Cardiac function during heat stress: impact of short-term passive heat acclimation.

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.

Effects of interval training on risk markers for arrhythmic death: a randomized controlled trial.

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.

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.

Growth Differentiation Factor-15 as a Predictor of Functional Capacity, Frailty, and Ventricular Dysfunction in Patients With Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

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 area <1.5 cm2) and preserved LV ejection fraction (>45%). Patients were categorized into "low GDF-15" versus "high GDF-15" and "low sST2" versus "high sST2" groups. Groups were compared for differences in cardiovascular risk factors, 6-minute walk test, 5 m gait speed, cognitive function (Montreal Cognitive Assessment), and echocardiographic parameters. Overall, 44% of patients were deemed asymptomatic by New York Heart Association class, 61% had severe AS (aortic valve area <1 cm2) and all patients had preserved LV ejection fraction. GDF-15 levels were not predictive of AS severity. However, high GDF-15 (>1,050 pg/ml) was associated with LV dysfunction as shown by lower indexed stroke volume (p <0.01), worse LV global longitudinal strain (p = 0.04), greater mean E/e' (p = 0.02) and indexed left atrial volume (p <0.01). It was also associated with decreased functional capacity with shorter 6-minute walk test (p = 0.01) and slower 5 m gait speed (p = 0.02). Associations between sST2 levels and markers of poor prognosis were less compelling. In this study of patients with moderate to severe AS, elevated GDF-15 levels are associated with impaired functional capacity, poorer performance on fragility testing, and LV dysfunction. In conclusion, GDF-15 may integrate these markers of adverse outcomes into a single biomarker of poor prognosis.

Right ventricular function and its coupling to pulmonary circulation predicts exercise tolerance in systolic heart failure.

AIMS: Right ventricular (RV) dysfunction, pulmonary hypertension, and exercise intolerance have prognostic values, but their interrelation is not fully understood. We investigated how RV function alone and its coupling with pulmonary circulation (RV-PA) predict cardio-respiratory fitness in patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS: The Evaluation of Resynchronization Therapy for Heart Failure (EARTH) study included 205 HFrEF patients with narrow (n = 85) and prolonged (n = 120) QRS duration undergoing implantable cardioverter defibrillator implantation. All patients underwent a comprehensive evaluation with exercise tolerance tests and echocardiography. We investigated the correlations at baseline between RV parameters {size, function [tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV-FAC), and RV myocardial performance index (RV-MPI)], pulmonary artery systolic pressure (PASP), and tricuspid regurgitation}; left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVi), and left atrial volume index (LAVi); and cardiopulmonary exercise test (CPET) [peak VO2 , minute ventilation/carbon dioxide production (VE/VCO2 ), 6 min walk distance (6MWD), and submaximal exercise duration (SED)]. We also studied the relationship between RV-PA coupling (TAPSE/PASP ratio) and echocardiographic parameters in patients with both data available. Univariate and multivariate linear regression models were used. Patients enrolled in EARTH (overall population) were mostly male (73.2%), mean age 61.0 ± 9.8 years, New York Heart Association class II-III (87.8%), mean LVEF of 26.6 ± 7.7%, and reduced peak VO2 (15.1 ± 4.6 mL/kg/min). Of these, 100 had both TAPSE and PASP available (TAPSE/PASP population): they exhibited higher BNP, wider QRS duration, larger LVEDVi, with more having tricuspid regurgitation compared with the 105 patients for whom these values were not available (all P < 0.05). RV-FAC (ß = 7.5), LAVi (ß = -0.1), and sex (female, ß = -1.9) predicted peak VO2 in the overall population (all P = 0.01). When available, TAPSE/PASP ratio was the only echocardiographic parameter associated with peak VO2 (ß = 6.8; P < 0.01), a threshold ≤0.45 predicting a peak VO2  ≤ 14 mL/kg/min (0.39 for VO2  ≤ 12). RV-MPI was the only echocardiographic parameter associated with ventilatory inefficiency (VE/VCO2 ) and 6MWD (ß = 21.9 and ß = -69.3, respectively, both P ≤ 0.01) in the overall population. In presence of TAPSE/PASP, it became an important predictor for those two CPET (ß = -18.0 and ß = 72.4, respectively, both P < 0.01), together with RV-MPI (ß = 18.5, P < 0.01) for VE/VCO2 . Tricuspid regurgitation predicted SED (ß = -3.2, P = 0.03). CONCLUSIONS: Right ventricular function assessed by echocardiography (RV-MPI and RV-FAC) is closely associated with exercise tolerance in patients with HFrEF. When the TAPSE/PASP ratio is available, this marker of RV-PA coupling becomes the stronger echocardiographic predictor of exercise capacity in this population, highlighting its potential role as a screening tool to identify patients with reduced exercise capacity and potentially triage them to formal peak VO2 and/or evaluation for advanced HF therapies.

Impact of aerobic training periodisation on global and regional right ventricular strain in coronary heart disease.

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.

Impact of 2 different aerobic periodization training protocols on left ventricular function in patients with stable coronary artery disease: an exploratory study.

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.

Women and men with coronary heart disease respond similarly to different aerobic exercise training modalities: a pooled analysis of prospective randomized trials.

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.

Assessing Splanchnic Compartment Using Portal Venous Doppler and Impact of Adding It to the EVEREST Score for Risk Assessment in Heart Failure.

BACKGROUND: The Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) score has proven useful for risk prediction in acute decompensated heart failure (ADHF). However, this score does not include the characterization of the splanchnic compartment, which has been involved in worsening heart failure. Refining this score by integrating an assessment of the splanchnic compartment would allow for a better risk assessment. Therefore, we aimed to characterize the patterns of portal vein pulsatility (PVP), an ultrasound metric used for the assessment of splanchnic compartment and their determinants in patients with ADHF, to explore the relationships between abnormal patterns of PVP and outcomes, and to evaluate the added value of PVP to the EVEREST score for risk assessment in ADHF. METHODS: Portal vein flow was assessed prospectively on admission and at discharge in 95 patients with ADHF using pulsed-wave Doppler. Abnormal PVP was defined for values ≥ 50%. Cox proportional hazards models were used for the assessment of the relationship between PVP and outcomes. RESULTS: Overall, 64% of patients on admission and 24% at discharge had abnormal PVP. PVP on admission was inversely correlated with right ventricular function (tricuspid annular plane systolic excursion, ρ = -0.434) and pulmonary pressure (ρ = 0.346), P < 0.05. Although PVP was associated with all-cause mortality (hazard ratio, 1.028, P < 0.001), the addition of this metric to the EVEREST score had little effect on its C-index (0.813 vs 0.818) for risk assessment. CONCLUSIONS: Abnormal PVP is frequent and associated with right ventricular dysfunction in ADHF. Although abnormal PVP identifies higher-risk patients, this metric does not improve the performance of the EVEREST score for risk assessment.

CONTEXTE: Le score EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) s'avère utile pour la prévision du risque dans les cas d'insuffisance cardiaque décompensée aiguë (ICDA). Cependant, ce score ne permet pas de caractériser le compartiment splanchnique, impliqué dans l'aggravation de l'insuffisance cardiaque. Affiner ce score en y intégrant une évaluation du compartiment splanchnique permettrait une meilleure évaluation du risque. Par conséquent, nous avons entrepris de caractériser les profils de la pulsatilité du flux de la veine porte (PFVP) (mesure échographique permettant d'évaluer le compartiment splanchnique et ses déterminants dans les cas d'ICDA) afin d'examiner les relations entre les profils anormaux de la PFVP et les résultats, et afin d'évaluer la valeur ajoutée de la PFVP dans l'évaluation du risque faisant appel au score EVEREST chez des patients atteints d'ICDA. MÉTHODOLOGIE: Le flux de la veine porte a été évalué prospectivement par échographie Doppler pulsée à l'admission et à la sortie de 95 patients atteints d'ICDA. La définition d'une PFVP anormale ciblait des valeurs de 50 % ou plus. Des modèles à risques proportionnels de Cox ont servi à évaluer la relation entre la PFVP et les résultats. RÉSULTATS: Globalement, la PFVP était anormale à l'admission chez 64 % des patients et à la sortie chez 24 % des patients. Une corrélation inverse a été notée entre la PFVP à l'admission et la fonction ventriculaire droite (excursion annulaire horizontale systolique de la tricuspide, ρ = -0,434) ainsi que la pression pulmonaire (ρ = -0,346), p < 0,05. Bien que la PFVP ait été associée à la mortalité toutes causes confondues (rapport des risques instantanés de 1,028, p < 0,001), l'ajout de cette mesure au score EVEREST a eu peu d'effet sur son indice C (0,813 vs 0,818) pour l'évaluation du risque. CONCLUSIONS: Une PFVP anormale est d'observation courante et se trouve associée à une dysfonctionn ventriculaire droite dans les cas d'ICDA. Bien qu'une PFVP anormale permette de déceler les patients qui présentent un risque plus élevé, son objectivation n'améliore pas la précision du score EVEREST dans l'évaluation du risque.

Care Gaps in Adherence to Heart Failure Guidelines: Clinical Inertia or Physiological Limitations?

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 < 0.0001) and history of stroke or transient ischemic attack (TIA) (no vs. yes, OR: 0.264; p = 0.0336). 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.

The impact of high-intensity interval training on ventricular remodeling in patients with a recent acute myocardial infarction-A randomized training intervention pilot study.

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 ˙ O 2 peak 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 ˙ O 2 at the first ventilatory threshold ( V ˙ O 2 VT1) were calculated. left ventricular (LV) structural and functional echocardiographic parameters including myocardial strain imaging were assessed. RESULTS: V ˙ O 2 peak and OUES improved solely in the HIIT group (P < .05 for group/time, respectively). There was a significant training effect for the improvement of peak work load in both groups (P < .05). O2 pulse and V ˙ O 2 at VT1 both improved only in the HIIT group (P < .05 for time, no interaction). HIIT improved radial strain and pulsed-wave tissue Doppler imaging derived e' (P < .05 for time, no interaction). Cardiac biomarkers did not change in either group. CONCLUSIONS: In post-AMI patients, HIIT lead to significant improvements in prognostic CPET parameters compared to usual care. HIIT was associated with favorable ventricular remodeling regarding certain echocardiographic parameters of LV function.

Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis in Women: Clinical Characteristics and Outcomes.

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.

The Role of Biomarkers in Decreasing Risk of Cardiac Toxicity after Cancer Therapy.

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.

Ivabradine for the treatment of chronic heart failure.

Several studies have underlined the beneficial effects of a lower heart rate on mortality in patients with chronic heart failure and reduced ejection fraction. In clinical practice, achieving a heart rate ≤70 bpm with beta-blockers is not always possible. In this context, the more recent guidelines added ivabradine to the management of those patients if heart rate remains ≥70 bpm in sinus rhythm and symptoms persist despite treatment with an evidence-based or maximum tolerated dose of a beta-blocker, an angiotensin converting enzyme inhibitor or angiotensin-receptor blocker, and a mineralocorticoid receptor antagonist. Ivabradine is a well-tolerated, safe and effective treatment option with the objective to improve prognosis, left ventricular structure and function, exercise tolerance and quality of life. Accordingly, the following article will evaluate the benefits of a combination of the currently recommended pharmacological therapy in chronic heart failure with the selective heart rate reducing agent ivabradine.

Impact of Serial B-Type Natriuretic Peptide Changes for Predicting Outcome in Asymptomatic Patients With Aortic Stenosis.

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.

Prediction of new onset of resting pulmonary arterial hypertension in systemic sclerosis.

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.

Exercise Lowers Plasma Angiopoietin-Like 2 in Men with Post-Acute Coronary Syndrome.

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<0.05), but did not significantly affect endothelial function, in both men and women. In contrast, exercise reduced angptl2 levels only in men (-26±7%, p<0.05), but unexpectedly not in women (+30±16%), despite similar initial levels in both groups. Exercise reduced hs-CRP levels in men but not in women. In men, levels of angptl2, but not of hs-CRP, reached at the end of the training program were negatively correlated with VO2peak (r = -0.462, p = 0.012) and with endothelial function (r = -0.419, p = 0.033) measured at baseline: better initial cardiopulmonary fitness and endothelial function correlated with lower angptl2 levels after exercise. Pre-exercise angptl2 levels were lower if left ventricular ejection time was long (p<0.05) and the drop in angptl2 induced by exercise was greater if the cardiac output was high (p<0.05). In conclusion, in post-ACS men, angptl2 levels are sensitive to chronic exercise training. Low circulating angptl2 reached after training may reflect good endothelial and cardiopulmonary functions.

Brain Natriuretic Peptide Levels and the Occurrence of Subclinical Pulmonary Edema in Healthy Lowlanders at High Altitude.

BACKGROUND: 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). METHODS: 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. RESULTS: Heart rate, Lake Louise Score (P < 0.0001) and blood pressure (P = 0.037) increased during ascension; oxygen saturation decreased (P < 0.0001). BNP increased (40.7 ± 16.8 vs 19.7 ± 3.04 pg/mL; P < 0.01) after the summit, as did ultrasound lung comet count throughout ascension (P < 0.0001), 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). CONCLUSION: 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.