Left atrial strain in acute heart failure: clinical and prognostic insights.

AIMS: In acute heart failure (AHF), the consequences of impaired left atrial (LA) mechanics are not well understood. We aimed to define the clinical trajectory of LA mechanics by left atrial strain (LAS) analysis. METHODS AND RESULTS: Eighty-five consecutive AHF patients with reduced, mildly reduced, and preserved left ventricular ejection fraction (LVEF) were enrolled in the LAS-AHF trial and underwent LA mechanics analysis by speckle tracking echocardiography. Seventy-seven patients were followed-up (FU) at 6 and 12 months. At hospital admission, discharge, 6 and 12 months post-discharge, LA reservoir function (LAS), LA pump strain, LAVi, LA stiffness, indicators of right ventricular (RV) and left ventricular (LV) function, congestion indexes (B lines, inferior vena cava, X-ray congestion score index), and biomarkers (NT-pro-BNP) were measured. The primary outcome was time to first event of re-hospitalization, worsening HF, or cardiovascular death. From admission to discharge, RV function significantly improved after decongestion, whereas no significant differences were observed in LA dynamics and LV function. In sinus rhythm patients with mild or no mitral regurgitation, decongestion was associated with a significant improvement of LAS and LA pump strain rate during hospitalization. At 12 months, 24 CV events occurred and lack of LAS improvement at 12 months FU emerged as the most powerful predictor followed by NT-pro-BNP. Kaplan-Meier curves showed a better survival for LAS >16%, improvement of LAS > 5%, and an LAS/LAVi ratio >0.25%/mL/m2 compared with lower cut-off values [log-rank: heart rate (HR) 3.5, 95% confidence interval (CI) 1.8-7.3, P = 0.004; log-rank: HR 3.6, 95% CI 2-7.9, P < 0.01; log-rank: HR 3.27, 95% CI 1.4-7.7, P = 0.007]. CONCLUSION: In AHF of any LVEF, LA dynamics is highly predictive of re-hospitalization and cardiovascular outcome and allows to ease risk-stratification, potentially becoming an early reference target for improving long-term outcome.

Phenotyping congestion in acute heart failure by renal flow and right heart to pulmonary circulation coupling.

AIMS: In acute heart failure (AHF), kidney congestion is basic to treatment and prognosis. Its aetiology is manifold and quite unexplored in details mainly regarding the right heart to pulmonary circulation (Pc) coupling. We investigated the right heart to kidney interrelationship by Doppler renal flow pattern, right atrial dynamics, and right ventricular (RV) function to Pc coupling in AHF. METHODS AND RESULTS: In 119 AHF patients, echocardiographic and renal Doppler data were analysed. Univariate and multivariate regression models were performed to define the determinants of a quantitative parameter of renal congestion, the renal venous stasis index (RVSI). When grouped according to different intra-renal venous flow patterns, no differences were observed in haemodynamics and baseline renal function. Nonetheless, patients with renal Doppler evidence of congestion showed a reduced RV function [tricuspid annular plane systolic excursion (TAPSE), S'-wave velocity, and fractional area change], impaired RV to Pc coupling [TAPSE/pulmonary artery systolic pressure (PASP) ratio], and right atrial peak longitudinal strain (RAPLS), along with signs of volume overload [increased inferior vena cava (IVC) diameters and estimated right atrial pressure]. Univariate and multivariate regression analyses confirmed TAPSE/PASP, RAPLS, and IVC diameter as independent determinants of the RVSI. RVSI was the only variable predicting the composite outcome (cardiac death, heart failure hospitalization, and haemodialysis). An easy-to-use echo-derived right heart score of four variables provided good accuracy in identifying kidney congestion. CONCLUSIONS: In AHF, the renal venous flow pattern combined with a right heart study phenotypes congestion and clinical evolution. Keys to renal flow disruption are an impaired right atrial dynamics and RV-Pc uncoupling. Integration of four right heart echocardiographic variables may be an effective tool for scoring the renal congestive phenotype in AHF.

Prognostic value of cardiopulmonary exercise testing in a European cohort with cardiovascular risk factors absent of a cardiovascular disease diagnosis.

INTRODUCTION: Cardiorespiratory fitness (CRF) is now considered a vital sign. Cardiopulmonary exercise testing (CPET) is the gold-standard assessment of CRF; peak oxygen consumption (VO2) and the minute ventilation/carbon dioxide production (VE/VCO2) slope are considered primary CPET measures of CRF. More work is needed to determine the role of this exercise assessment in the primary care setting. METHODS: 695 subjects (mean age: 62 ± 13 years, body mass index: 28.9 ± 5.3 kg/m2, 375 female and 320 male) underwent CPET using a cycle ergometer. 95% of the cohort had one or more major cardiovascular risk factor (i.e., obesity, smoking, dyslipidemia, hypertension, diabetes); no subject was diagnosed with cardiovascular disease (CVD) at the time of CPET. Subjects were tracked for the composite endpoint of cardiovascular mortality or hospital admission. RESULTS: Mean peak VO2, VE/VCO2 slope and peak respiratory exchange ratio were 17.8 ± 5.8 mlO2•kg-1•min-1, 26.7 ± 4.1, and 1.18 ± 0.13, respectively. There were 42 composite events during the 64 ± 18 month tracking period. Both peak VO2 (Chi-square 16.3, p < 0.001) and the VE/VCO2 slope (Chi-square 14.9, p < 0.001) were significant univariate predictors of the composite endpoint. The VE/VCO2 slope added significant predictive value to peak VO2 and was retained in the multivariate regression (residual Chi-square 7.0, p = 0.008). DISCUSSION: These results support the prognostic value of CPET prior to a CVD diagnosis. The prognostic value of the VE/VCO2 slope, not commonly the focus of CPET trials in patients with one or more major cardiovascular risk factors but without a confirmed CVD diagnosis, is a particularly novel finding in the current study.

Revisiting and Implementing the Weber and Ventilatory Functional Classifications in Heart Failure by Cardiopulmonary Imaging Phenotyping.

Background In heart failure, the exercise gas exchange Weber (A to D) and ventilatory classifications (VC-1 to VC-4) historically define disease severity and prognosis. However, their applications in the modern heart failure population of any left ventricular ejection fraction combined with hemodynamics are undefined. We aimed at revisiting and implementing these classifications by cardiopulmonary exercise testing imaging. Methods and Results 269 patients with heart failure with reduced (n=105), mid-range (n=88) and preserved (n=76) ejection fraction underwent cardiopulmonary exercise testing imaging, primarily assessing the cardiac output (CO), mitral regurgitation, and mean pulmonary arterial pressure (mPAP)/CO slope. Within both classes, a progressively lower exercise CO, higher mPAP/CO slopes, and mitral regurgitation (P<0.01 all) were observed. After adjustment for age and sex, Cox proportional hazard regression analyses showed that Weber (hazard ratio [HR], 2.9; 95% CI, 1.8-4.7; P<0.001) and ventilatory classes (HR, 1.4; 95% CI, 1.1-2.0; P=0.017) were independently associated with outcome. The best stratification was observed when combining Weber (A/B or C/D) with severe ventilation inefficiency (VC-4) (HR, 2.7; 95% CI, 1.6-4.8; P<0.001). At multivariable analysis the best hemodynamic determinants of peak oxygen consumption and ventilation to carbon dioxide production slope were CO (ß-coefficient, 0.72±0.16; P<0.001) and mPAP/CO slope (ß-coefficient, 0.72±0.16; P<0.001), respectively. Conclusions In the contemporary heart failure population, the Weber and ventilatory classifications maintain their prognostic ability, especially when combined. Exercise CO and mPAP/CO slope are the best predictors of peak oxygen consumption and ventilation to carbon dioxide production slope classifications representing the main targets of interventions to impact functional class and, likely, event rate.

Exercise-induced mitral regurgitation and right ventricle to pulmonary circulation uncoupling across the heart failure phenotypes.

Exercise-induced mitral regurgitation (Ex-MR) is one of the mechanisms that contribute to reduced functional capacity in heart failure (HF). Its prevalence is not well defined across different HF subtypes. The aim of the present study was to describe functional phenotypes and cardiac response to exercise in HFrEF, HFmrEF, and HFpEF, according to Ex-MR prevalence. A total of 218 patients with HF [146 men, 68 (59-78) yr], 137 HFrEF, 41 HFmrEF, 40 HFpEF, and 23 controls were tested with cardiopulmonary exercise test combined with exercise echocardiography. Ex-MR was defined as development of at least moderate (≥2+/4+) regurgitation during exercise. Ex-MR was highly prevalent in the overall population (52%) although differed in the subgroups as follows: 82/137 (60%) in HFrEF, 17/41 (41%) in HFmrEF, and 14/40 (35%) in HFpEF (P < 0.05). Ex-MR was associated with a high rate of ventilation (VE) to carbon dioxide production (VCO2) in all HF subtypes [31.2 (26.6-35.6) vs. 33.4 (29.6-40.5), P = 0.004; 28.1 (24.5-31.9) vs. 34.4 (28.2-36.7), P = 0.01; 28.8 (26.6-32.4) vs. 32.2 (29.2-36.7), P = 0.01] and with lower peak VO2 in HFrEF and HFmrEF. Exercise right ventricle to pulmonary circulation (RV-PC) uncoupling was observed in HFrEF and HFpEF patients with Ex-MR [peak TAPSE/SPAP: HFrEF 0.40 (0.30-0.57) vs. 0.29 (0.23-0.39), P = 0.006; HFpEF 0.44 (0.28-0.62) vs. 0.31 (0.27-0.33), P = 0.05]. HFpEF with Ex-MR showed a distinct phenotype characterized by better chronotropic reserve and peripheral O2 extraction.NEW & NOTEWORTHY Ex-MR is a common mechanism across the spectrum of HF subtypes and combines with ventilatory inefficiency and RV-PC uncoupling. Interestingly, in HFpEF, Ex-MR emerged as unexpectedly prevalent and peculiarly associated with increased chronotropic response and peripheral O2 extraction as potential adaptive mechanisms to backward flow redistribution.

Central role of left atrial dynamics in limiting exercise cardiac output increase and oxygen uptake in heart failure: insights by cardiopulmonary imaging.

AIMS: In heart failure (HF), the haemodynamic response to exercise in relation to left atrial (LA) dynamics is unexplored. We sought to define whether abnormal LA dynamics during exercise may play a role in cardiac output (CO) limitation and tested its ability to predict outcome. METHODS AND RESULTS: A total of 195 HF patients with reduced (n = 105), mid-range (n = 48), and preserved (n = 42) left ventricular ejection fraction (LVEF) and 46 non-cardiac dyspnoea (NCD) subjects underwent cardiopulmonary imaging with assessment of LA strain and strain rate (sra). HF patients, irrespective of LVEF, exhibited a significantly impaired LA strain and LA sra at rest, during exercise and recovery compared to NCD subjects with a blunted response in CO and right ventricular to pulmonary circulation coupling. LA strain and LA sra during exertion were significantly correlated with peak stroke volume index, peak CO and peak cardiac power output (R = 0.33, 0.48, 0.50 and R = 0.36, 0.51, 0.52 for LA strain and LA sra, respectively; all P < 0.001). In HF, after adjustment for age, gender, left atrial volume index, peak mitral regurgitation > 2, peak LVEF and peak heart rate, a higher LA strain (1% increase) during exercise was associated with a higher peak stroke volume index (mL/m2 ), CO (L/min) and cardiac power output (mmHg L/min) at multivariable analyses (ß-coefficients ± standard error = 0.23 ± 0.07, 0.046 ± 0.014 and 0.012 ± 0.004, respectively; P < 0.05). The same associations were found also for LA sra (absolute value) (1/s increase, ß-coefficients ± standard error = 1.91 ± 0.68, 0.43 ± 0.14 and 0.12 ± 0.04, respectively; P < 0.05). Exercise LA strain (adjusted hazard ratio 0.94, 95% confidence interval 0.92-0.97, P < 0.001) and LA sra (adjusted hazard ratio 0.60, 95% confidence interval 0.43-0.84, P = 0.003) were associated with a worse outcome after adjusting for age and gender. CONCLUSIONS: In HF, LA dynamics may play a key role in exercise CO increase due to an impaired forward (left ventricular filling) and backward (right ventricular to pulmonary circulation uncoupling) combination of mechanisms, irrespective of LVEF. The blunted LA strain and LA sra reserve during exercise are associated with a worse cardiopulmonary performance and outcome.

Redistribution of cardiac output during exercise by functional mitral regurgitation in heart failure: compensatory O2 peripheral uptake to delivery failure.

Functional mitral regurgitation (MR) is prognostic in heart failure (HF). MR favors an nonphysiological exercise central cardiac output (CO) redistribution which adds to oxygen (O2) delivery failure. The consequences of this redistribution in O2 supply have not been explored previously. We aimed at evaluating the putative role of cardiac output (CO) and O2 arteriovenous [C(a-v)O2] difference in the attained peak V̇o2 in advanced HF with reduced ejection fraction (HFrEF) and MR. 134 HFrEF patients and 80 controls with no HF underwent exercise gas exchange combined with CO and C(a-v)O2 estimated by echo-Doppler technique. The HF population was divided into two groups: HF with severe rest MR (MR+ group; n = 36) and no to mild MR (MR- group; n = 98). HF groups did not differ in rest CO (MR+ vs. MR- 3.4 ± 1.8 vs. 3.8 ± 1.0 L/min; P = 0.32) and showed a trend for a higher C(a-v)O2 at rest (9.0 ± 4.0 vs. 8.0 ± 2.0 mL O2/100 mL; P = 0.14). In HF, CO and C(a-v)O2 at rest were significantly lower and higher compared with controls. At peak exercise, MR+ compared with MR- exhibited a significant reduction in peak V̇o2 11.6 ± 3.0 vs. 13.7 ± 3.6 ml O2·kg-1·min-1; P < 0.01) with a lower O2 delivery (CO: 5.2 ± 3.3 vs. 7.0 ± 2.0 L/min; P < 0.01), which was partially compensated by a significantly greater O2 extraction [C(a-v)O2, 18 ± 5 vs. 15 ± 4 mL O2/100 mL; P < 0.01]. In HFrEF, severe MR is associated with impaired O2 delivery due to CO redistribution to the pulmonary circulation. C(a-v)O2 is maximalized to compensate for the reduced O2 delivery. This novel information is relevant to phenotyping and targeting mediators of functional response in HF. Specifically, findings provide directions in the understanding at which extent mitral valve repair would restore an efficient cardiac reserve by enhancing O2 delivery during exercise, likely contributing to symptom relief and hopefully impacting the clinical trajectory of HF syndrome with secondary MR.NEW & NOTEWORTHY This is an analysis involving 134 heart failure patients with reduced ejection fraction versus 80 controls investigated during functional evaluation with gas exchange and hemodynamic, addressing the severe MR phenotype and testing the hypothesis that the backward cardiac output redistribution to the lung during exercise impairs delivery and overexpresses peripheral extraction. This information is new and has important implications in the management of heart failure.

Exercise chronotropic incompetence phenotypes the level of cardiovascular risk and exercise gas exchange impairment in the general population. An analysis of the Euro-EX prevention trial.

BACKGROUND: Chronotropic insufficiency (CI) is defined as the inability of the heart to increase its rate commensurate with increased demand. Exercise CI is an established predictor of major adverse cardiovascular events in patients with cardiovascular diseases. AIM: The aim of this study was to evaluate how exercise CI phenotypes different levels of cardiovascular risk and how it may better perform in defining cardiovascular risk when analysed in the context of cardiopulmonary exercise test (CPET)-derived measures and standard echocardiography in a healthy population with variable cardiovascular risk profile. METHODS: Apparently healthy individuals (N = 702, 53.8% females) with at least one major cardiovascular risk factor (MCVRF; hypertension, diabetes, tabagism, dyslipidaemia, body mass index > 25), enrolled in the Euro-EX prevention trial, underwent CPET. CI was defined as the inability to reach 80% of the chronotropic index, that is, the ratio of peak heart rate - rest heart rate/peak heart rate - age predicted maximal heart rate (AMPHR: 220 - age), they were divided into four groups according to the heart rate reserve (<80%>) and respiratory gas exchange ratio (RER; < 1.05>) as a marker of achieved maximal performance. Subjects with a RER < 1.05 (n = 103) were excluded and the final population (n = 599) was divided into CI group (n = 472) and no-CI group (n = 177). RESULTS: Compared with no-CI, CI subjects were more frequently females with a history of hypertension in a high rate. CI subjects also exhibited a significantly lower peak oxygen uptake (VO2) and circulatory power and an echocardiographic pattern indicative of higher left atrial volume index and left ventricular mass index. An inverse stepwise relationship between heart rate reserve and number of MCVRFs was observed (one MCVRF: 0.71 ± 0.23; two MCVRFs: 0.68 ± 0.24, three MCVRFs: 0.64 ± 0.20; four MCVRFs: 0.64 ± 0.23; five MCVRFs: 0.57 ± 18; p < 0.01). In multivariate analysis the only variable found predicting CI was peak VO2 (p < 0.05; odds ratio 0.91; confidence interval 0.85-0.97). CONCLUSIONS: In a population of apparently healthy subjects, exercise CI is common and phenotypes the progressive level of cardiovascular risk by a tight relationship with MCVRFs. CI patients exhibit some peculiar abnormal exercise gas exchange patterns (lower peak VO2 and exercise oscillatory ventilation) and echo-derived measures (higher left atrium size and left ventricle mass) that may well anticipate evolution toward heart failure.

Left Atrial Dynamics During Exercise in Mitral Regurgitation of Primary and Secondary Origin: Pathophysiological Insights by Exercise Echocardiography Combined With Gas Exchange Analysis.

OBJECTIVES: The aim of this study was to identify the pattern of exercise left atrial (LA) dynamics, its gas exchange correlates, and prognosis in mitral regurgitation (MR) of primary and secondary origin. BACKGROUND: The adaptive response and clinical significance of LA function during exercise in MR is undefined. METHODS: A total of 196 patients with MR (81 with primary MR, 115 with secondary MR) and 54 control subjects underwent exercise stress echocardiography and cardiopulmonary exercise testing with LA function assessment. Patients with MR were divided into 4 groups according to etiology and severity using a cutoff of 3+. RESULTS: LA dynamics was studied using speckle-tracking echocardiography. Compared with control subjects, patients with MR had a lower LA strain and strain rate at rest. Exercise LA strain and LA strain rate progressively worsened from primary MR <3+ through secondary MR ≥3+. In primary MR, some reserve in exercise LA strain and LA strain rate was observed, but not in secondary MR. In secondary MR, LA strain at rest and during exercise (18.1 ± 5.7 s-1, 18.3 ± 6.9 s-1, 18.6 ± 5.5 s-1, 13.9 ± 3.8 s-1) and peak oxygen consumption (11.7 ± 3 ml/min/kg) were decreased compared with the other groups. In secondary MR ≥3+, the slope of ventilation versus carbon dioxide was higher compared with the other groups: 35.1 (interquartile range [IQR]: 29.0 to 44.2) compared with control subjects: 26.5 (IQR: 24.4 to 29.0); patients with primary MR <3+ (26.9; IQR: 24.0 to 31.9); those with primary MR >3+ (25.5; IQR: 23.4 to 29.0); and those with secondary MR <3+ (29.5; IQR: 26.5 to 33.7) (p < 0.05 for all). A progressive impairment in exercise LA mechanics combined with limited cardiac output increase and right ventricular-to-pulmonary circulation uncoupling was observed from primary to secondary MR. LAS during exercise was predictive of all-cause mortality and hospitalization for heart failure. CONCLUSIONS: In MR of any origin, exercise LA reservoir and pump function are impaired. For similar MR extent, secondary MR exhibits worse atrial function, resulting in the lowest exercise performance, limited cardiac output increase, impaired right ventricular-to-pulmonary circulation coupling, and the highest event rate.

Left Atrial Function Dynamics During Exercise in Heart Failure: Pathophysiological Implications on the Right Heart and Exercise Ventilation Inefficiency.

OBJECTIVES: The hypothesis of this study was that left atrial (LA) dynamic impairment during exercise may trigger right ventricular (RV)-to-pulmonary circulation (PC) uncoupling and ventilation inefficiency. BACKGROUND: LA function plays a key role in the hemodynamics of heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Extensive investigation of LA dynamics, however, has been performed exclusively at rest. METHODS: A total of 49 patients with HFrEF, 20 patients with HFpEF, and 32 healthy subjects with normal LA size and reservoir function (LA volume index <34 ml/m2 and peak left atrial strain [LA-strain] during LA relaxation >23%) were prospectively enrolled. They underwent cardiopulmonary exercise testing and contemporary echo-Doppler assessment of LA-strain and LA-strain rate and of RV-to-PC coupling (pulmonary arterial systolic pressure/tricuspid annular peak systolic excursion ratio), measured at rest, at 40% of predicted peak oxygen consumption, and during recovery. RESULTS: In control subjects, LA-strain increased during exercise and recovery. Patients with HFpEF exhibited some LA-strain increase during exercise and recovery, whereas no changes occurred in those with HFrEF. The baseline LA-strain rate was greater in control subjects; a significant enhancement during recovery was observed only in this group. In both the HFpEF and HFrEF cohorts, RV-to-PC uncoupling and LA-strain at rest, exercise, and recovery significantly correlated with pulmonary arterial systolic pressure/tricuspid annular peak systolic excursion, as well as ventilation versus carbon dioxide slope, in a continuous fashion across groups (r = -0.63 and r = -0.59, r = -0.65 and r = -0.50, and r = -0.70 and r = -0.53 for control subjects, HFpEF, and HFrEF, respectively; p < 0.05). CONCLUSIONS: In heart failure, an impaired LA-strain response is a key hemodynamic trigger for RV-to-PC uncoupling and exercise ventilation inefficiency with some overlap between HFpEF and HFrEF phenotypes. Reversibility of LA dynamics seems to be an unmet target of specific therapeutic interventions.

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.

Right Ventricular Contractile Reserve and Pulmonary Circulation Uncoupling During Exercise Challenge in Heart Failure: Pathophysiology and Clinical Phenotypes.

OBJECTIVES: Right ventricular (RV) exercise contractile reserve (RVECR), its phenotypes, and its functional correlates are among the unresolved issues with regard to the role of the right ventricle in heart failure (HF) syndrome, and understanding these issues constitutes the objective of this study. BACKGROUND: Although the role of the right ventricle in HF syndrome might be fundamental, the pathophysiology of the failing right ventricle has not been extensively investigated. METHODS: Ninety-seven patients with HF (mean age 64 years, 70% men, mean left ventricular ejection fraction 33 ± 10%) underwent maximal exercise stress echocardiographic and cardiopulmonary exercise testing. RVECR and RV-to-pulmonary circulation (PC) coupling were assessed using the length-force relationship (tricuspid annular plane systolic excursion [TAPSE] vs. pulmonary artery systolic pressure) and the slope of mean pulmonary artery pressure versus cardiac output. On the basis of TAPSE, patients were categorized into 3 groups: those with TAPSE at rest ≥16 mm (group A, n = 60) and those with TAPSE at rest <16 mm, who were divided according to median TAPSE at peak exercise (15.5 mm) into 2 subgroups (group B, ≥15.5 mm, n = 19; group C, <15.5 mm, n = 18). RESULTS: Although they had similar left ventricular ejection fractions and rest RV impairment, compared with patients in group C, those in group B showed some degree of RVECR (upward shift of the length-force relationship), better RV-to-PC coupling (lower mean pulmonary artery pressure vs. cardiac output slope), and greater ventilatory efficiency (lower slope of minute ventilation to carbon dioxide output). Rest mitral regurgitation and net changes in pulmonary artery systolic pressure were the variables retained in the best regression model as correlates of RVECR. CONCLUSIONS: In patients with HF, RVECR unmasks different phenotypes. Impaired RV function at rest might not invariably lead to unfavorable RVECR and exercise RV-to-PC coupling. Testing these variables appears useful even in more advanced stages of HF to define various clinical conditions and, most likely, to define different levels of risk.

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.

Role of right ventricle and dynamic pulmonary hypertension on determining ΔVO2/ΔWork Rate flattening: insights from cardiopulmonary exercise test combined with exercise echocardiography.

BACKGROUND: Several cardiovascular diseases are characterized by an impaired O2 kinetic during exercise. The lack of a linear increase of Δoxygen consumption (VO2)/ΔWork Rate (WR) relationship, as assessed by expired gas analysis, is considered an indicator of abnormal cardiovascular efficiency. We aimed at describing the frequency of ΔVO2/ΔWR flattening in a symptomatic population of cardiac patients, characterizing its functional profile, and testing the hypothesis that dynamic pulmonary hypertension and right ventricular contractile reserve play a major role as cardiac determinants. METHODS AND RESULTS: We studied 136 patients, with different cardiovascular diseases, referred for exertional dyspnoea. Cardiopulmonary exercise test combined with simultaneous exercise echocardiography was performed using a symptom-limited protocol. ΔVO2/ΔWR flattening was observed in 36 patients (group A, 26.5% of population) and was associated with a globally worse functional profile (reduced peak VO2, anaerobic threshold, O2 pulse, impaired VE/VCO2). At univariate analysis, exercise ejection fraction, exercise mitral regurgitation, rest and exercise tricuspid annular plane systolic excursion, exercise systolic pulmonary artery pressure, and exercise cardiac output were all significantly (P<0.05) impaired in group A. The multivariate analysis identified exercise systolic pulmonary artery pressure (odds ratio, 1.06; confidence interval, 1.01-1.11; P=0.01) and exercise tricuspid annular plane systolic excursion (odds ratio, 0.88; confidence interval, 0.80-0.97; P=0.01) as main cardiac determinants of ΔVO2/ΔWR flattening; female sex was strongly associated (odds ratio, 6.10; confidence interval, 2.11-17.7; P<0.01). CONCLUSIONS: In patients symptomatic for dyspnea, the occurrence of ΔVO2/ΔWR flattening reflects a significantly impaired functional phenotype whose main cardiac determinants are the excessive systolic pulmonary artery pressure increase and the reduced peak right ventricular longitudinal systolic function.