Abnormal Hemodynamic Response Research Articles

TAPSE/sPAP at peak exercise as a surrogate of RV-PA uncoupling can predict exercise-induced pulmonary hypertension in symptomatic patients with chronic thromboembolic pulmonary disease

Abstract Background and aim Chronic thromboembolic disease (CTED) refers to the presence of chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but with exercise limitation caused by established vasculopathy. Symptoms after an acute pulmonary embolism (PE) with persistent lung perfusion defects need a complete diagnostic approach. Exercise echocardiography (ex-echo), with surrogate parameters of ventricular-arterial (VA) coupling could be of interest to non-invasively assess a pathological hemodynamic response. The aim of this study is to analyze the role of ex-echo and non-invasive assessment of VA coupling by echocardiography in predicting an abnormal hemodynamic response in symptomatic patients with chronic thrombotic pulmonary vascular occlusion. Methods Symptomatic patients with confirmed perfusion defects in lung V/Q scintigraphy despite optimal anticoagulant therapy for at least 3 months after an acute PE were selected. Relevant PH at rest was ruled-out (mPAP <25 mmHg, PVR <3 Wu, PAWP <15 mmHg, according to available definition at the time). Right heart catheterization with incremental exercise protocol (adapted cycle ergometer), with simultaneous transthoracic echo were performed. Parameters were collected at each exercise level. A mPAP/CO slope >3 mmHg·L−1·min−1 measured invasively was considered an abnormal hemodynamic response to exercise. Right VA coupling was estimated as TAPSE/sPAP ratio. A non invasive echo mPAP/CO slope was obtained from Doppler measurements. Results 31 patients (32% women, mean age 51.8 ± 14.7 y.) were included. Fourteen patients (45%) developed ex-PH. Baseline and peak exercise characteristics and parameters according to hemodynamic response are shown in Table 1. Moderate significative correlations between invasive hemodynamics and echo derived parameters at peak exercise were observed: sPAP: r=0.793 (p <0.001), CO r=0.532 (p 0.003), mPAP/CO slope r=0.458 (p 0.012). Peak exercise TAPSE/sPAP showed an AUC=0.85 (CI95% 0.70-1.00, fig. 1), and a cutoff point of <0.52 mm/mmHg, showed a S 80% / E 93% PPV 92% and NPV 81%, to predict an abnormal response. The echo derived mPAP/CO slope showed an AUC=0.78 (CI95% 0.59-0.96), and a cutoff point of > 2.44 mmHg·L−1·min−1 showed a S and E of 85% and 67% PPV 71 % and NPV of 83% to predict ex-PH. Abnormal septal motion at peak exercise showed a S 90%, E 78%, PPV 71% and NPV of 93% to predict ex-PH. Conclusions In our study cohort, up to 45% of symptomatic patients with persistent pulmonary thrombosis after a PE, without relevant PH at rest, developed ex-PH. New echo-derived parameters such as TAPSE/sPAP, a surrogate RV-PA coupling parameter, and echo-mPAP/CO slope, showed a good performance to predict an abnormal hemodynamic response. Ex-echo, feasible, non invasive and widely available, might represent a useful tool for the selection of patients for invasive hemodynamic workup.Peak exercise TAPSE/sPAP ROC curveTable 1

Usefulness of cardiopulmonary exercise test to detect exercise pulmonary hypertension in the post pulmonary embolim follow-up

Abstract Functional impairment is largely reported after symptomatic pulmonary embolism (PE). Chronic thromboembolic pulmonary disease (CTED) refers to the presence of chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but with incipient vasculopathy responsible for exercise limitation. Exercise haemodynamic studies have emerged to detect an abnormal response suggesting an established vasculopathy or an abnormal left ventricular filling pressure. We hypothesized that exercise intolerance due to an abnormal haemodynamic response during exercise might be unmasked by the parameters exhibited at the cardiopulmonary exercise test (CPET) in diagnostic workup after PE in symptomatic patients. Our aim was to correlate the values reached in the CPET pattern with haemodynamic response during exercise right heart catheterization (RHC) in patients with CTED suspicion. Methods We selected symptomatic patients with confirmed perfusion defects in lung scintigraphy despite optimal anticoagulant therapy for a minimum of 3 months after a PE with normal lung function tests. Left heart disease and significant PH were ruled out with RHC (inclusion criteria implied mean pulmonary arterial pressure (mPAP) < 25 mmHg and pulmonary vascular resistance (PVR) < 3 WU and pulmonary arterial wedge pressure (PAWP) ≤15 mmHg). Exercise RHC was performed sequentially 24 hours after CPET. The exercise protocol was the same for both tests. Pulmonary pressure and cardiac output (CO) were collected at each exercise leel. Exercise PH (ex-PH) was considered when mPAP/CO slope >3 mmHg·L−1·min−1. We made a subanalysis according to the new PH criteria (mPAP >20mmHg & PVR > 2 WU at rest). Results 39 patients (median age 52.7 ± 15.7 years, 36% females) were included. 21 (53.8%) showed abnormal haemodynamic behaviour, 6(15.4%) of them due to abnormal PWAP/CO slope. Baseline characteristics are summarized in Table 1. Patients with abnormal exercise response showed worse ventilatory efficiency at exercise: 1) reduced partial end-tidal of carbon dioxide (PetCO2) at the anaerobic threshold (AT) (32.0 Vs 36.4, p=0.001), 2) a steeper VE/CO2 slope (35.6 Vs 30.9, p=0.009) and 3) a higher ventilatory equivalent for CO2 at the AT (35.5 Vs 31.6, p=0.004) compared to the group with normal hemodynamic behaviour. Oxygen consumption at the AT and peak oxygen consumption were slightly decreased without statistically significant differences between groups.Of the global cohort, 11 patients reached new resting PH criteria, and 92% of them showed ex-PH. Ventilatory efficiency showed differences in the subgroup with normal resting hemodynamic values, especially lower PetCO2 at the AT (31.8 Vs 35.0, p=0.008) (Figure 2). Conclusion In the context of persistent dyspnoea after PE, ventilatory inefficiency is a sign of exercise pulmonary hypertension, and CPET could identify patients with abnormal exercise response despite normal hemodynamic values at rest.

Resting RV-PA uncoupling as predictor of exercise induced pulmonary hypertension in patients with chronic thromboembolic pulmonary disease

Abstract Background and aim Chronic thromboembolic disease (CTED) refers to the presence of chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but with exercise limitation caused by established vasculopathy. Symptoms after an acute pulmonary embolism (PE) with persistent lung perfusion defects need a complete diagnostic approach. Screening these symptomatic patients with resting echocardiography (echo) is challenging. The aim of this study is to analyze the echocardiographic predictors at rest of exercise induced PH (ex-PH) in patients with suspected CTED. Methods Symptomatic patients with confirmed perfusion defects in lung V/Q scintigraphy despite optimal anticoagulant therapy for at least 3 months after an acute PE were selected. Structural heart disease or pulmonary disease were excluded. Relevant PH at rest was ruled-out (mPAP <25 mmHg, PVR <3 Wu, PAWP <15 mmHg according to available definition at the time). A right heart catheterization with incremental exercise protocol (cycle ergometer), and simultaneous transthoracic echo were performed. Hemodynamic and echo parameters were collected at each exercise level. A mPAP/CO slope >3 mmHg·L−1·min−1 was considered an abnormal hemodynamic response to exercise. Right V-PA coupling was estimated as TAPSE/sPAP and RV free wall global longitudinal strain (RV-GLS)/sPSP ratios. Results 31 patients (32% women, mean age 51.8 ± 14.7 y) were included. Fourteen patients (45%) developed ex-PH. Baseline characteristics according to invasive hemodynamic response are shown in Table 1. Resting RV function (TAPSE and RV-GLS), but not size, was significatively impaired in the ex-PH cohort. Resting echo sPAP or TR max velocity did not achieve any difference between groups, although invasive sPAP did. Resting TAPSE/sPAP and RV-GLS/sPAP were significantly reduced in the ex-PH group. In ROC curve, resting TAPSE/sPAP showed an AUC 0.75 (CI 95% 0.56-0.95) to predict ex- PH. A cutoff point of <0.62 mm/mmHg at rest, showed a S 88% / E 71%, PPV 78.9 % and NPV 83.3%. Resting RV-GLS/sPAP ratio showed an AUC 0.859 (CI 95% 0.708 – 0.990) to predict ex- PH. A cutoff point of > - 0.67 %/mmHg, showed a S 75.0% / E 87.5%, PPV 78.2 % and NPV 82.4%. to predict ex- PH. Conclusions Exercise limitation appears to be attributable to ex-PH in up to 45% of symptomatic patients with persistent pulmonary thrombosis after a PE without relevant PH at rest. Echo derived parameters at rest, surrogates of RV-PA uncoupling, such as TAPSE/sPAP and RV-GLS/sPAP, could be of great interest to identify patients with abnormal hemodynamic response to exercise, and help in the initial non invasive diagnostic workup of these increasingly group of patients.ROC curvesTable 1Resting Echo values

Abstract 14279: Improved Pressure-Flow Relationship With Sacubitril/Valsartan: A 6-min Walk Stress Echocardiographic Study

Background: In the clinical setting, there are various techniques for stress echocardiography, of which the 6-minute walk (6MW) test is a straightforward and utilized one. An abnormal hemodynamic response to exercise is indicated by a ΔmPAP/ΔCO slope of greater than 3 mmHg/L/min between rest and exercise. This response is associated with impaired prognosis in patients with exercise dyspnea and several cardiovascular diseases. Hypothesis: Our hypothesis was that pressure-flow relationship of the pulmonary circulation obtained by 6MW stress echocardiography would be enhanced with treatment. Aims: The aim of this study was to assess the effects of administration of Sacubitril/Valsartan on cardiac function in heart failure. Methods: We prospectively enrolled 39 patients with heart failure. The 6MW test was performed indoors in a flat, straight corridor. The peak tricuspid regurgitation jet, early diastolic transmitral flow velocity and early diastolic mitral motion were obtained by echocardiography post-6MW. We calculated the slope of ΔmPAP/ΔCO as a parameter of pulmonary hypertension. Follow-up echocardiographic studies were performed after 1 year. Results: Left ventricular diameter and volume were significantly reduced (LVDd; 59.3±7.7mm vs 56.0±8.6mm, P<0.001, LVEDV; 160.7±49.6ml vs 136.0±54.3ml, P<0.001), and LVEF was significantly improved (37.6±11.3% vs 44.9±11.5%, P<0.001). Among the 31 patients who underwent 6MW stress echocardiographic study at baseline and 1 year later, 6MW distance increased after treatment (380m vs 430m, P=0.003). The ΔmPAP/ΔCO by 6MW stress decreased with treatment (6.9mmHg/L/min vs 2.8mmHg/L/min, P=0.002). Conclusions: Initiation of Sacubitril/Valsartan was associated with improvement of left ventricular size and LVEF. Additionally, the 6MW distance increased and the ΔmPAP/ΔCO was improved to within normal range with treatment. Sacubitril/Valsartan distinctly improved cardiac reactivity to exercise.

Differences in Cardiovascular Regulation to Head-up Tilt between Healthy and Hypertensive Subjects.

To date there have only been limited studies exploring abnormal hemodynamic responses to head-up tilt tests (HUTs) in elderly, treated patients with hypertension. Cardiovascular regulation in response to HUT as well as upright hemodynamics may be altered when older hypertensive patients with antihypertensive treatments are studied. Hypertensive patients with and without receiving antihypertensive medication and above the age of 45 were recruited in this study. This study compared the cardiovascular responses to HUT and at rest between healthy and hypertensives using non-invasive hemodynamic measurements. Parameters such as systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), stroke index (SI) and total peripheral resistance index (TPRI) were measured in 40 subjects (20 healthy and 20 hypertensives) for 10-min supine baseline, 10-min HUT at 70◦ and 6-min supine recovery. At rest and during HUT, SBP and TPRI were significantly higher in hypertensives together with a significantly smaller baseline SI. In response to HUT, both groups showed changes in hemodynamic parameters at differing degrees. During recovery, all parameters returned to the baseline range. Our findings indicated that hypertensive patients of older age being treated by antihypertensive drugs may have different cardiovascular changes in response to orthostatic stress.Clinical Relevance- This pilot study describes how cardiovascular regulation in response to postural change may behave differently in hypertensive elder patients taking antihypertensive drugs.

Role of cardiovascular magnetic resonance imaging and cardiopulmonary exercise test in predicting composite clinical outcomes in patients with hypertrophic cardiomyopathy.

We aimed to evaluate the additive value of cardiovascular magnetic resonance imaging (CMR) and cardiopulmonary exercise test (CPET) to predict clinical outcomes in patients with HCM. We enrolled 373 patients with HCM and normal left ventricular systolic function who underwent CPET and CMR. The primary outcome was a clinical composite of all-cause death, cardiac transplantation, stroke, heart failure requiring hospitalization and defibrillator implantation. During a follow-up of 70.70 ± 30.74 months, there were 84 composite clinical events. Peak oxygen consumption during CPET was significantly lower (18.51±13.25 vs. 24.59±13.28 mL/kg/min, p < 0.001) and abnormal hemodynamic response to exercise was more frequently detected (41.7 vs. 20.8%, p<0.001) in the group with composite clinical events. The extent of late gadolinium enhancement was larger in the event group (15.39±10.53 vs. 11.97±9.53%LV, p<0.001). Selective parameters were added stepwise to conventional clinical parameters; the final model, where CPET and CMR parameters were added, was verified to have the highest increment value for clinical outcome prediction (p<0.001). This study demonstrated that CPET and CMR findings may be important clinical tools for risk stratification in HCM. Exercise capacity was an independent predictor of composite outcomes in patients with HCM, with incremental value as a risk factor when added to the alleged parameters. These findings could help physicians monitor and manage patients with HCM in the real clinical field.

Disproportionate exercise-induced pulmonary hypertension in relation to cardiac output in heart failure with preserved ejection fraction: a non-invasive echocardiographic study.

Pulmonary hypertension (PH) and pulmonary vascular remodelling are common in patients with heart failure with preserved ejection fraction (HFpEF). Many patients with HFpEF demonstrate an abnormal pulmonary haemodynamic response to exercise that is not identifiable at rest. This can be estimated non-invasively by the mean pulmonary artery pressure-cardiac output relationship (mPAP/CO slope). We sought to characterize the pathophysiology of disproportionate exercise-induced PH in relation to CO (DEi-PH) and its prognostic impact in patients with HFpEF. A total of 345 patients (166 HFpEF and 179 controls) underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. DEi-PH was defined as the mPAP/CO slope >5.2 mmHg/L/min (median value). At rest, there were no differences in right ventricular (RV) function and severity of PH between HFpEF patients with and without DEi-PH. Compared with controls (n=179) and HFpEF without DEi-PH (n=83), HFpEF with DEi-PH (n=83) demonstrated worse exercise capacity (lower peak oxygen consumption), depressed RV systolic function, impaired RV-pulmonary artery coupling, limitation in CO augmentation, more right-sided congestion, and worse ventilatory efficiency (higher minute ventilation vs. carbon dioxide volume) during peak exercise. Kaplan-Meier analyses showed that HFpEF patients with DEi-PH had higher rates of composite outcomes of all-cause mortality or heart failure events than those without (log-rank p=0.0002). Patients with HFpEF and DEi-PH demonstrated distinct pathophysiologic features that become apparent only during exercise. These data suggest that DEi-PH is a pathophysiologic phenotype of HFpEF and reinforce the importance of exercise stress echocardiography for detailed characterization of HFpEF.

Effects of acute high-altitude exposure on working memory: A functional near-infrared spectroscopy study.

Inadequate oxygen availability may lead to impairment of neurocognitive functions. The aim of the present study was to investigate the effect of acute high-altitude exposure on the cerebral hemodynamic response and working memory. The same subjects performed working memory exercises with forward and backward digit span tasks both under normal oxygen conditions and in large simulated hypobaric hypoxia chambers, and a series of physiological parameters were evaluated. Functional near-infrared spectroscopy was used to measure cerebral blood flow changes in the dorsolateral prefrontal cortex (DLPFC) during the tasks. Compared with normoxic conditions, under hypoxic conditions, the heart rate and blood pressure increased, blood oxygen saturation decreased significantly, and the forward task had similar accuracy and response time, while the backward task had lower accuracy and longer response time. Neuroimaging analysis showed increased activation in the DLPFC during the forward task and deactivation during the backward task under hypobaric hypoxia conditions. Acute high-altitude exposure leads to physiological adaptations. The abnormal hemodynamic responses of the DLPFC to hypoxia at low pressure reveal the disruption of neurocognitive function by acute high-altitude exposure, which compromises complex cognitive functions, and provides a promising application for functional near infrared spectroscopy in the exploration of neural mechanisms in the brain during high-altitude exposure.

Different diagnostic criteria agreement for exercise pulmonary hypertension in chronic thromboembolic pulmonary disease

Abstract Background Hemodynamic changes during exercise have emerged as a diagnostic tool in patients with suspected pulmonary hypertension, considering that an abnormal response may reveal an incipient vasculopathy, particularly in chronic thromboembolic disease (CTED). Since mean arterial pressure (mPAP) is considered a flow-dependent variable, diagnosis of an abnormal pulmonary hemodynamic response has changed over time. Different methods to determine a pathological mPAP to Cardiac Output (CO) ratio have been proposed. Multipoint mPAP – CO Slope &amp;gt;3 mmHg/L/min has reached board consensus for determining an abnormal pulmonary response to exercise as this method can characterize mPAP–CO response across all exercise stages. Given the technic difficulties to obtain this parameter, other criteria have been proposed. Aim To investigate the diagnostic concordance and the reproducibility of the different abnormal pulmonary exercise hemodynamic response criteria in a cohort of patients with CTED. Methods We selected symptomatic patients with confirmed perfusion defects in lung scintigraphy despite optimal anticoagulant therapy for a minimum of 6 months after a pulmonary embolism. The thrombotic burden was assessed with computed tomography (CT). Lelf Heart Disease (LHD) and significant PH were ruled out with RHC (inclusion criteria implied resting mean pulmonary arterial pressure (mPAP) &amp;lt;25 mmHg and pulmonary vascular resistance (PVR) &amp;lt;3 uW and pulmonary arterial wedge pressure (PAWP) &amp;lt;15 mmHg). Exercise RHC was performed in supine position following an incremental stepwise protocol using a cycle ergometer. Pulmonary pressures and CO estimated by thermodilution were collected at each exercise level. Total pulmonary resistance (TPR) was calculated by dividing mPAP by CO. The abnormal hemodynamic response according to the more viable proposed criteria: 1) mPAP &amp;gt;30 mmHg and TPR &amp;gt;3uW at peak exercise, 2) ΔmPAP/ ΔCO &amp;gt;3 mmHg/L/min at rest and peak exercise; was compared to the pathological reference threshold multipoint PAPm/ CO slope &amp;gt;3 mmHg/L/min. Results 22 patients (median age of 54.5±14.8 years old) were recruited. Baseline characteristics and RHC values are summarized in Figure 1. Positive agreement was 93% (77% – 98%) in case of mPAP30peak+ TPR3peak versus mPAP/CO slope (k=0.810) and 91% (74% – 97%) in case of ΔmPAP/ΔCO versus mPAP/CO slope (k=0.801). Both criteria showed high diagnostic accuracy for an abnormal response diagnosis compared with the reference. Figure 2 summarizes their respective sensitivities and specificities. Patients misdiagnosed were those whose hemodynamic response was close to the reference cut-off values (mPAP/CO slope between 2 and 4 mmHg//L/min). Conclusion In a cohort of patients with CTED without significant PH at rest or LHD,the three methods proposed to diagnose an abnormal pulmonary exercise hemodynamic response show accurate concordance. Disagreement was higher in patients with a borderline pathological response. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Sociedad Española de Cardiologia

Ventilatory inefficiency predicts abnormal hemodynamic response to exercise in chronic thromboembolic disease

Abstract Background Chronic thromboembolic disease (CTED) refers to the presence of chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest. Nevertheless, their exercise tolerance may be decreased. We hypothesized that exercise intolerance may be explained by an abnormal haemodynamic response to exercise and that this may correlate to the functional and ventilatory parameters exhibited at the cardiopulmonary exercise test (CPET). Objective To evaluate the values reached in the CPET according to the hemodynamic response to exercise at the exercise right heart catheterization (RHC) in patients with CTED. Methods We selected symptomatic patients with confirmed perfusion defects in lung scintigraphy despite optimal anticoagulant therapy for a minimum of 6 months after a pulmonary embolism with normal lung function tests. Thrombotic burden was assessed with computed tomography (CT). Left heart disease (LHD) and PH were ruled out with RHC (inclusion criteria implied mean pulmonary arterial pressure (mPAP)&amp;lt;25 mmHg and pulmonary vascular resistance (PVR)&amp;lt;3 uW and pulmonary arterial wedge pressure (PAWP)&amp;lt;15 mmHg). All patients underwent a cardiopulmonary exercise test (CPET). Exercise RHC was performed within 24 hours after CPET. The exercise protocol was the same for both tests. Pulmonary pressures and cardiac output (CO) were collected at each exercise level. Abnormal hemodynamic exercise response was considered following the proposal of the 2020 CTED consensus (mPAP/CO slope &amp;gt;3 mmHg/L/min). Results 22 patients (median age 54.5±14.8 years, 32% females) were included, of whom 13 (59%) showed an abnormal hemodynamic response (mPAP/CO slope 4.5 vs 2.3 mmHg/L/min, Figure 1A). Baseline characteristics and time from the embolic event were similar in both groups (3.4 vs 2.5 years, p=0.815) (Table 1). Patients with abnormal exercise response showed worse ventilatory efficiency at the CPET: 1) a flattened end-tidal carbon dioxide pressure pattern (PetCO2) (Figure 1B), 2) a steeper VE/CO2 slope, and 3) a higher ventilatory equivalent for CO2 at the anaerobic threshold (EQCO2_AT); compared to the group with normal hemodynamic behavior. Oxygen consumption at the anaerobic threshold (VO2_AT) and peak oxygen consumption (VO2) were slightly decreased without statistically significant differences between groups. VE/CO2 slope, EqCO2_AT and PETCO2_AT showed a moderate mPAP/CO slope correlation (r=0.66, p&amp;lt;0.001; r=0.63, p=0.003; r=−0.51, p=0.017 respectively). PetCO2_AT and EqCO2_AT accurately discriminated between both groups with an area under the receiver operating characteristic curve of 0.752 and 0.710 respectively. Conclusion In patients with CTED and normal/near normal pulmonary pressures at rest, ventilatory inefficiency parameters in CPET correlate with an abnormal hemodynamic exercise response. PETCO2 pattern and EqCO2_AT accurately discriminated the subgroup with abnormal hemodynamic behaviour. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Sociedad Española de Cardiologia

Hemodynamic pulmonary response to exercise according to different resting pulmonary hypertension thresholds in chronic thromboembolic pulmonary disease

Abstract Background Chronic thromboembolic pulmonary disease (CTEPD) defines all symptomatic patients who present mismatched perfusion defects on ventilation/perfusion (V/Q) scan and specific signs of organized fibrotic clots on computed tomography after at least three months of adequate anticoagulation in the absence of pulmonary hypertension (PH) at rest. Exercise limitation in CTED has been attributed either to an abnormal hemodynamic response to exercise or increased dead space ventilation. The proposal to decrease the PH threshold to mean pulmonary arterial pressure (mPAP) ≥20 mmHg and pulmonary vascular resistance (PVR) &amp;gt;3 uWood (uW) in all PH groups could identify a subgroup of patients with borderline PH criteria, and an abnormal response at exercise in CTEPD. Aim We sought to determine the hemodynamic behaviour at exercise according to different resting pulmonary pressures in a cohort of patients with CTEPD. Methods We selected symptomatic patients with confirmed perfusion defects in lung scintigraphy despite optimal anticoagulant therapy for a minimum of 6 months after a pulmonary embolism.Significant PH were ruled out with right heart catheterization (RHC): inclusion criteria implied mPAP &amp;lt;25 mmHg and PVR &amp;lt;3 uW and pulmonary arterial wedge pressure (PWAP) &amp;lt;15 mmHg. Exercise RHC was performed in supine following an incremental stepwise protocol using a cycle ergometer. Pulmonary pressures and cardiac output (CO) estimated by thermodilution were collected in each exercise level. Abnormal hemodynamic exercise response was defined when a value of multipoint mPAP/CO slope &amp;gt;3 mmHg L–1 min–1 was reached. Patients were stratified in three groups according to resting mPAP and PVR: 1) Normal-no PH (mPAP &amp;lt;20 mmH + RVP &amp;lt;2 uW), 2) Borderline (mPAP ≥20 + RVP &amp;lt;3 uW), 3) mild PH (mPAP ≥20 mmHg + RVP &amp;gt;3 uW). Results Twenty-two CTEPD patients were stratified into three groups 1) mild PH: 3 patients, 2) borderline PH: 11 patients and 3) no PH: 8 patients. Median age between groups did not reveal differences. At rest, the mild PH group showed higher mPAP, higher total pulmonary resistance (TPR) and lower compliance, relative to borderline and normal groups without significant differences in PWAP and stroke volume (Figure 1). At peak exercise, no differences in the estimated flow between the three groups were found, despite a substantial increase of mPAP with respect to resting pressures (57.3±11 mmHg Vs 47.7±10.0 mmHg vs 34.1±5.7 mmHg, p trend = 0.006). The prevalence of an abnormal hemodynamic response the mild, borderline and normal groups was 100%, 63.6% and 37.5% respectively. Figure 2 summarizes exercise RHC parameters. Conclusion In patients with CTEPD, the presence of borderline or mild PH at rest, predicts an abnormal hemodynamic response to exercise, when compared with patients with no PH at rest. Nevertheless, in this latter group, more than a third of patients showed an abnormal response, suggesting the presence of established pulmonary vasculopathy Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Sociedad Española de Cardiologia

Diagnostic, prognostic and differential-diagnostic relevance of pulmonary haemodynamic parameters during exercise: a systematic review.

BackgroundThe cardiopulmonary haemodynamic profile observed during exercise may identify patients with early-stage pulmonary vascular and primary cardiac diseases, and is used clinically to inform prognosis. However, a standardised approach to interpreting haemodynamic parameters is lacking.MethodsWe performed a systematic literature search according to PRISMA guidelines to identify parameters that may be diagnostic for an abnormal haemodynamic response to exercise and offer optimal prognostic and differential-diagnostic value. We performed random-effects meta-analyses of the normal values and report effect sizes as weighted mean±sd. Results of diagnostic and prognostic studies are reported descriptively.ResultsWe identified 45 eligible studies with a total of 5598 subjects. The mean pulmonary arterial pressure (mPAP)/cardiac output (CO) slope, pulmonary arterial wedge pressure (PAWP)/CO slope and peak cardiac index (or CO) provided the most consistent prognostic haemodynamic parameters during exercise. The best cut-offs for survival and cardiovascular events were a mPAP/CO slope >3 Wood units (WU) and PAWP/CO slope >2 WU. A PAWP/CO slope cut-off >2 WU best differentiated pre- from post-capillary causes of PAP elevation during exercise. Upper limits of normal (defined as mean+2sd) for the mPAP/CO and PAWP/CO slopes were strongly age-dependent and ranged in 30–70-year-old healthy subjects from 1.6 to 3.3 WU and 0.6 to 1.8 WU, respectively.ConclusionAn increased mPAP/CO slope during exercise is associated with impaired survival and an independent, prognostically relevant cut-off >3 WU has been validated. A PAWP/CO slope >2 WU may be suitable for the differentiation between pre- and post-capillary causes of PAP increase during exercise.

Predictive Value of Abnormal Hemodynamic Response to Dobutamine Stress Echocardiography in Liver Transplant Recipients

Predictive Value of Abnormal Hemodynamic Response to Dobutamine Stress Echocardiography in Liver Transplant Recipients

Elevated Left and Right Atrial Pressures Long-Term After Atrial Septal Defect Correction: An Invasive Exercise Hemodynamic Study.

BackgroundDespite correction of the atrial septal defect (ASD), patients experience atrial fibrillation frequently and have increased morbidity and mortality. We examined physical capacity, cardiac performance, and invasive hemodynamics in patients with corrected ASD.Methods and ResultsThirty‐eight corrected patients with isolated secundum ASD and 19 age‐matched healthy controls underwent right heart catheterization at rest and during exercise with simultaneous expired gas assessment and echocardiography. Maximum oxygen uptake was comparable between groups (ASD 32.7±7.7 mL O2/kg per minute, controls 35.2±7.5 mL O2/kg per minute, P=0.3), as was cardiac index at both rest and peak exercise. In contrast, pulmonary artery wedge v wave pressures were increased at rest and peak exercise (rest: ASD 14±4 mm Hg, controls 10±5 mm Hg, P=0.01; peak: ASD 25±9 mm Hg, controls 14±9 mm Hg, P=0.0001). The right atrial v wave pressures were increased at rest but not at peak exercise. The transmural filling pressure gradient (TMFP) was higher at peak exercise among patients with ASD (10±6 mm Hg, controls 7±3 mm Hg, P=0.03). One third of patients with ASD demonstrated an abnormal hemodynamic exercise response defined as mean pulmonary artery wedge pressure ≥25 mm Hg and/or mean pulmonary artery pressure ≥35 mm Hg at peak exercise. These patients had significantly elevated peak right and left atrial a wave pressures, right atrial v wave pressures, pulmonary artery wedge v wave pressures, and transmural filling pressure compared with both controls and patients with ASD with a normal exercise response.ConclusionsPatients with corrected ASD present with elevated right and in particular left atrial pressures at rest and during exercise despite preserved peak exercise capacity. Abnormal atrial compliance and systolic atrial function could predispose to the increased long‐term risk of atrial fibrillation.Registration Informationclinicaltrials.gov. Identifier: NCT03565471.

Current Limitations of Invasive Exercise Hemodynamics for the Diagnosis of Heart Failure With Preserved Ejection Fraction.

Exercise hemodynamics can differentiate heart failure with preserved ejection fraction (HFpEF) from noncardiac dyspnea. However, respiratory pressure swings may impact hemodynamic measurements, potentially leading to misdiagnosis of HFpEF. Moreover, threshold values for abnormal hemodynamic response indicative of HFpEF are not universally accepted. Thus, we sought to evaluate the impact of respiratory pressure swings on hemodynamic data interpretation as well as the concordance among 3 proposed exercise hemodynamic criteria for HFpEF: (1) end-expiratory pulmonary artery wedge pressure (PAWPexp) ≥25 mm Hg; (2) PAWPexp/cardiac output slope >2 mm Hg/L per minute; and (3) respiratory-averaged (avg) mean pulmonary artery pressure >30 mm Hg, total pulmonary resistanceavg >3 WU, PAWPavg ≥20 mm Hg. Fifty-seven patients with unexplained dyspnea (70% women, 70±9 years) underwent exercise cardiac catheterization. The difference between end-expiratory and averaged hemodynamic values, as well as the concordance among the 3 hemodynamic definitions of HFpEF, were assessed. End-expiratory hemodynamics measurements were higher than values averaged across the respiratory cycle. During exercise, a larger proportion of patients exceeded the threshold of 25 mm Hg for PAWPexp rather than for PAWPavg (70% versus 53%, P<0.01). The concordance of 3/3 HFpEF exercise hemodynamic criteria was recorded in 70% of patients. PAWPexp/cardiac output slope identified HFpEF more frequently than the other 2 criteria (81% versus 64% to 69%), incorporating over 97% of abnormal responses to the latter. Patients with 3/3 positive criteria had worse clinical, gas-exchange, and hemodynamic profiles. Respiratory pressure swings impact on the exercise hemodynamic definitions of HFpEF that provide discordant results in 30% of patients. Equivocal diagnoses of HFpEF might be limited by adopting the most sensitive and inclusive criterion alone (ie, PAWPexp/cardiac output slope).

Inducible Nitric Oxide Synthase Gene Expression and Diastolic Function in Heart Transplant Recipients

Purpose A pulmonary wedge pressure >18 mmHg following volume load has been proposed as a partition value for the detection of HFpEF. In both experimental and clinical settings, the hemodynamic changes in filling pressures have been attributed to a nitric oxide(NO)-mediated rightward shift of the pressure-volume relationship. The present study investigates the hemodynamic response to a volume challenge upon diastolic function in heart transplant(HTx) recipients and examines the role of inducible nitric oxide synthase(iNOS) gene expression on diastolic function changes. Methods 36 HTx recipients with normal left ventricular function (ejection fraction[EF]: 61 ± 12%) and without rejection and graft vasculopathy underwent right heart catheterization for the measurement of the degree of hemodynamic response to volume loading after saline infusion of 7 mL/kg over 10 min. Pulmonary capillary wedge pressure(PCWP), right atrial pressure(RAP), and mean pulmonary artery pressure(PA) were measured, following which the PCWP and stroke volume index(SVI) were used for Starling(SVI/PCWP) curve construction. Pts were categorized into the normal (group A, n=20) and abnormal hemodynamics (group B, n=16, PCWP >15 mmHg at rest or >18 mmHg following volume load) groups. For the establishment of the potential role of NO as a mediator of hemodynamic response, the iNOS endomyocardial gene expression level was measured . Results No differences were observed in terms of donor and recipient age, baseline hemodynamic parameters, and EF between both groups. Volume load significantly increased PCWP and PA in both groups, without any significant change in blood pressure or heart rate. Saline infusion was associated with a significant increase in SVI in group A but not group B. Moreover, in group A, the Starling curves revealed a higher SVI at any given PCWP. Group A exhibited significantly higher iNOS gene expression levels than Group B. Conclusion In HTx, rapid saline infusion increases the filling pressure and unmasks the presence of left ventricular diastolic dysfunction. Interestingly, pts with an abnormal hemodynamic response show a blunted Frank-Starling response, as evidenced by the higher PCWP and lack of SVi increase at any given PCWP. The higher iNOS gene expression level in our control group suggests the potential role of NO as a mediator of diastolic function in heart Tx patients.

Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Arterial Stiffness and Abnormal Left Ventricular Hemodynamic Responses During Exercise

BackgroundArterial stiffness is thought to contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). We sought to examine arterial stiffness in HFpEF and hypertension and investigate associations of arterial and left ventricular hemodynamic responses to exercise. Methods and ResultsA total of 385 symptomatic individuals with an EF of ≥50% underwent upright cardiopulmonary exercise testing with invasive hemodynamic assessment of arterial stiffness and load (aortic augmentation pressure, augmentation index, systemic vascular resistance index, total arterial compliance index, effective arterial elastance index, and pulse pressure amplification) at rest and during incremental exercise. An abnormal hemodynamic response to exercise was defined as a steep increase in pulmonary capillary wedge pressure relative to cardiac output (∆PCWP/∆CO > 2 mm Hg/L/min). We compared rest and exercise measures between HFpEF and hypertension in multivariable analyses. Among 188 participants with HFpEF (mean age 61 ± 13 years, 56% women), resting arterial stiffness parameters were worse compared with 94 hypertensive participants (mean age 55 ± 15 years, 52% women); these differences were accentuated during exercise in HFpEF (all P ≤ .0001). Among all participants, exercise measures of arterial stiffness correlated with worse ∆PCWP/∆CO. Specifically, a 1 standard deviation higher exercise augmentation pressure was associated with 2.15-fold greater odds of abnormal LV hemodynamic response (95% confidence interval 1.52–3.05; P < .001). Further, exercise measures of systemic vascular resistance index, elastance index, and pulse pressure amplification correlated with a lower peak oxygen consumption. ConclusionsExercise accentuates the increased arterial stiffness found in HFpEF, which in turn correlates with left ventricular hemodynamic responses. Unfavorable ventricular–vascular interactions during exercise in HFpEF may contribute to exertional intolerance and inform future therapeutic interventions.

Headache and Left Ventricular Efficiency After Transcatheter Closure of Atrial Septal Defect.

This study aimed to clarify the relationship between migraine-like headache and ventriculo-arterial coupling after transcatheter closure of the atrial septal defect in children. We hypothesized that migraine headache after defect closure would be related to an abnormal hemodynamic response against an increased left ventricular filling. A retrospective cohort study. We calculated the end-ventricular systolic elastance (Ees), effective arterial elastance (Ea), and ventricular energy efficiency approximated based on echocardiography before and after defect closure, and compared these parameters between the subjects with and without headache after defect closure. A total of 167 subjects were studied. Age at the procedure, defect diameter, and pulmonary to systemic blood flow ratio were 11 (9-17) years, 12.8 (9.2-16.0) mm, and 1.8 (1.6-2.3), respectively. We identified 47 (28%) subjects with migraine headache after defect closure. Although there was no significant difference in the Ees, Ea, and ventricular energy efficiency before defect closure between the groups, the Ees (4.0 [3.4-4.9] vs 4.8 [3.7-6.1], P=.014) and ventricular energy efficiency (0.79 [0.76-0.82] vs 0.83 [0.79-0.85], P=.001) after defect closure in subjects with headache were significantly lower than those in subjects without headache. Migraine headache after defect closure was significantly associated with age (odds ratio: 0.97, 95% confidential interval: 0.94-1.00, P=.036) and a decrease in the ventricular energy efficiency after defect closure (odds ratio: 6.42, 95% confidential interval: 2.76-14.90, P<.001). A loss of ventricular energy efficiency was common in pediatric subjects with migraine-like headache after transcatheter closure of the atrial septal defect, which suggested that the left ventricular function maladaptation was related to headache development after defect closure. We advocate that an impaired ventriculo-arterial coupling may be one of the mechanisms for developing attacks in not only this population but also in other patients with migraine.

Interrater Reliability Across 7 Established Risk Stratification Protocols in Cardiac Rehabilitation

ObjectiveTo analyze the interrater agreement among physiotherapists in using 7 risk stratification (RS) protocols to evaluate participants of cardiac rehabilitation (CR) and the main factors associated with disagreements that emerged during the RS process. DesignCross-sectional observational study. SettingOutpatient rehabilitation center. ParticipantsPatients (N=72) enrolled in CR with a diagnosis of cardiovascular disease or cardiovascular risk factors. Mean age was 65.62±12.14 y, and mean body mass index (calculated as weight in kilograms divided by height in meters squared) was 29.18±4.56. InterventionsNot applicable. Main Outcome MeasuresThe main outcome was to the agreement between 2 physiotherapists in the patients’ RS process, using 7 protocols established in the literature for use in CR: American Association of Cardiovascular and Pulmonary Rehabilitation, American College of Sports Medicine, American Heart Association, Sociedade Brasileira de Cardiologia, Sociedad Española de Cardiología, and Société Française de Cardiologie. In addition, the main disagreement factors were assessed. ResultsInterrater agreement was classified as moderate-to-good in the 7 included RS protocols (kappa index between 0.53-0.76). The most important aspects that led to disagreement between physiotherapists were reported in 5 categories. The protocol with the greater agreement index was the American College of Sports Medicine (93.10%; n=67), and the one with the greater disagreement was the American Association of Cardiovascular and Pulmonary Rehabilitation (27.80%; n=20). ConclusionsModerate-to-good interrater agreement among physiotherapists in using 7 RS protocols was observed. Major disagreements were the definition of abnormal hemodynamic responses, rhythm disorders, left ventricular dysfunction, and interpretation of the patient’s clinical characteristics.

Interictal hemodynamic abnormality during motor activation in sporadic hemiplegic migraine: An explorative study

IntroductionThe motor weakness in sporadic hemiplegic migraine (SHM) is a poorly understood aura manifestation. Cortical spreading depression affecting motor excitability and alterations of neurovascular coupling may be integral to the development of migraine aura. MethodsWe studied 10 right-handed SHM patients and 17 healthy controls with functional near-infrared spectroscopy (fNIRS) in the interictal period. Subjects performed a finger opposition task and had real time determination of oxyhemoglobin (OxyHb) and deoxyhemoglobin (deOxyHb) changes. Recordings were completed with 10 left and 10 right sided cortical channels. ResultsMean baseline to peak changes were significantly reduced in SHM patients as compared to controls bilaterally only for OxyHb measurements in the anteromedial channels. Mean time to peak changes were significant delayed in SHM patients compared to controls bilaterally largely for OxyHb measurements in the posterolateral channels, with the exception of 2 recording channels. ConclusionsOur findings suggest presence of abnormal interictal hemodynamic responses to increased metabolic demands during motor activation in SHM. These bilateral cerebrovascular changes involve OxyHb to a much larger degree than deOxyHb. Baseline to peak changes were evident more in the anteromedial channels, whereas time to peak changes were more evident in the posterolateral channels. These findings suggest that oxygen inflow into specific brain regions may be defective in SHM as opposed to oxygen utilization. Our findings suggest that in SHM, enduring hemodynamic deficits in response to an impending motor task are evident, which can be further explored in future studies, and possibly therapeutic trials.