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In aortic stenosis (AS), left ventricular (LV) remodeling often occurs before symptom onset, and early intervention may be beneficial. Risk stratification remains challenging and identification of biomarkers may be useful. We evaluated the association between growth differentiation factor-15 (GDF-15) and soluble suppression of tumorigenicity 2 (sST2) and known markers of poor prognosis in AS. Baseline plasma GDF-15 and sST2 levels were measured in 70 patients with moderate-severe AS (aortic valve area1.5 cm

We aimed to compare cardiopulmonary exercise test (CPET) parameters, cardiac adaptations, and proportion of responders after different aerobic training programs amongst women and men with coronary heart disease (CHD). Patients with CHD were evaluated with a CPET and echocardiography before and after 3 months of aerobic exercise training. Peak oxygen uptake exercise training response was assessed according to the median peak oxygen uptake change for post- versus pretraining in the whole cohort (stratification non/low responders (NLR) vs. high-responders) and normalized for lean body mass (LBM). Eighty-three CHD patients were included (19 women, 64 men; 27 patients with interval, 19 with continuous, and 37 with combination exercises). Peak oxygen uptake, peak workload normalized for LBM, pulmonary variables (i.e., ventilation and oxygen uptake efficiency slope), and O2 pulse were significantly lower in women versus men. These parameters improved similarly with training in both sexes (p < 0.05). There were no differences in the proportion of NLR among women and men with CHD (7/19 (37%) vs. 35/64 (55%), p = 0.1719). Left ventricular ejection fraction and mean peak early diastolic mitral annulus velocity improved similarly with training in both sexes (p < 0.05). Women and men with CHD have a similar exercise training response regarding key CPET and echocardiographic parameters. The proportion of responders is similar. ClinicalTrials.gov: NCT03414996, NCT02048696, NCT03443193. Novelty: Cardiopulmonary adaptations to exercise training are similar among CHD men and women. Proportion of peak oxygen uptake for non/low/high responders is similar in CHD men and women. Left ventricular systolic and diastolic function improved similarly after exercise training in CHD men and women.

Objectives This study evaluated the impact of clinical and physiological factors limiting treatment optimization toward recommended medical therapy in heart failure (HF). Background Although guidelines aim to assist physicians in prescribing evidence-based therapies and to improve outcomes of patients with HF and reduced ejection fraction (HFrEF), gaps in clinical care persist. Methods Medical records of all patients with HFrEF followed for at least 6 months at the authors’ HF clinic (n = 511) allowed for drug optimization and were reviewed regarding the prescription rates of recommended pharmacological agents and devices (implantable cardioverter-defibrillator [ICD] or cardiac resynchronization therapy [CRT]). Then, an algorithm integrating clinical (New York Heart Association [NYHA] functional class, heart rate, blood pressure and biologic parameters (creatinine, serum potassium) based on the inclusion/exclusion criteria of landmark trials guiding these recommendations) was applied for each agent and device to identify potential explanations for treatment gaps. Results Gross prescription rates were high for beta-blockers (98.6%), mineralocorticoid receptor antagonist (MRA) (93.4%), vasodilators (90.3%), ICDs (75.1%), and CRT (82.1%) among those eligible, except for ivabradine (46.3%, n = 41). However, achievement of target physiological doses was lower (beta-blockers, 67.5%; MRA, 58.9%; and vasodilators, 63.4%), and one-fifth of patient dosages were still being up-titrated. Suboptimal doses were associated with older age (odds ratio [OR]: 1.221; p Conclusions Gaps in adherence to guidelines exist in specialized HF setting and are mostly explained by limiting physiological factors rather than inertia. Older age and history of stroke/TIA, potential markers of frailty, are associated with suboptimal doses of guideline-directed medical therapy, suggesting that an individualized rather than a “one-size-fits-all” approach may be required.

Linear aerobic training periodisation (LP) is recommended for patients with coronary heart disease (CHD). However, the effects of training periodisation on the right heart mechanics in patients with CHD have never been examined. This study aimed to explore the effects of LP and non-linear periodisation (NLP) on right heart mechanics. We prospectively randomised CHD patients to 12 weeks of aerobic training with LP or NLP. While there was a weekly increase in energy expenditure with LP, there was a steeper increase during the first 3 weeks, followed by a decrease in the fourth week with NLP. Echocardiography was performed at baseline and after the training period to assess the right ventricular free wall (RVFW) and right atrial strain. Thirty patients with CHD were included (NLP, n = 16; LP, n = 14). The traditional right and left heart parameters showed no significant time effects. There was a decrease of RVFW strain with time in both groups (+1.3 ± 0.9% with NLP, and +1.5 ± 0.8% with LP; p = 0.033). Mid-ventricular RVFW strain changed significantly with time (+2.0 ± 1.3% with NLP, and from +2.3 ± 1.2% with LP; p = 0.025). There was no time effect on the right atrial strain. In stable CHD patients, LP and NLP resulted in right ventricular strain decrements with a segment-specific pattern. This study was registered at ClinicalTrials.gov (identifier number: NCT03414996). Novelty: In stable coronary heart disease patients, both linear and non-linear aerobic training periodisation programs result in right ventricular strain decrements with time, particularly in the mid-ventricular segment. Traditional right and left heart parameters and right atrial strain showed no significant time effect in both 12 weeks aerobic training periodisation programs.

Background Aerobic exercise training is associated with beneficial ventricular remodeling and an improvement in cardiac biomarkers in chronic stable heart failure. High‐intensity interval training (HIIT) is a time‐efficient method to improve V˙O2peak in stable coronary heart disease patients. This pilot study aimed to compare the effect of HIIT on ventricular remodeling in patients with a recent acute myocardial infarction (AMI). Methods Nineteen post‐AMI patients were randomized to either HIIT (n = 9) or usual care (n = 10). A cardiopulmonary exercise test (CPET), transthoracic echocardiography, and cardiac biomarker assessment (ie, N‐terminal pro B‐type natriuretic peptide levels and G protein‐coupled receptor kinase 2 expression) were performed before and after a 12‐week training intervention. CPET parameters including oxygen uptake efficiency slope (OUES) and V˙O2 at the first ventilatory threshold (V˙O2 VT1) were calculated. left ventricular (LV) structural and functional echocardiographic parameters including myocardial strain imaging were assessed. Results V˙O2peak and OUES improved solely in the HIIT group (P

Objective: To compare the effects of high-intensity interval training versus moderate-intensity continuous training on risk markers of arrhythmic death in patients who recently suffered from an acute coronary syndrome. Design: Double-blind (patient and evaluator) randomized controlled trial. Setting: Cardiovascular Prevention and Rehabilitation Centre (EPIC Centre) of the Montreal Heart Institute, Montreal, Canada. Subjects: A total of 43 patients were randomized following an acute coronary syndrome. Interventions: Patients were assigned to either high-intensity interval training (n = 18) or isocaloric moderate-intensity continuous training (n = 19), three times a week for a total of 36 sessions. Main measures: Heart rate recovery for 5 minutes, heart rate variability for 24 hours, occurrence of ventricular arrhythmias, and QT dispersion were measured before and after the 36 sessions of training. Results: Among the 43 patients randomized, 6 participants in the high-intensity interval training group stopped training for reasons unrelated to exercise training and were excluded from the analyses. Heart rate recovery improved solely in the high-intensity interval training group, particularly at the end of recovery period ( p < 0.05). There were no differences in heart rate variability, occurrence of ventricular arrhythmias, or QT dispersion parameters between the groups at study end. Conclusion: Despite the lack of power to detect any large difference between the two interventions with respect to risk markers of arrhythmic death, high-intensity interval training appears safe and may be more effective at improving heart rate recovery relative to moderate-intensity continuous training in our patients following acute coronary syndrome.

We compared the impacts of linear (LP) and nonlinear (NLP) aerobic training periodizations on left ventricular (LV) function and geometry in coronary artery disease (CAD) patients. Thirty-nine CAD patients were randomized to either a 3-month isoenergetic supervised LP or NLP. All underwent standard echocardiography with assessment of 3D LV ejection fraction (LVEF), diastolic function, strain (global longitudinal, radial, and circumferential), and strain rate at baseline and study end. Training was performed 3 times/week and included high-intensity interval and moderate-intensity continuous training sessions. Training load was progressively increased in the LP group, while it was deeply increased and intercepted with a recovery week each fourth week in the NLP group. For the 34 analyzed patients, we found similar improvements for 3D LVEF (effect size (ES): LP, 0.29; NLP, 0.77), radial strain (ES: LP, 0.58; NLP, 0.48), and radial strain rate (ES: LP, 0.87; NLP, 0.17) in both groups (time for all: p ≤ 0.01). All other parameters of cardiac function remained similar. In conclusion, NLP and LP led to similar improvements in 3D LVEF and radial strain, suggesting a favourable positive cardiac remodelling through myofibers reorganization. These findings must be investigated in patients with more severe cardiac dysfunction. The study was registered on ClinicalTrials.gov (NCT03443193). Novelty: Linear and nonlinear periodization programs improved radial strain, accompanied by improvement of ejection fraction. Both aerobic periodization programs did not negatively impact cardiac function in coronary artery disease patients.

A lower heart rate (HR) during heat exposure is a classic marker of heat acclimation (HA), although it remains unclear whether this adaptation occurs secondary to reduced thermal strain and/or improvements in cardiac function. We evaluated the hypothesis that short-term passive HA reduces HR and improves cardiac function during passive heating. Echocardiography was performed under thermoneutral and hyperthermic conditions in 10 healthy adults (9 men/1 woman, 29 ± 6 yr old), pre and post 7 days of controlled hyperthermia. HR (P = 0.61), stroke volume (P = 0.99), and cardiac output (P = 0.99), were similar on days 1 and 7 of HA. Core (pre: 38.17 ± 0.42, post: 38.15 ± 0.27°C, P = 0.95) and mean skin (pre: 38.24 ± 0.41, post: 38.51 ± 0.29°C, P = 0.17) temperatures were similar during hyperthermic echocardiographic assessments. Cardiac systolic function was unaffected by HA (P ≥ 0.10). HA attenuated the decrease in end-diastolic volume (pre: -18 ± 18, post: -12 ± 19 mL, P = 0.05), accentuated the greater atrial contribution to diastolic filling (pre: +11 ± 5, post: +14 ± 5%, P = 0.02), and attenuated the increase in left atrial reservoir strain rate (pre: +1.5 ± 1.2, post: +0.8 ± 0.8 1/s, P = 0.02) during heating. Nonetheless, there were no differences in HR (pre: 106 ± 12, post: 104 ± 12 beats/min, P = 0.50), stroke volume (pre: 65 ± 15, post: 68 ± 13 mL, P = 0.55), or cardiac output (pre: 6.9 ± 2.0, post: 7.1 ± 1.7 L/min, P = 0.70) during passive heating. Short-term controlled hyperthermia HA results in limited adaptations of cardiac function during passive heating.NEW & NOTEWORTHY A lower heart rate during heat exposure is a classic marker of heat acclimation (HA). It remains unknown if improved cardiac function contributes to this response. A 7-day passive HA protocol did not alter cardiac systolic function during passive heating, whereas it improved some indexes of diastolic function in young adults. Nonetheless, heart rate during heating was unaffected by HA. These results suggest that passive HA induces limited adaptations in cardiac function during passive heating.

This study evaluated the impact of clinical and physiological factors limiting treatment optimization toward recommended medical therapy in heart failure (HF).Although guidelines aim to assist physicians in prescribing evidence-based therapies and to improve outcomes of patients with HF and reduced ejection fraction (HFrEF), gaps in clinical care persist.Medical records of all patients with HFrEF followed for at least 6 months at the authors' HF clinic (n = 511) allowed for drug optimization and were reviewed regarding the prescription rates of recommended pharmacological agents and devices (implantable cardioverter-defibrillator [ICD] or cardiac resynchronization therapy [CRT]). Then, an algorithm integrating clinical (New York Heart Association [NYHA] functional class, heart rate, blood pressure and biologic parameters (creatinine, serum potassium) based on the inclusion/exclusion criteria of landmark trials guiding these recommendations) was applied for each agent and device to identify potential explanations for treatment gaps.Gross prescription rates were high for beta-blockers (98.6%), mineralocorticoid receptor antagonist (MRA) (93.4%), vasodilators (90.3%), ICDs (75.1%), and CRT (82.1%) among those eligible, except for ivabradine (46.3%, n = 41). However, achievement of target physiological doses was lower (beta-blockers, 67.5%; MRA, 58.9%; and vasodilators, 63.4%), and one-fifth of patient dosages were still being up-titrated. Suboptimal doses were associated with older age (odds ratio [OR]: 1.221; p 0.0001) and history of stroke or transient ischemic attack (TIA) (no vs. yes, OR: 0.264; p = 0.0336).Gaps in adherence to guidelines exist in specialized HF setting and are mostly explained by limiting physiological factors rather than inertia. Older age and history of stroke/TIA, potential markers of frailty, are associated with suboptimal doses of guideline-directed medical therapy, suggesting that an individualized rather than a "one-size-fits-all" approach may be required.

Aortic stenosis (AS), 1 of the most common valve diseases in developed countries, carries a poor prognosis if left untreated. Transcatheter aortic valve replacement (TAVR) has become the standard of care for high-risk and inoperable patients with severe aortic stenosis (AS). Women represent a significant proportion of patients with severe AS and demonstrate specific clinical, anatomic, and pathophysiological features that are evident both before and after valve replacement. In this review, we discuss these features as well as the outcomes of women undergoing TAVR for AS.

Purpose Exercise tolerance has important prognostic value in patients with heart failure and reduced ejection fraction (HFrEF). The relationship between right ventricular function and its coupling to pulmonary circulation (RV-PA) and cardiopulmonary exercise tests (CPET) is not fully understood. We aimed to evaluate the value of RV echocardiographic parameters, including RV-PA, to predict exercise tolerance in HFrEF patients. Methods We performed a sub-analysis of EARTH, which enrolled HFrEF patients undergoing defibrillator implantation. At baseline, an echocardiogram and various CPET [peak VO2; minute ventilation/carbon dioxide production slope (VE/VCO2); 6-minute walk distance (6MWD) and submaximal exercise duration (SED)] were performed. The primary outcome was the correlation of RV-PA (using TAPSE/sPAP, tricuspid annular plane systolic excursion on pulmonary artery systolic pressure ratio (T/P)) with peak VO2. Secondary outcomes include correlation between various RV parameters such as size [diameter at inlet and end-diastolic area in apical 4-chamber], RV function [TAPSE; right ventricular fractional area change (RV-FAC); RV myocardial performance index (RV-MPI)], sPAP and tricuspid regurgitation grade (TRG); and CPET variables. Univariate and multivariate linear regression models were used on patients for which both TAPSE and sPAP were available. Results 205 patients were enrolled in EARTH, with 100 having data on both TAPSE and sPAP (Men: 70.0%; NYHA class II: 55.0%; mean LVEF 26.5±7.8%). T/P was the only parameter found to be predictive of peak VO2 (β=6.8, p Conclusion In HFrEF patients, RV-PA coupling (using TAPSE/sPAP) is a powerful predictor of maximal and submaximal exercise capacity and has a greater predictive value than the usual parameters including age, sex and LVEF.

With the improvement of cancer therapy, survival related to malignancy has improved, but the prevalence of long-term cardiotoxicity has also increased. Cancer therapies with known cardiac toxicity include anthracyclines, biologic agents (trastuzumab), and multikinase inhibitors (sunitinib). The most frequent presentation of cardiac toxicity is dilated cardiomyopathy associated with poorest prognosis. Monitoring of cardiac toxicity is commonly performed by assessment of left ventricular (LV) ejection fraction, which requires a significant amount of myocardial damage to allow detection of cardiac toxicity. Accordingly, this creates the impetus to search for more sensitive and reproducible biomarkers of cardiac toxicity after cancer therapy. Different biomarkers have been proposed to that end, the most studied ones included troponin release resulting from cardiomyocyte damage and natriuretic peptides reflecting elevation in LV filling pressure and wall stress. Increase in the levels of troponin and natriuretic peptides have been correlated with cumulative dose of anthracycline and the degree of LV dysfunction. Troponin is recognized as a highly efficient predictor of early and chronic cardiac toxicity, but there remains some debate regarding the clinical usefulness of the measurement of natriuretic peptides because of divergent results. Preliminary data are available for other biomarkers targeting inflammation, endothelial dysfunction, myocardial ischemia, and neuregulin-1. The purpose of this article is to review the available data to determine the role of biomarkers in decreasing the risk of cardiac toxicity after cancer therapy.

Nearly half of all patients with heart failure present with a preserved left ventricular ejection fraction (HFPEF). HFPEF is a pathophysiologically and clinically heterogeneous disease with an overall similar outcome to heart failure patients with a reduced ejection fraction. It is predominantly seen in elderly patients and comorbidities such as obesity, diabetes, hypertension, a sedentary lifestyle, and myocardial ischaemia play important roles in its development. In this chapter the conventional echocardiographic hallmarks of HFPEF including a preserved ejection fraction, left ventricular hypertrophy, left atrial dilatation, diastolic dysfunction, and pulmonary hypertension are presented. For the evaluation of left ventricular diastolic dysfunction, it is important to keep in mind that no single echocardiographic parameter is sufficiently accurate and reproducible to be used in isolation to make a diagnosis of diastolic dysfunction. The value of newer techniques including three-dimensional echocardiography and longitudinal strain assessment for the diagnosis and follow-up of HFPEF patients are promising but require further evaluation. As exercise-induced dyspnoea may be the first manifestation of HFPEF, the role of exercise echo (or diastolic stress testing) with evaluation of exercise-induced changes in left ventricular filling pressure and pulmonary artery systolic pressure is also presented. This chapter ends with a discussion on the echocardiographic parameters that can be used for risk stratification and follow-up of HFPEF patients.

Aortic stenosis (AS) is the most common valvular disease and aortic valve replacement (AVR) is indicated in symptomatic patients or with decline in left ventricular ejection fraction (LVEF). LV remodelling and diastolic dysfunction often occur prior to symptom onset and earlier AVR may be beneficial

Pro-inflammatory angiopoietin-like 2 (angptl2) promotes endothelial dysfunction in mice and circulating angptl2 is higher in patients with cardiovascular diseases. We previously reported that a single bout of physical exercise was able to reduce angptl2 levels in coronary patients. We hypothesized that chronic exercise would reduce angptl2 in patients with post-acute coronary syndrome (ACS) and endothelial dysfunction. Post-ACS patients (n = 40, 10 women) were enrolled in a 3-month exercise-based prevention program. Plasma angptl2, hs-CRP, and endothelial function assessed by scintigraphic forearm blood flow, were measured before and at the end of the study. Exercise increased VO2peak by 10% (p

Background. - Early detection of pulmonary arterial hypertension (PH) is crucial in systemic scleroderma. However, predictors of new onset of resting PH during follow-up (FUPH) have been poorly explored. Aim. - To determine whether nailfold videocapillaroscopy (NVC) grade and exercise echocardiographic variables are predictors of FUPH. Methods. - We prospectively enrolled 40 patients with systemic sclerosis (age 54 13 years; 68% women). All patients underwent graded semisupine exercise echocardiography and NVC. Baseline resting PH and FUPH were defined as systolic pulmonary arterial pressure (sPAP) > 35 mmHg, and exercise-induced PH (EIPH) as exercise sPAP > 50 mmHg. Results. - Seventeen patients developed EIPH (43%). During follow-up (FU) (25 15 months), 11 patients without baseline PH developed FUPH (28%), all from the EIPH group. Patients with FUPH were significantly older (60 +/- 14 vs 50 +/- 12 years; P = 0.04), had higher resting and exercise sPAP (30 +/- 4 vs 22 +/- 5 and 60 +/- 12 vs 40 +/- 11 mmHg, respectively; P < 0.0001) and a higher exercise E/e' ratio (9.4 +/- 0.7 vs 5.8 +/- 0.4; P = 0.0003) and presented more frequently NVC grade > 2 (90% vs 35%; P = 0.0009). After adjustment for age, resting sPAP, exercise sPAP and NVC grade > 2 were associated with maximal resting sPAP during follow-up and FUPH (P < 0.05). Patients with both EIPH and NVC grade > 2 had a very high incidence of FUPH (82%), and both variables remained strongly associated with FUPH after adjustment for age (hazard ratio 11.6, 95% confidence interval 2.4-55.3; P = 0.002). Conclusion. - Exercise echocardiography and NVC can identify a subgroup of patients with systemic sclerosis who are at risk of developing FUPH.

Background— Atrial fibrillation (AF) is common after thoracic surgery. Limited data exist concerning the incidence of AF, its impact on mortality, the effectiveness of therapy, and the risk factors of AF after pulmonary transplantation. Methods and Results— We reviewed the medical files of 224 consecutive lung transplant recipients who underwent surgery over a 10-year period at a large Canadian center. We collected patient characteristics, in-hospital treatments, and outcomes. Time-to-event analysis was used to account for in-hospital follow-up and models generated to assess the impact of AF on mortality and independent risk factors of AF after transplantation. Postoperative AF occurred in 65 patients (29%). AF was more likely to occur with complications such as pneumonia, mediastinitis, and bronchial dehiscence and was not an independent risk factor of mortality (hazard ratio=1.56; 95% confidence interval, 0.52–4.63). Pharmacological or electric therapy for rhythm or rate control of AF was administered to 97% of patients. Intravenous amiodarone was used in 46%, electric cardioversion in 28%, and heparin in 26%. Only 1 patient remained in AF at discharge. Age (hazard ratio=1.08 by year; 95% confidence interval, 1.05–1.12), bilateral transplantation (hazard ratio=1.87; 95% confidence interval, 1.03–3.42), and a history of AF before the transplantation (hazard ratio=4.48; 95% confidence interval, 1.05–19.11) were found to be independently associated with an increased incidence of postoperative AF. Conclusions— AF is fairly common after pulmonary transplantation, transient, and relatively benign. It is not independently associated with increased in-hospital mortality. Most patients return to sinus rhythm before discharge. Age, prior AF, and bilateral transplantation increase the risk of postoperative AF.

Acute decompensated heart failure (ADHF) is the most common cause of hospitalization in North America, and it is associated with high mortality and the need for frequent early rehospitalization. Despite the magnitude of the problem, there have been few advances in its therapy, perhaps because ADHF is the result of the convergence of multiple different factors, including progressive fluid retention, neurohumoral activation, further reduction in cardiac output, vasoconstriction, and hypertension, tachycardia, and impaired coronary perfusion in the face of increased demand (Fig. 1). Therapy is frequently complicated by the presence of comorbidities such as renal dysfunction, mitral regurgitation, supraventricular arrhythmias, and diabetes. The search for a trigger leading to ADHF has generally identified progressive fluid retention and the resultant overactivation of normally compensatory neurohumoral systems as playing a central role in the process, but it may be that progressive volume overload is simply a sign of the convergence of abnormalities that result from the multiple comorbidities that exist in such patients. In search of the precipitating cause of acute pulmonary edema (APE), the article, “Acute Hypertension in Acute Pulmonary Edema: Mostly a Trigger or an Associated Phenomenon?” by Figueras et al., presents a careful documentation of multiple characteristics of 742 patients admitted to their coronary care unit with a particularly severe form of ADHF, ie, APE. In this prospective registry, patients systematically had echocardiographic as well as phenotypic and biomarker assessments, and 468 (63%) patients had coronary angiography. The authors found that 78% of patients had coronary artery disease (CAD) defined as previous myocardial infarction or acute coronary syndrome (ACS) or coronary stenosis 70%; 65% had ACS defined as acute myocardial infarction with increased levels of creatine kinase-MB (CKMB) mass > 10 mg/L with or without chest pain or

International audience; B-type natriuretic peptide (BNP) is often used as a complementary finding in the diagnostic work-up of patients with aortic stenosis (AS). Whether soluble ST2, a new biomarker of cardiac stretch, is associated with symptomatic status and outcome in asymptomatic AS is unknown. sST2 and BNP levels were measured in 86 patients (74±13 years; 59 asymptomatic, 69%) with AS (23 ng/mL, AUC = 0.68, p

Background: The aim of this study was to determine the impact on the outcome of serial B-type natriuretic peptide (BNP) changes during follow-up in asymptomatic patients with >= moderate aortic stenosis (AS) and preserved left ventricular ejection fraction. Methods: We prospectively screened 69 patients who underwent comprehensive transthoracic echocardiography, BNP level measurement at baseline and after every 6 or 12 months. Annualized BNP changes were calculated as the difference between the last and baseline BNP measurements divided by the duration of follow-up. The primary endpoint was the occurrence of symptoms, aortic valve replacement, or cardiovascular death. Results: During a follow-up of 30 +/- 19 months, 43 patients experienced a cardiac event. These patients were significantly older (73 +/- 9 vs 65 +/- 16 years; P = 0.010), had more often dyslipidemia (79% vs 42%; P = 0.038), more severe AS (peak velocity: 3.9 +/- 0.6 vs 3.5 +/- 0.6 m/s; P = 0.002), larger indexed left atrial area (10.2 +/- 2.5 vs 8.7 +/- 1.9 cm(2)/m(2); P = 0.006), and a higher increase in annualized BNP (+90 +/- 155 vs +7 +/- 49 pg/mL/y; P = 0.010). Patients with higher annualized BNP changes (> 20 pg/mL/y) had a significantly lower cardiac event-free survival (1 year: 63 +/- 8% vs 97 +/- 3%; 3 years: 31 +/- 8% vs 68 +/- 8%; P < 0.001). Using the multivariate Cox proportional hazards model, higher annualized BNP changes were significantly associated with increased risk of cardiac events (hazard ratio: 2.73, 95% confidence interval: 1.27-5.86; P = 0.010) after adjustment for age, dyslipidemia, and echocardiographic parameters. Conclusions: In asymptomatic patients with AS and preserved left ventricular ejection fraction, the use of serial BNP changes may help to anticipate development of class I indication for aortic valve replacement.

High altitude (HA) pulmonary edema (PE) results from complex and misunderstood interactions between adaptation mechanisms. We assessed the occurrence of subclinical PE and brain natriuretic peptide (BNP) levels among nonacclimatized individuals during an expedition on Mount Elbrus (5642 m).Seven subjects underwent assessment of vital signs, Lake Louise Score, ultrasound lung comets using handheld echography and circulating BNP using capillary testing at different stages of ascension, in addition to baseline echocardiography. Friedman tests were used to compare serial measurements.Heart rate, Lake Louise Score (P0.0001) and blood pressure (P = 0.037) increased during ascension; oxygen saturation decreased (P0.0001). BNP increased (40.7 ± 16.8 vs 19.7 ± 3.04 pg/mL; P0.01) after the summit, as did ultrasound lung comet count throughout ascension (P0.0001), but both parameters were not correlated (r = 0.36; P = 0.42). Post-summit peak BNP correlated with baseline left ventricular mass index (r = -0.79; P = 0.033).This study confirms the high incidence of subclinical PE during subacute exposure to hypobaric hypoxia and enhancement of this phenomenon after exertion. Although not correlated with the degree of PE, BNP levels increased after sustained effort at HA, but not at rest. Further investigation is needed to determine the mechanisms underlying the BNP response at HA and its usefulness as a monitoring tool during expeditions.

Secondary mitral valve regurgitation (SMR) is a complex disease involving distortion of the mitral valve component and left ventricular geometry, mainly caused by chronic coronary artery disease. The indication of coronary artery bypass grafting and the severity of regurgitation should guide the decision to intervene. Surgical repair is indicated in patients with left ventricular ejection fraction >30 % undergoing revascularization and severe mitral regurgitation, as it should be considered in moderate regurgitation, especially if a high likelihood of reparability or a significant dynamic component is documented. In patients without a clear indication of revascularization, the assessment of myocardial viability and coronary status is mandatory. Symptomatic patients with severe mitral regurgitation, left ventricular ejection fraction less than 30 % and option for revascularization with evidence of viability should benefit from repair. In contrast, symptomatic patients with severe mitral regurgitation and left ventricular ejection fraction >30 %, but without possibility of revascularization, should be operated only if they remain symptomatic despite optimal medical treatment and present low comorbidity. For others, medical treatment or even cardiac transplantation is preferred. However, thesurvival benefit of mitral valve repair compared to revascularization alone has not been demonstrated in randomized studies and thus controversy according to optimal therapy persists. Revascularization alone is generally not sufficient to adequately address moderate-severe mitral regurgitation and chronic functional regurgitation following previous surgery is associated with worse prognosis, justifying the addition of a mitral valve procedure. However, the choice of ideal procedure remains litigious. Even if complications related to mitral valve replacement are avoided with repair, this may be counterbalanced by the high rate of persistent/recurrent mitral regurgitation, which may be anticipated using comprehensive preoperative echocardiography.

B-type natriuretic peptide (BNP) level may be a useful prognostic marker for the management of asymptomatic patients with aortic stenosis (AS). The aim of this study was to identify the echocardiographic determinants of BNP changes during follow-up in AS. We studied 61 asymptomatic patients with greater than moderate AS and preserved left ventricular (LV) ejection fraction who underwent rest and exercise Doppler echocardiography with concomitant BNP level measurement at baseline. BNP measurement was repeated after inclusion every 6 months. Patients were divided into 2 groups according to the median of BNP changes during follow-up. According to parameters at rest, patients in the high BNP changes group had significantly higher E/e′ ratio. Statistically significant correlations were found between BNP changes and E/e′ ratio and indexed left atrial area. According to exercise parameters, patients in the high BNP changes group had significantly lower exercise-induced increase in LV ejection fraction. Statistically significant correlations were found between BNP changes and exercise-induced changes in LV ejection fraction. After adjustment for age, mean aortic pressure gradient, and BNP level at baseline, multivariate analysis identified indexed left atrial area, E/e′ at rest, and exercise-induced increase in ejection fraction as independent determinants of BNP changes during follow-up. In conclusion, this study shows that, in asymptomatic patients with preserved LV function and moderate AS, serial BNP measurements may widely vary. Subclinical LV diastolic and systolic dysfunctions are frequently present in patients with higher serial BNP changes.

Resting and exercise echocardiographic determinants Christine Henri , Julien Magne , Raluca Dulgheru , Saloua Laaraibi , Damien Voilliot , Seisyou Kou , Luc Pierard ⁎, Patrizio Lancellotti a,⁎ a University of Liege Hospital, GIGA Cardiovascular Sciences, Department of Cardiology, Heart Valve Clinic, CHU Sart Tilman, Liege, Belgium b University of Montreal, Department of Medicine, Montreal Heart Institute, Canada

AimsAvailability of normative reference values for cardiac chamber quantitation is a prerequisite for accurate clinical application of echocardiography. In this study, we report normal reference ranges for cardiac chambers size obtained in a large group of healthy volunteers accounting for gender and age. Echocardiographic data were acquired using state-of-the-art cardiac ultrasound equipment following chamber quantitation protocols approved by the European Association of Cardiovascular Imaging.MethodsA total of 734 (mean age: 45.8 ± 13.3 years) healthy volunteers (320 men and 414 women) were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was performed on all subjects following pre-defined protocols. There were no gender differences in age or cholesterol levels. Compared with men, women had significantly smaller body surface areas, and lower blood pressure. Quality of echocardiographic data sets was good to excellent in the majority of patients. Upper and lower reference limits were higher in men than in women. The reference values varied with age. These age-related changes persisted for most parameters after normalization for the body surface area.ConclusionThe NORRE study provides useful two-dimensional echocardiographic reference ranges for cardiac chamber quantification. These data highlight the need for body size normalization that should be performed together with age-and gender-specific assessment for the most echocardiographic parameters. © 2014 The Author.

The role of exercise testing and stress imaging in the management of patients with valvular heart disease (VHD) is reviewed in this article. The American College of Cardiology/American Heart Association and the European Society of Cardiology/European Association of Cardiothoracic Surgery have recently put emphasis on the role of exercise testing to clarify symptom status and the use of stress imaging to assess the dynamic component of valvular abnormalities and unmask subclinical myocardial dysfunction that could be missed at rest. Recent studies have demonstrated the incremental prognostic value of exercise echocardiography for asymptomatic patients with severe aortic stenosis, moderate-severe mitral stenosis, and severe primary mitral regurgitation. In patients with low-flow, low-gradient aortic stenosis, dobutamine stress echocardiography is recommended to differentiate true severe from pseudosevere aortic stenosis. Data on the prognostic value of stress echocardiography in aortic regurgitation and functional mitral regurgitation are less robust. Data are sparse on the use of stress imaging in right-sided VHD, however recent studies using stress cardiovascular magnetic resonance imaging offer some prognostic information. Although the strongest recommendations for surgical treatment continue to be based on symptom status and resting left ventricular repercussions, stress imaging can be useful to optimize risk stratification and timing of surgery in VHD. Randomized clinical trials are required to confirm that clinical decision-making based on stress imaging can lead to improved outcomes.

Exercise-induced pulmonary arterial hypertension (EIPH) in systemic sclerosis (SSc) has already been observed but its determinants remain unclear. The aim of this study was to determine the incidence and the determinants of EIPH in SSc.We prospectively enrolled 63 patients with SSc (age 54±3years, 76% female) followed in CHU Sart-Tilman in Liège. All patients underwent graded semi-supine exercise echocardiography. Systolic pulmonary arterial pressure (sPAP) was derived from the peak velocity of the tricuspid regurgitation jet and adding the estimation of right atrial pressure, both at rest and during exercise. Resting pulmonary arterial hypertension (PH) was defined as sPAP35 mmHg and EIPH as sPAP50 mmHg during exercise. The following formulas were used: mean PAP (mPAP) = 0.61 × sPAP + 2, left atrial pressure (LAP)=1.9+1.24 × left ventricular (LV) E/e' and pulmonary vascular resistance (PVR)=(mPAP-LAP)/LV cardiac output (CO) and slope of mPAP-LVCO relationship=changes in mPAP/changes in LVCO. Resting PH was present in 3 patients (7%) and 21 patients developed EIPH (47%). Patients with EIPH had higher resting LAP (10.3 ± 2.2 versus 8.8 ± 2.3 mmHg; p = 0.03), resting PVR (2.6 ± 0.8 vs. 1.4 ± 1.1 Woods units; p=0.004), exercise LAP (13.3 ± 2.3 vs. 9 ± 1.7 mmHg; p0.0001), exercise PVR (3.6 ± 0.7 vs. 2.1 ± 0.9 Woods units; p = 0.02) and slope of mPAP-LVCO (5.8 ± 2.4 vs. 2.9 ± 2.1 mmHg/L/min; p0.0001). After adjustment for age and gender, exercise LAP (β=3.1 ± 0.8; p=0.001) and exercise PVR (β=7.9 ± 1.7; p=0.0001) were independent determinants of exercise sPAP.EIPH is frequent in SSc patients and is mainly related to both increased exercise LV filling pressure and exercise PVR.

With the improvement of cancer therapy, survival related to malignancy has improved, but the prevalence of long-term cardiotoxicity has also increased. Cancer therapies with known cardiac toxicity include anthracyclines, biologic agents (trastuzumab), and multikinase inhibitors (sunitinib). The most frequent presentation of cardiac toxicity is dilated cardiomyopathy associated with poorest prognosis. Monitoring of cardiac toxicity is commonly performed by assessment of left ventricular (LV) ejection fraction, which requires a significant amount of myocardial damage to allow detection of cardiac toxicity. Accordingly, this creates the impetus to search for more sensitive and reproducible biomarkers of cardiac toxicity after cancer therapy. Different biomarkers have been proposed to that end, the most studied ones included troponin release resulting from cardiomyocyte damage and natriuretic peptides reflecting elevation in LV filling pressure and wall stress. Increase in the levels of troponin and natriuretic peptides have been correlated with cumulative dose of anthracycline and the degree of LV dysfunction. Troponin is recognized as a highly efficient predictor of early and chronic cardiac toxicity, but there remains some debate regarding the clinical usefulness of the measurement of natriuretic peptides because of divergent results. Preliminary data are available for other biomarkers targeting inflammation, endothelial dysfunction, myocardial ischemia, and neuregulin-1. The purpose of this article is to review the available data to determine the role of biomarkers in decreasing the risk of cardiac toxicity after cancer therapy.

In patients with heart failure (HF), left atrial (LA) function plays a central role in maintaining optimal cardiac output despite impaired left ventricular (LV) relaxation and reduced LV compliance. 1 It has been demonstrated that the Frank-Starling mechanism is also operative in the left atrium and that LA output increases as atrial diameter increases, which contributes to maintain a normal stroke volume. In a non-compliant left ventricle, as the left atrium is exposed to the pressures of the left ventricle during diastole, LA pressure rises to maintain adequate LV filling. The resulting increase in LA wall tension, through myocyte stretch, induces myolysis, fibrosis, and apoptosis, and leads to progressive LA enlargement, which tends to prevent passive transmission of pressure to the pulmonary circulation. 2,3 Clinically, LA enlargement is most commonly expressed by the maximum LA volume obtained at end-systole when LA chamber is at its greatest dimension. It should be noted that left atrium is not a symmetrically shaped three-dimensional (3D) structure, and that LA enlargement is not a uniform process. Therefore, measurement of the left atrium by M-mode echocardiography is likely to be an insensitive assessment of any change in size of the left atrium. Conversely, LA volume by two-dimensional (2D)/3D echocardiography provides a more accurate and reproducible estimate of the size of the left atrium. 4 Because a large number of individuals with LV dysfunction are in a pre-clinical phase of the disease, 5 increased LV filling pressures (E/e ' ) could only be expressed during exercise. The causes of increased E/ewith exercise are not well characterized. In a group of patients with a resting a E/e ' 1 3i n12% of the population) were those with larger LA volumes at rest. A LA volume index >33 mL/m 2 ,a cut-off already shown associated with increased risk of developing symptomatic HF, 7 predicted abnormal exercise LV filling pressures with a high sensitivity (91%) and a good specificity (78%), while a LA volume index

70 Paravalvular aortic regurgitation after autoexpandibles aortic protheses. Comparison between Edwards-Sapien protheses and Perceval sutureless aortic valve. {#article-title-2} Purpose: The transcatheter aortic valve implantation (TAVI) has proved to be an alternative treatment for severe aortic stenosis in high risk patients. New surgical techniques with autoexpandibles suturless aortic valve protheses have shown good results with a less invasive surgical approach and a reduction in surgical time. The purpose of the study was to compare initial echocardiographic results after aortic valve implantation by both techniques. Methods: We studied 142 consecutive patients submitted to TAVI and 33 patients submitted to aortic valve replacement (AVR) with autoexpandibles sutureless Perceval valves. Clinical and demographic variables were registered and a transthoracic echocardiography study was performed before the implantation and after the procedure or surgery. Maximum and mean aortic gradients were registered as well as the paravalvular aortic regurgitation (AR). The latter was classified in two grades: I= null o mild; II= moderate or severe. Results: The 142 patients submitted to TAVI were diagnosed of symptomatic severe aortic stenosis with a high surgical risk (Logistic EuroSCORE 10,4 ± 7,8), and higher age than the ones submitted to surgery (81,8 vs. 79,8; p=0,005). From the 33 patients submitted to AVR with Perceval protheses, 5 of them (15%) were also performed a coronary artery bypass graft. The incidence of paravalvular AR was grade I (null o mild) in 25 patients (86%), and grade II (moderate or severe) in 4 (14%). In patients with TAVI, 94 of them (69,1%) presented null or minimum paravalvular AR, while in the 42 remaining patients (30,9%) it was grade II, with statistically significant differences between the 2 types of protheses ( p=0,046). Both protheses presented similar aortic gradients in the study after the implantation, without statistically significant differences between TAVI and Perceval protheses in maximum Doppler gradient (20,98 vs. 23,87 mmHg; p= 0.152) and mean gradient (11,16 vs. 13,31 mmHg; p=0.063). The relation between time-velocity integral of the LV outflow tract and aortic valve after the implantation was also similar between both groups (median 0,55 vs. 0,53; p= 0,228). Conclusions: The early echocardiographic study after the implantation of autoexpandible aortic protheses shows comparable results between both types of protheses in terms of gradients, with a higher incidence of paravalvular aortic regurgitation in the group of TAVI. # 71 Exercise echocardiographic determinants of BNP changes during follow-up in asymptomatic patients with aortic stenosis and preserved left ventricular function {#article-title-3} Purpose: B-type natriuretic peptide (BNP) level may be a useful prognostic marker in asymptomatic patients with severe aortic stenosis (AS). Recently updated European Society of Cardiology guidelines recommend its measurement and the use of exercise stress echocardiography to optimize risk stratification in these patients. The goal of this study was to correlate exercise echocardiographic data and BNP changes during follow-up in asymptomatic patients with AS and preserved left ventricular (LV) function. Methods: We studied 61 asymptomatic patients (age: 70±13 years; 64% of males) with ≥ moderate AS (aortic valve area: 0.98±0.25cm2) and preserved LV ejection fraction (69±6%) who underwent resting and exercise Doppler echocardiography with concomitant BNP level measurement at baseline. None of the patients developed symptoms during test. BNP measurement was repeated after at least 6-months follow-up (22±12.5 months; median: 20; range: 7-47 months) and then each 6- or 12-month, according to the individual management. Results: From baseline to the last BNP measurement during follow-up, the distribution of BNP changes was: 65.5±129.5pg/mL; median: 29; range: -104-+675pg/mL. Patients were divided into 2 groups according to the median of serial BNP changes. There were no significant differences regarding clinical characteristics (all p

Background: Resting pulmonary hypertension (PH) is a powerful determinant of poor outcome in patients with systemic scleroderma (SSc). In various cardiac diseases, exercise-induced PH (EIPH) is considered as an early stage of resting PH, and may predict the occurrence of adverse events. We hypothesized that the presence of EIPH is a predictor of the onset of resting PH in patients with SSC. Methods: 33 patients with diagnosis of SSc disease were prospectively submitted to comprehensive both resting and exercise stress echocardiography between January 2009 and November 2012. Resting PH was defined as a transtricuspid pressure gradient (TTG) ≥ 30mmHg, and EIPH as TTG ≥ 40 mmHg Patients were prospectively follow-up and regularly performed resting echocardiography. Results: There was a significant increase in TTG from rest to exercise (21.5±7.7 vs. 37.5±15.2, p