valve surgery.

Assessment of left ventricular volumes and primary mitral regurgitation severity by 2D echocardiography and cardiovascular magnetic resonance.

BACKGROUND: Two-dimensional transthoracic echocardiography (2DTTE) remains the first-line diagnostic imaging tool to assess primary mitral regurgitation although cardiovascular magnetic resonance (CMR) has proven to establish left ventricular function more accurately and might evaluate mitral regurgitation severity more reliably. We sought to compare routine evaluation of left ventricular function and mitral regurgitation severity by 2DTTE with assessment by CMR in moderate to severe primary mitral regurgitation without overt left ventricular dysfunction. METHODS: We prospectively included 38 patients (79% of male, age 57 ± 14 years) with at least moderate primary mitral regurgitation, a left ventricular ejection fraction ≥60% and a left ventricular end-systolic diameter ≤45 mm. Patients with evidence of coronary artery disease, arrhythmias or significant concomitant valvular disease were excluded. All patients were scheduled for 2DTTE and CMR. RESULTS: Left ventricular end-diastolic and end-systolic volumes were significantly underestimated by 2DTTE in comparison with CMR, although there was a strong correlation (Pearson r = 0.81, p < 0.00001 and r = 0.7, p < 0.00001, respectively). Measurement of the regurgitant orifice was similar between 2DTTE PISA method and planimetry by CMR (47 ± 24 vs. 42 ± 16 mm2, p = 0.12) with a strong correlation between both imaging techniques (Pearson r = 0.76, p < 0.0001). By contrast, assessment of the regurgitant volume by 2DTTE and by phase contrast velocity mapping by CMR showed poor agreement. CONCLUSIONS: In moderate to severe primary mitral regurgitation without overt left ventricular dysfunction, 2DTTE significantly underestimates left ventricular remodelling in comparison to CMR. Measurement of the regurgitant orifice with planimetry by CMR shows good agreement with the PISA method by 2DTTE and thus may be a valuable alternative to assess mitral regurgitation severity.

Animal models of mitral regurgitation induced by mitral valve chordae tendineae rupture.

BACKGROUND AND AIM OF THE STUDY: Mitral regurgitation (MR) is a common valvular disease throughout the world. Various diagnostic techniques have been developed to assess the causes and severity of MR, and the therapeutic approaches to this disease have been widely documented. However, treatments for chronic MR remain controversial, and various animal models of chronic MR (including chordae tendineae rupture, rapid pacing and ischemia) have been developed to study the pathophysiology and therapeutic approaches to this condition. The study aim was to review the animal MR models that have been developed using a mitral valve chordae tendineae rupture technique. METHODS AND RESULTS: Among the animals used for these investigations, dogs and sheep have been most commonly used as models of MR induced by mitral valve chordae tendineae rupture, mainly due to considerations of cardiac size. Chordae tendineae cutting is performed using either closed- or open-chest techniques. In the closed-chest model, long flexible grasping forceps are positioned percutaneously in order to tear the mitral valve chordae. In the open-chest model, cardiopulmonary bypass is performed, and either selected chordae are cut under direct visualization or a non-specified number of chordae are cut, using a metal device inserted through the left ventricular apex. Whichever model is used, MR has been found to become chronic at three to six months after the induction of MR by chordae rupture. The reported mortality and complication rates of these models are high. CONCLUSION: In the long term, the experimental evolution of chronic MR is similar to the evolution occurring naturally in patients suffering from the condition. Hence, these models could be useful in understanding the disease better, and in testing new therapeutic modalities. The present review summarizes the physiological effects of each of these techniques, and compares the advantages and disadvantages of each procedure.

Exercise pulmonary hypertension in asymptomatic degenerative mitral regurgitation.

BACKGROUND: Current guidelines recommend mitral valve surgery for asymptomatic patients with severe degenerative mitral regurgitation and preserved left ventricular systolic function when exercise pulmonary hypertension (PHT) is present. However, the determinants of exercise PHT have not been evaluated. The aim of this study was to identify the echocardiographic predictors of exercise PHT and the impact on symptoms. METHODS AND RESULTS: Comprehensive resting and exercise transthoracic echocardiography was performed in 78 consecutive patients (age, 61+/-13 years; 56% men) with at least moderate degenerative mitral regurgitation (effective regurgitant orifice area =43+/-20 mm(2); regurgitant volume =71+/-27 mL). Exercise PHT was defined as a systolic pulmonary arterial pressure (SPAP) >60 mm Hg. Exercise PHT was present in 46% patients. In multivariable analysis, exercise effective regurgitant orifice was an independent determinant of exercise SPAP (P<0.0001) and exercise PHT (P=0.002). Resting PHT and exercise PHT were associated with markedly reduced 2-year symptom-free survival (36+/-14% versus 59+/-7%, P=0.04; 35+/-8% versus 75+/-7%, P<0.0001). After adjustment, although the impact of resting PHT was no longer significant, exercise PHT was identified as an independent predictor of the occurrence of symptoms (hazard ratio=3.4; P=0.002). Receiver-operating characteristics curves revealed that exercise PHT (SPAP >56 mm Hg) was more accurate than resting PHT (SPAP >36 mm Hg) in predicting the occurrence of symptoms during follow-up (P=0.032). CONCLUSIONS: Exercise PHT is frequent in patients with asymptomatic degenerative mitral regurgitation. Exercise mitral regurgitation severity is a strong independent predictor of both exercise SPAP and exercise PHT. Exercise PHT is associated with markedly low 2-year symptom-free survival, emphasizing the use of exercise echocardiography. An exercise SPAP >56 mm Hg accurately predicts the occurrence of symptoms.

Impact of aortic stiffness on left ventricular function and B-type natriuretic peptide release in severe aortic stenosis.

AIMS: In aortic stenosis (AS), both reduced systemic arterial compliance and increased valvular load have been shown to contribute to impaired left ventricular (LV) function. However, the relationship between LV function and aortic stiffness has not yet been investigated. We aimed to assess the relationship between aortic stiffness and LV global longitudinal strain (GLS), LV filling pressures (E/E') and B-type natriuretic peptide (BNP) in AS. METHODS AND RESULTS: A comprehensive echocardiogram was performed in 48 consecutive patients with severe AS (<0.6 cm(2)/m(2)) and preserved LV ejection fraction (≥50%). Aortic stiffness index (beta) was calculated based on aortic diameters measured by echocardiography and blood pressure. Systemic arterial compliance (SAC) and valvulo-arterial impedance (Z(va)) were also determined. Aortic beta index was significantly correlated with Z(va) (r = 0.30, P= 0.03) and SAC (r = -0.29, P = 0.04). GLS (r = 0.45, P = 0.001), E/E' (r = 0.48, P = 0.001) and BNP levels (r = 0.45, P = 0.001) were significantly related to aortic beta index. No significant correlation was found between GLS or E/E' and SAC or Z(va). In multivariate regression analysis, aortic beta index remained correlated with GLS, E/E', and BNP levels. CONCLUSIONS: In patients with severe AS and preserved LV ejection fraction, independently of the valvular load, an increase in aortic rigidity, as assessed by aortic beta index, is independently correlated with reduced LV longitudinal function, increased LV filling pressures, and BNP levels.