Valentina Labate

Heart rate recovery after the 6 min walk test rather than distance ambulated is a powerful prognostic indicator in heart failure with reduced and preserved ejection fraction: a comparison with cardiopulmonary exercise testing

Heart rate recovery (HRR) appears to be a robust prognostic marker in heart failure (HF). When using the 6 min walk test (6MWT) in HF, distance ambulated is generally the reference prognostic variable. We hypothesized that HRR after the 6MWT would be a better prognostic measure than distance ambulated.

Cardiopulmonary exercise testing reflects similar pathophysiology and disease severity in heart failure patients with reduced and preserved ejection fraction.

Background We are unaware of any previous investigation that has compared the relationship of key cardiopulmonary exercise testing (CPX) variables to various measures of pathophysiology between heart failure-reduced ejection fraction (HFrEF) and HF-preserved ejection fraction (HFpEF) cohorts that are well matched with respect to baseline characteristics and their exercise response, which is the purpose of the present study. Methods Thirty-four patients with HFpEF were randomly matched to 34 subjects with HFrEF according to age and sex as well as peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), and exercise oscillatory ventilation (EOV). In addition to CPX, patients also underwent echocardiography with tissue Doppler imaging (TDI) and assessment of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Results When matched for age, sex, and CPX variables, the HFrEF and HFpEF cohorts had similar echocardiography with TDI and NT-proBNP values, indicating comparable disease severity. In addition, the correlations between key CPX measures (peak VO2 and VE/VCO2 slope) and echocardiography with TDI and NT-proBNP measures were similar between HFrEF and HFpEF groups. Of note, the correlation between the VE/VCO2 slope and pulmonary artery systolic pressure and NT-proBNP was highly significant in both groups (r ≥ 0.65, p < 0.01). Moreover, subjects with EOV in both groups had a significantly higher PASP (∼47 vs. ∼35 mmHg, p < 0.05). Conclusions The results of the current study indicate CPX equally represents disease severity in HFrEF and HFpEF patients. This is a novel finding supporting the key role of CPX in the clinical follow-up of HF patients irrespective of LVEF and cardiac phenotype.

Cardiopulmonary Exercise Testing in Heart Failure.

A growing body of literature has underscored the value of ventilatory gas exchange techniques during exercise testing (commonly termed cardiopulmonary exercise testing, or CPX) and their applications in the management of patients with heart failure (HF). The added precision provided by this technology is useful in terms of understanding the physiology and mechanisms underlying exercise intolerance in HF, quantifying the response to therapy, evaluating disability, making activity recommendations, and quantifying the response to exercise training. Importantly, a wealth of data has been published in recent years on the prognostic utility of CPX in patients with HF. These studies have highlighted the concept that indices of ventilatory inefficiency, such as the VE/VCO2 slope and oscillatory breathing, are particularly powerful in stratifying risk in HF. This article provides an overview of the clinical utility of CPX in patients with HF, including the applications of ventilatory inefficiency during exercise, the role of the pulmonary system in HF, respiratory muscle performance (RMP), and the application of CPX as part of a comprehensive clinical and exercise test evaluation.

Prevalence and characterization of exercise oscillatory ventilation in apparently healthy individuals at variable risk for cardiovascular disease: A subanalysis of the EURO-EX trial

Introduction There has been a greater appreciation of several variables obtained by cardiopulmonary exercise testing (CPX). Exercise oscillatory ventilation (EOV) is a CPX pattern that has gained recognition as an ominous marker of poor prognosis in cardiac patients. The purpose of the present study is to characterize whether such an abnormal ventilatory pattern may also be detected in apparently healthy subjects and determine its clinical significance. Methods The study involved 510 subjects (mean age 60 ± 14 years; 49% male) with a broad cardiovascular (CV) risk factor profile who underwent CPX. Results The population was divided into two groups according to the presence (17%) or absence of EOV. Subjects with EOV were significantly older and a higher percentage was female. Risk factor profile and medication use was significantly different between subgroups, indicating subjects with EOV had a worse CV risk factor profile and were prescribed CV-focused preventive medications at a significantly higher frequency. Subjects with EOV had comparatively poorer CPX performance and gas exchange phenotype. Multivariate binary logistic regression analysis found being female was the strongest predictor of EOV (odds ratio: 2.77, 95% confidence interval (CI): 1.66-4.61, p < 0.001). A diagnosis of diabetes (odds ratio: 2.40, 95% CI: 1.34–4.15.2, p < 0.001) added significant value for predicting EOV and was retained in the regression. The likelihood for EOV for subjects who were female and diagnosed with diabetes was 3.71 (95% CI 1.88–7.30, p < 0.001). Conclusions This is the first study to examine EOV prevalence and characterization in apparently healthy persons with results supporting an in-depth definition of abnormal exercise phenotypes.

Exercise oscillatory breathing and NT-proBNP levels in stable heart failure provide the strongest prediction of cardiac outcome when combining biomarkers with cardiopulmonary exercise testing.

BACKGROUND N-Terminal pro-brain natriuretic peptide (NT-proBNP) and cardiopulmonary exercise testing (CPET)-derived variables are gold standards for assessing prognosis in heart failure (HF) patients. We sought to refine cardiac events prediction by performing a combined analysis of NT-proBNP with markers of exercise ventilatory efficiency. METHODS AND RESULTS A total of 260 stable HF patients underwent measurements of plasma NT-proBNP levels before, at peak exercise, and at 1-minute CPET recovery phase along with peak oxygen uptake (VO(2)), ventilation to CO(2) production (VE/VCO(2)) slope, and exercise periodic breathing (EPB) determinations. After a median follow-up period of 20.6 months, there were 54 cardiac-related deaths. Univariate analysis including NT-proBNP at rest, at peak exercise, and at 1 minute recovery, peak VO(2), VE/VCO(2) slope, and EPB showed NT-proBNP to be the strongest independent predictor with equivalent performance for rest, peak, and recovery levels. Thus, only NT-proBNP at rest was considered (Harrel C 0.783, 95% confidence interval [CI] 0.722-0.844) with VE/VCO(2) slope (Harrel C 0.720, 95% CI 0.646-0.794), EPB (Harrel C 0.685, 95% CI 0.619-0.751), and peak VO(2) (Harrel C 0.618, 95% CI 0.533-0.704). With bivariate stepwise analyses, NT-proBNP along with EPB emerged as the strongest prognosticators (Harrel C 0.800, 95% CI 0.737-0.862). CONCLUSIONS In the refinement for robust outcome predictors in HF patients, NT-proBNP levels together with EPB led to the most powerful definition. VE/VCO(2) slope and peak VO(2) did not provide any prognostic adjunct. A biomarker/CPET approach seems very promising to warrant the continuous implementation in the prognostic work-up of HF patients.

Predictors of abnormal heart rate recovery in patients with heart failure reduced and preserved ejection fraction

Background Heart rate recovery (HRR) is becoming an important prognostic maker in heart failure (HF), but very little is known about the underlying mechanisms responsible for its clinical efficacy. Therefore, we examined echocardiographic and exercise (submaximal and maximal) characteristics to gain a better appreciation of HRR and factors responsible for the development of abnormal HRR in patients with both heart failure reduced ejection fraction (HFrEF) and heart failure preserved ejection fraction (HFpEF). Methods Cardiopulmonary exercise testing (CPX), a 6-minute walk test (6MWT), and resting 2D echocardiography were randomly performed in 240 HF patients (200 HFrEF, 40 HFpEF) after which HRR was measured. HRR was defined as the difference between heart rate at peak exercise and 1 minute following test termination. Results Bivariate correlation analyses found significant relationships among most CPX and 6MWT measurements with the highest correlations between 6MWT HRR and 6MWT peak HR (r = 0.65; p < 0.001) and CPX HRR and CPX HRreserve (r = 0.63; p < 0.001). The relationship between 6MWT HRR and CPX HRR was very good (r = 0.91; p < 001). Multivariate logistic regression of submaximal and maximal exercise found 6MWT peak HR and exercise oscillatory ventilation (EOV), respectively, were the strongest predictors (p < 0.001) of abnormal HRR. The E/E′ was a significant predictor (p < 0.001) of abnormal HRR, but EOV was the strongest predictor of abnormal HRR (OR = 6.5). Conclusions HRR after both CPX and the 6MWT is significantly related to many exercise and echocardiographic measures with the most significant predictors of abnormal HRR being related to indices of cardiorespiratory performance in patients with HFrEF and HFpEF.

Treatment for Pulmonary Hypertension of Left Heart Disease

Opinion statementPulmonary hypertension (PH) secondary to left heart disease is a largely underestimated target of therapy. Except for a specific focus on PH consequences in patients with advanced heart failure (HF) receiving a left ventricular mechanical assist device or candidates for transplantation, prevention and treatment of initial subclinical forms of PH are not considered a priority in the management of this chronic disease population. Nonetheless, there is recent growing evidence supporting a clinical and prognostic role of PH in the elderly and in HF with preserved ejection fraction (pEF). Studies have defined PH-HFpEF as a new entity typically defining the evolving nature of disease. Although the prevalence of PH in these populations is not well-defined, the potential for effective pharmacological approaches that might impact the natural history of the disease starting from earlier stages is promising. However, it should be recognized that pharmacological studies performed to date with traditional pulmonary vasodilators in cohorts with HF and left-sided PH have not been positive, primarily because of concomitant systemic hypotension and hepatic side effects. This evidence along with the lack of studies specifically performed in the elderly and HFpEF often lead Guidelines to give neutral recommendations or even arbitrary assumptions. Recent availability of selective well-tolerated pulmonary vasodilators, such as phosphodiesterase type 5 (PDE5) inhibitors, however, seem to offer a solid background for treating left-sided PH at both early and later stages of the disease process.

Mitral regurgitation in heart failure: insights from CPET combined with exercise echocardiography

Aims In heart failure patients with reduced ejection fraction (HFrEF), exercise‐induced functional mitral regurgitation (MR) may affect functional capacity and outcome. We sought to study functional and cardiac phenotypes of HFrEF patients according to the MR degree. Methods and results We performed rest and exercise echocardiography (Ex‐Echo), simultaneously combined with cardiopulmonary exercise test (CPET), in 102 HFrEF patients, identifying 3 groups: non‐severe (ERO <20 mm2) MR (group A), exercise‐induced severe (ERO ≥20 mm2) MR (group B), and rest severe MR (group C). Patients were tracked for the composite end point of death and heart failure hospitalization. Group B (ERO: rest= 14 ± 5 mm2, Ex= 28 ± 6 mm2; P = < 0.001) had a functional impairment (workload = 56 ± 21 vs. 50 ± 17 watts, P = 0.42; peak VO2 = 11.8 ± 3.2 vs. 11.5 ± 3.0 mL/Kg/min, P = 0.70) similar to Group C (ERO: rest = 29 ± 7 mm2, Ex = 42 ± 7 mm2, P = < 0.001), associated with comparable advanced left ventricle remodelling (end diastolic indexed volume = 107 ± 34 vs. 115 ± 30 mL/m2, P = 0.27), characterized by exercise‐induced pulmonary hypertension (PH) (Ex systolic pulmonary pressures = 63 ± 16 mmHg). Group C showed the worse cardiac phenotype (right ventricle dilatation, dysfunction, and rest PH) with severe ventilatory impairment (VE/VCO2 = 41.2 ± 11) compared with Groups A and B. Moreover, Group C had the higher rate of death and HF hospitalization. Conclusions In HFrEF patients, severe dynamic MR produces functional limitation similar to rest severe MR, characterized by dynamic PH. Rest severe MR reflects the most advanced bi‐ventricular remodelling associated with rest PH, the most unfavourable ventilatory profile, and the worst mid‐term outcome.

Pulmonary Hypertension in Heart Failure Patients: Pathophysiology and Prognostic Implications

Pulmonary hypertension (PH) due to left heart disease (LHD), i.e., group 2 PH, is the most common reason for increased pressures in the pulmonary circuit. Although recent guidelines incorporate congenital heart disease in this classification, left-sided heart diseases of diastolic and systolic origin including valvular etiology are the vast majority. In these patients, an increased left-sided filling pressure triggers a multistage hemodynamic evolution that ends into right ventricular failure through an initial passive increase in pulmonary artery pressure complicated over time by pulmonary vasoconstriction, endothelial dysfunction, and remodeling of the small-resistance pulmonary arteries. Regardless of the underlying left heart pathology, when present, PH-LHD is associated with more severe symptoms, worse exercise tolerance, and outcome, especially when right ventricular dysfunction and failure are part of the picture. Compared with group 1 and other forms of pulmonary arterial hypertension, PH-LHD is more often seen in elderly patients with a higher prevalence of cardiovascular comorbidities and most, if not all, of the features of metabolic syndrome, especially in case of HF preserved ejection fraction. In this review, we provide an update on current knowledge and some potential challenges about the pathophysiology and established prognostic implications of group 2 PH in patients with HF of either preserved or reduced ejection fraction.

Past, Present, and Future Rehabilitation Practice Patterns for Patients with Heart Failure. The European Perspective.

The recent European Society of Cardiology position paper strongly advises participation of patients with stable heart failure (HF) in structured exercise training (ET) programs, and in most recent years considerable efforts have been put into standardization of exercise prescription. Up to now, 3 ET modalities are proposed for HF populations with variable combinations and extent of effects: (1) endurance aerobic (continuous and interval); (2) strength/resistance; (3) respiratory. Irrespective of ET modalities, most of the studies have clearly demonstrated significant improvements in exercise physiology (ie, oxygen consumption, muscle function, and ventilation), quality of life, and left ventricular function.