The Role of Galectin-3 in Heart Failure-The Diagnostic, Prognostic and Therapeutic Potential-Where Do We Stand?

Heart failure (HF) is a clinical syndrome with high morbidity and mortality, and its prevalence is rapidly increasing. Galectin-3 (Gal-3) is an important factor in the pathophysiology of HF, mainly due to its role in cardiac fibrosis, inflammation, and ventricular remodeling. Fibrosis is a hallmark of cardiac remodeling, HF, and atrial fibrillation development. This review aims to explore the involvement of Gal-3 in HF and its role in the pathogenesis and clinical diagnostic and prognostic significance. We report data on Gal-3 structure and molecular mechanisms of biological function crucial for HF development. Over the last decade, numerous studies have shown an association between echocardiographic and CMR biomarkers in HF and Gal-3 serum concentration. We discuss facts and concerns about Gal-3's utility in acute and chronic HF with preserved and reduced ejection fraction for diagnosis, prognosis, and risk stratification. Finally, we present attempts to use Gal-3 as a therapeutic target in HF.

Subclinical Dysfunction of Left Atrial Compliance after Cryoballoon versus Radiofrequency Ablation for Paroxysmal Atrial Fibrillation.

It has been suggested that cryoballoon (CB) ablation for paroxysmal atrial fibrillation (PAF) may lead to more extensive left atrial (LA) injury than radiofrequency (RF) ablation; however, results are conflicting. We sought to address this issue using modern echocardiographic techniques estimating the LA function after successful CB and RF ablation for PAF. A total of 90 patients (66% males, mean age 57 ± 10 years) successfully treated (no AF recurrences confirmed in serial 4-7 day ECG Holter monitoring) with RF (51%) or CB (49%) ablation for PAF were retrospectively studied. Echocardiography with speckle tracking (STE) was performed before and 12 months after the procedure. The peak longitudinal LA strain (LAS) and strain rate (LASR) during the reservoir (r), conduit (cd), and contraction (ct) phases were measured in sinus rhythm. Analysis of covariance was applied to compare changes in the echocardiographic parameters over time with the baseline measurements as covariance and the type of ablation as the factor. The parallelism of the slopes of the covariance was tested. The LA diameter decreased (38.3 ± 4.1 mm vs. 36.8 ± 3.6 mm, p < 0.001) in the whole study group at 12 months after ablation. The LASRr and LASRcd increased (1.1 ± 0.3 s-¹ vs. 1.3 ± 0.3 s-¹, p < 0.001 and 1.1 ± 0.3 s-¹ vs. 1.2 ± 0.3 s-¹, p < 0.001, respectively) whereas other LA strain parameters remained unchanged in the whole study group at 12 months after ablation. In the analysis of LA function at 12 months after the procedure regarding the mode of ablation, the worsening of parameters reflecting LA compliance was observed in patients with better pre-served baseline values in the CB ablation subgroup. For baseline LAScd >28%, the difference ΔCB - ΔRF was -7.6 (11.7; -3.4), p < 0.001, and for baseline LAScd >16%, ΔCB - ΔRF was -1.8 (-3.2; -0.4), p = 0.014. The traditional Doppler-derived parameter e' showed the same trend-for baseline e' ≥12 cm/s, ΔCB - ΔRF was -1.7 (-2.8; -0.6), p = 0.003. We conclude that worsening of parameters reflecting LA compliance was observed 12 months after CB ablation compared to RF ablation for PAF in patients who underwent a successful procedure and had better-preserved baseline LA function. This might suggest subclinical dysfunction of LA after the CB ablation procedure. The clinical significance of these findings warrants further investigations.

Mechanisms of Exercise Capacity Improvement after Cardiac Rehabilitation Following Myocardial Infarction Assessed with Combined Stress Echocardiography and Cardiopulmonary Exercise Testing.

Cardiac rehabilitation (CR) is indicated in all patients after acute myocardial infarction (AMI) to improve prognosis and exercise capacity (EC). Previous studies reported that up to a third of patients did not improve their EC after CR (non-responders). Our aim was to assess the cardiac and peripheral mechanisms of EC improvement after CR using combined exercise echocardiography and cardiopulmonary exercise testing (CPET-SE). The responders included patients with an improved EC assessed as a rise in peak oxygen uptake (VO2) ≥ 1 mL/kg/min. Peripheral oxygen extraction was calculated as arteriovenous oxygen difference (A-VO2Diff). Out of 41 patients (67% male, mean age 57.5 ± 10 years) after AMI with left ventricular ejection fraction (LVEF) ≥ 40%, 73% improved their EC. In responders, peak VO2 improved by 27% from 17.9 ± 5.2 mL/kg/min to 22.7 ± 5.1 mL/kg/min, p < 0.001, while non-responders had a non-significant 5% decrease in peak VO2. In the responder group, the peak exercise heart rate, early diastolic myocardial velocity at peak exercise, LVEF at rest and at peak exercise, and A-VO2Diff at peak exercise increased, the minute ventilation to carbon dioxide production slope decreased, but the stroke volume and cardiac index were unchanged after CR. Non-responders had no changes in assessed parameters. EC improvement after CR of patients with preserved LVEF after AMI is associated with an increased heart rate response and better peripheral oxygen extraction during exercise.

Combined use of stress echocardiography and cardiopulmonary exercise testing to assess exercise intolerance in patients treated for acute myocardial infarction.

Exercise intolerance after acute myocardial infarction (AMI) is a predictor of worse prognosis, but its causes are complex and poorly studied. This study assessed the determinants of exercise intolerance using combined stress echocardiography and cardiopulmonary exercise testing (CPET-SE) in patients treated for AMI. We prospectively enrolled patients with left ventricular ejection fraction (LV EF) ≥40% for more than 4 weeks after the first AMI. Stroke volume, heart rate, and arteriovenous oxygen difference (A-VO2Diff) were assessed during symptom-limited CPET-SE. Patients were divided into four groups according to the percentage of predicted oxygen uptake (VO2) (Group 1, <50%; Group 2, 50-74%; Group 3, 75-99%; and Group 4, ≥100%). Among 81 patients (70% male, mean age 58 ± 11 years, 47% ST-segment elevation AMI) mean peak VO2 was 19.5 ± 5.4 mL/kg/min. A better exercise capacity was related to a higher percent predicted heart rate (Group 2 vs. Group 4, p <0.01), higher peak A-VO2Diff (Group 1 vs. Group 3, p <0.01) but without differences in stroke volume. Peak VO2 and percent predicted VO2 had a significant positive correlation with percent predicted heart rate at peak exercise (r = 0.28, p = 0.01 and r = 0.46, p < 0.001) and peak A-VO2Diff (r = 0.68, p <0.001 and r = 0.36, p = 0.001) but not with peak stroke volume. Exercise capacity in patients treated for AMI with LV EF ≥40% is related to heart rate response during exercise and peak peripheral oxygen extraction. CPET-SE enables non-invasive assessment of the mechanisms of exercise intolerance.

Chronotropic Incompetence Limits Aerobic Exercise Capacity in Patients Taking Beta-Blockers: Real-Life Observation of Consecutive Patients.

BACKGROUND: Chronotropic incompetence in patients taking beta-blockers is associated with poor prognosis; however, its impact on exercise capacity (EC) remains unclear. METHODS: We analyzed data from consecutive patients taking beta-blockers referred for cardiopulmonary exercise testing to assess EC. Chronotropic incompetence was defined as chronotropic index (CI) ≤ 62%. RESULTS: Among 140 patients all taking beta-blockers (age 61 ± 9.7 years; 73% males), 64% with heart failure, chronotropic incompetence was present in 80.7%. EC assessed as peak oxygen uptake was lower in the group with chronotropic incompetence, 18.3 ± 5.7 vs. 24.0 ± 5.3 mL/kg/min, p < 0.001. EC correlated positively with CI (ß = 0.14, p < 0.001) and male gender (ß = 5.12, p < 0.001), and negatively with age (ß = -0.17, p < 0.001) and presence of heart failure (ß = -3.35, p < 0.001). Beta-blocker dose was not associated with EC. Partial correlation attributable to CI accounted for more than one-third of the variance in EC explained by the model (adjusted R2 = 59.8%). CONCLUSIONS: In patients taking beta-blockers, presence of chronotropic incompetence was associated with lower EC, regardless of the beta-blocker dose. CI accounted for more than one-third of EC variance explained by our model.

Comprehensive cardiac rehabilitation as the keystone in the secondary prevention of cardiovascular disease.

Comprehensive cardiac rehabilitation (CR) is a mainstay of the secondary prevention of cardiovascular disease. In the European Society of Cardiology guidelines, comprehensive cardiovascular rehabilitation has the highest class of recommendation and level of evidence as an effective method for the treatment of patients with ST-segment elevation myocardial infarction, after myocardial revascularization, with chronic coronary syndrome, for CVD prevention in clinical practice, and in patients with heart failure (HF). This document presents an expert opinion of the Cardiac Rehabilitation and Exercise Physiology Section of the Polish Cardiac Society concerning the definition, goals, target population, organization of rehabilitation services, standard clinical indications and methods of implementation. Moreover, it describes psychosocial risk factors influencing the course of CR and secondary prevention of cardiovascular disease in patients undergoing CR. Comprehensive CR is as a process that should be implemented as soon as possible, continued without interruption, and consist of multiple stages. Moreover, it should be tailored to the individual clinical situation and should be accepted by the patient and their family, friends, and caregivers.

Galectin-3 is related to right ventricular dysfunction in heart failure patients with reduced ejection fraction and may affect exercise capacity.

Galectin-3 is a biomarker of fibrosis, inflammation and oxidative stress, and its role in heart remodelling and exercise intolerance has not been conclusively proven in heart failure (HF) patients with reduced ejection fraction (rEF). We prospectively assessed 67 consecutive patients with symptomatic HF and left ventricular (LV) EF ≤ 35% during optimal medical therapy, with a mean serum galectin-3 concentration of 15.3 ± 6.4 and a median of 13.5 ng/mL. The group with galectin-3 concentrations greater than or equal to the median had significantly worse right ventricular (RV) systolic function parameters (s', TAPSE), higher pulmonary artery systolic pressure, more advanced tricuspid regurgitation and lower RV-to-pulmonary circulation coupling index, while no significant differences were found in LV parameters. Moreover, this group achieved significantly lower parameters in cardiopulmonary exercise testing. Significant negative correlations were found between galectin-3 concentration and RV parameters and exercise capacity parameters and have persisted after adjustment for glomerular filtration rate, but not all of them have persisted after adjustment for NT-proBNP. Multivariate regression analysis revealed that TAPSE (ß coefficient: - 0.605; p < 0.001) and heart rate at peak exercise (ß coefficient: - 0.98; p = 0.009) were independently related to galectin-3 concentration. Elevated galectin-3 concentration in patients with HFrEF might indicate concomitant RV dysfunction and exercise intolerance.

Cardiopulmonary exercise testing in adult cardiology: expert opinion of the Working Group of Cardiac Rehabilitation and Exercise Physiology of the Polish Cardiac Society.

Cardiopulmonary exercise testing (CPET) is an important diagnostic tool in contemporary clinical practice. This document presents an expert opinion from the Working Group on Cardiac Rehabilitation and Exercise Physiology of the Polish Cardiac Society concerning the indications, performance technique, and interpretation of results for CPET in adult cardiology. CPET is an electrocardiographic exercise test expanded with exercise evaluation of ventilatory and gas exchange parameters. It allows for a global assessment of the exercise performance including the pulmonary, cardiovascular, hematopoietic, neuropsychological, and musculoskeletal systems. It provides a noninvasive dynamic evaluation during exercise and is a reference modality for exercise capacity assessment. Moreover, it allows the measurement of numerous prognostic parameters. It is useful in cardiology, pulmonology, oncology, perioperative assessment, rehabilitation as well as in sports medicine and in the evaluation of healthy people. This test not only helps to diagnose the causes of exercise intolerance but also supports the evaluation of the treatment. New opportunities are offered by combining CPET with imaging such as exercise stress echocardiography. These tests are complementary and synergistic in their diagnostic and prognostic strength.

Electrocardiographic exercise testing in adults: performance and interpretation. An expert opinion of the Polish Cardiac Society Working Group on Cardiac Rehabilitation and Exercise Physiology.

Electrocardiographic (ECG) exercise stress test has been a major diagnostic test in cardiology for several decades. Ongoing technological advances that have led to a wide use of imaging techniques and development of new guidelines have called for a revised and updated approach to the technique and interpretation of the ECG exercise testing. The present document outlines an expert opinion of the Polish Cardiac Society Working Group on Cardiac Rehabilitation and Exercise Physiology regarding the performance and interpretation of ECG exercise testing in adults. We discussed technical requirements and necessary equipment for the exercise testing laboratory as well as healthcare personnel competencies necessary to supervise ECG exercise testing and fully interpret test findings. Broad indications for ECG exercise testing include diagnostic assessment of coronary artery disease (CAD), including pre-test probability of CAD, evaluation of functional disease severity and risk strati- fication in patients with established CAD, assessment of response to treatment, evaluation of exercise-related symptoms and exercise capacity, patient evaluation before exercise training/cardiac rehabilitation, and risk stratification prior to non-cardiac surgery. ECG exercise testing is safe if indications and contraindications are observed, testing is appropriately monitored, and indications for test termination are clearly established. The exercise protocol should be adjusted to the expected exercise capacity of a patient so as to limit the duration of exercise to 8-12 min. Clinical, haemodynamic, and ECG response to exercise is evaluated during the test. The test report should include information about the exercise protocol used, reason for test termination, perceived exertion, presence/severity of anginal symptoms, peak exercise capacity or tolerated workload in relation to the predicted exercise capacity, heart rate response, and the presence or absence of ST-T changes. The test report should conclude with a summary including clinical and ECG assessment.

Echocardiographic predictors of exercise intolerance in patients with heart failure with severely reduced ejection fraction.

Decreased exercise capacity (EC) is an established predictor of cardiac and all-cause mortality in patients with chronic heart failure (HF). No correlation has been found between EC and left ventricular (LV) ejection fraction. Moreover, data about the effect of right ventricular (RV) function on EC in HF with severe LV dysfunction are limited and contradictory. In this study, we aimed to investigate the relationship between EC and myocardial mechanics in patients with HF with reduced ejection fraction.Consecutive patients with symptomatic HF and LV ejection fraction ≤35% were prospectively assessed. All patients were evaluated with enhanced echocardiography. A symptom-limited treadmill cardiopulmonary exercise test (CPX) was performed within 24-hour interval. Patients were stratified into 4 groups according to their EC defined by Weber's classification. Prognosis of EC, expressed as oxygen uptake at peak exercise (peak VO2), was evaluated in multivariate linear regression analysis model.Sixty-seven patients with New York Heart Association classes II to III and a mean LV ejection fraction of 26 ±â€Š7% were enrolled. A wide range of peak VO2 was observed in CPX with patient exercise performance distributed to all classes according to Weber's classification. Significant differences were found in RV systolic and diastolic functions between groups with different classes of EC: RV peak systolic myocardial velocity (S') (P < .001), tricuspid annular plane systolic excursion (TAPSE) (P = .003), RV E' (P = .003). In patients with functional decline, systolic pulmonary artery pressure (PASP) was higher (P = .029) and TAPSE/PASP ratio was lower (P = .006). No significant differences were found in LV diameter, systolic and diastolic function, and degree of mitral regurgitation. Thirty three patients with RV systolic dysfunction showed lower peak VO2 and oxygen uptake at anaerobic threshold (P = .008, P = .006, respectively), shorter exercise time (P = .003), and lower systolic blood pressure (P = .01) than in patients with normal RV systolic function. Logistic multivariate linear regression analysis with stepwise inclusion and exclusion revealed that gender, RV S', and RV free wall strain were independent predictors of peak VO2.RV function, assessed as S' and free wall strain, was independently related to EC, measured using CPX, in patients with HF and severe LV systolic dysfunction.

Acute Hemodynamic and Tissue Effects of Cryoballoon Ablation on Pulmonary Vessels: The IVUS-Cryo Study.

BACKGROUND: Cryoballoon-based pulmonary vein isolation (CB-PVI) has been widely used for the treatment of atrial fibrillation. Although generally safe and effective, the procedure may be associated with pulmonary vein (PV) stenosis and bronchial or esophageal injury. The mechanisms leading to these complications have not been studied in detail. Our aim was to examine acute effects of cryoballoon on the pulmonary vessel and right heart pressures as well as PV wall morphology. METHODS AND RESULTS: In 8 patients (5 men, mean age 55±14 years) undergoing CB-PVI, pressure in each PV was measured by catheter located inside the PV directly before and after CB-PVI. The right atrial, right ventricular, and pulmonary artery pressures as well as pulmonary arterial wedge capillary pressure in the pulmonary artery branch corresponding to target PV were also measured. Morphological changes in PVs were assessed using intravascular ultrasonography.There were no significant differences in PV pressures before and after ablation. The pulmonary arterial wedge capillary pressure significantly increased during cryoapplication (left superior: 20±10 versus 29±8.5 mm Hg, P=0.004; left inferior: 24±10 versus 32±6 mm Hg, P=0.012; right superior: 25±9 versus 35±10 mm Hg, P=0.002; right inferior: 24±10 versus 37±12 mm Hg, P=0.0036). The right atrial and pulmonary artery pressures increased significantly after CB-PVI (9±6 versus 13±8 mm Hg, P=0.004, and 20±9 versus 24±10 mm Hg, P=0.048, respectively). Intravascular ultrasonography showed acute edema and dissection-like changes causing relative lumen narrowing in 90% of PVs. CONCLUSIONS: CB-PVI causes significant rise in pulmonary artery and right atrial pressures as well as PV wall damage. The clinical significance of these findings warrants further investigations.

Right ventricular systolic function as a marker of prognosis after ST-elevation inferior myocardial infarction 5-year follow-up.

BACKGROUND: There is scarce data about clinical value of right ventricular (RV) systolic function assessed in pre-discharge transthoracic echocardiography for predicting long-term prognosis in patients with inferior ST-elevation myocardial infarction (MI). METHODS: The aim of this study was to assess correlations of RV function parameters in patients after inferior ST-elevation MI with preserved or mildly impaired left ventricular ejection fraction with prognosis during 5-year follow-up. Primary endpoint was death from any cause or unscheduled hospitalization for cardiac causes (unstable angina/MI, percutaneous coronary intervention/coronary artery bypass grafting due to progression of coronary artery disease, heart failure exacerbation or pacemaker implantation), secondary endpoints were all listed above components analyzed separately. RV systolic function was measured with pulsed tissue Doppler as systolic myocardial velocity at the basal segment of RV free wall in the acute phase and pre-discharge echocardiography. RESULTS: Follow-up was conducted in 86 consecutive patients (mean age 61±10years, 74% males). Multivariate regression analysis revealed that only RV systolic function in pre-discharge echocardiography correlated independently with the primary endpoint (OR 0.56, 95% CI 0.34-0.92, p=0.02). A positive predictive value of 44% and a negative predictive value of 83% (sensitivity 80%, specificity 49%, AUC 0.7) for predicting the primary endpoint was established for RV systolic myocardial velocity<13cm/s in pre-discharge echocardiography. CONCLUSIONS: In patients after inferior wall ST-elevation MI with preserved or slightly impaired LV systolic function, pre-discharge RV systolic dysfunction correlated independently with worse long-term prognosis.

Right ventricular dysfunction and exercise capacity after inferior (posterior) wall acute myocardial infarction.

Tissue Doppler echocardiography is a novel technique that can be used to diagnose right ventricular (RV) systolic dysfunction. Until recently, there have been no data on the influence of tissue Doppler-derived RV systolic dysfunction on exercise capacity after inferior (posterior) myocardial infarction (MI). We studied 90 consecutive patients (76% men, mean age 61 ± 10 years) with first inferior ST-segment elevation MI and left ventricular ejection fraction ≥45%. RV systolic dysfunction was defined as RV systolic myocardial velocity <11.5 cm/s at the basal segment of the RV free wall assessed by pulse tissue Doppler. Patients were categorized as with or without RV systolic dysfunction (RV systolic myocardial velocity 9.34 ± 1.36 and 13.74 ± 1.58 cm/s, respectively). A cardiopulmonary exercise test was performed before or soon after discharge (day 14 ± 10). Patients with RV systolic dysfunction had lower oxygen consumption assessed as percent predicted oxygen uptake in liters per minute and milliliters per kilogram per minute at their anaerobic threshold (61 ± 11% vs 69 ± 17%, p = 0.007; 53 ± 12% vs 61 ± 19%, p = 0.012, respectively) and at peak exercise (71 ± 12% vs 83 ± 16%, p = 0.0001; 62 ± 14% vs 74 ± 21%, p = 0.002, respectively). Multivariate regression analysis revealed that the following independent factors negatively influenced exercise capacity: RV systolic dysfunction, female gender, age, lower body mass index, current smoking, and maximal troponin I concentration. In conclusion, we found decreased exercise capacity in patients with systolic RV dysfunction assessed by pulse tissue Doppler in patients with inferior (posterior) wall acute MI despite preserved left ventricular function.