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Background: Assessment of pulmonary vascular resistance (PVR) is critical for accurate diagnosis and optimal pharmacotherapy in pulmonary hypertension. We aimed to test the diagnostic performance of a novel, Doppler-based method to evaluate PVR based on Ohm’s law (PVR_echo) using pragmatic estimates of pulmonary capillary wedge pressure (PCWP).

Methods and results: Simultaneous right heart catheterization (RHC) and echocardiography was performed in a derivation cohort of 111 patients in sinus rhythm referred for PH evaluation and PVR_echo independently validated in 238 patients. PVR_echo was calculated using pulmonary artery mean pressure estimates (PAMP_echo) obtained from peak tricuspid gradient employing a fixed right atrial pressure estimate, PCWP_echo was estimated as 10 or 20 mmHg using age-related mitral E/A cut-offs and cardiac output from left ventricular outflow. In the derivation cohort, both PAMP_echo and PCWP_echo estimates demonstrated excellent agreement with catheterization measurements. PVR_echo was highly feasible, demonstrated negligible bias and excellent agreement with PVR_RHC (Bias = −0.58, SD 2.2 mmHg) and outperformed the Abbas method to identify PVR_RHC > 3WU (AUC = 0.85 vs. 0.70; p = 0.02). In the validation cohort, PVR_echo preserved good invasive agreement with negligible bias, displayed strong diagnostic performance (AUC = 0.84) and significant ability to distinguish isolated post-capillary from combined post- and pre-capillary pulmonary hypertension (PH) subgroups (AUC = 0.77).

Conclusion: PVR_echo based on Ohm’s law employing pragmatic estimates of PCWP_echo demonstrates excellent agreement with invasive reference standard measurements and strong diagnostic ability to identify elevated PVR_RHC. This novel approach may be useful during therapy selection to distinguish PH hemodynamic subgroups.

AIMS: This study aimed to investigate the incremental value offered by left atrial reservoir strain (LAS_r) to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) diastolic algorithm to identify elevated left ventricular (LV) filling pressure in patients with preserved ejection fraction (EF).

METHODS AND RESULTS: Near-simultaneous echocardiography and right heart catheterization were performed in 210 patients with EF ≥50% in a large, dual-centre study. Elevated filling pressure was defined as invasive pulmonary capillary wedge pressure (PCWP) ≥15 mmHg. LAS_r was evaluated using speckle-tracking echocardiography. Diagnostic performance of the ASE/EACVI diastolic algorithm was validated against invasive reference and compared with modified algorithms incorporating LAS_r. Modest correlation was observed between E/e', E/A ratio, and LA volume index with PCWP (r = 0.46, 0.46, and 0.36, respectively; P < 0.001 for all). Mitral e' and TR peak velocity showed no association. The ASE/EACVI algorithm (89% feasibility, 71% sensitivity, 68% specificity) demonstrated reasonable ability (AUC = 0.69) and 68% accuracy to identify elevated LV filling pressure. LAS_r displayed strong ability to identify elevated PCWP (AUC = 0.76). Substituting TR peak velocity for LAS_r in the algorithm (69% sensitivity, 84% specificity) resulted in 91% feasibility, 81% accuracy, and stronger agreement with invasive measurements. Employing LAS_r as per expert consensus (71% sensitivity, 70% specificity) and adding LAS_r to conventional parameters (67% sensitivity, 84% specificity) also demonstrated greater feasibility (98% and 90%, respectively) and overall accuracy (70% and 80%, respectively) to estimate elevated PCWP.

CONCLUSIONS: LAS_r improves feasibility and overall accuracy of the ASE/EACVI algorithm to discern elevated filling pressures in patients with preserved EF.

Accurate assessment of pulmonary artery (PA) pressures is integral to diagnosis, follow-up and therapy selection in pulmonary hypertension (PH). Despite wide utilization, the accuracy of echocardiography to estimate PA pressures has been debated. We aimed to evaluate echocardiographic accuracy to estimate right heart catheterization (RHC) based PA pressures in a large, dual-centre hemodynamic database. Consecutive PH referrals that underwent comprehensive echocardiography within 3 h of clinically indicated right heart catheterization were enrolled. Subjects with absent or severe, free-flowing tricuspid regurgitation (TR) were excluded. Accuracy was defined as mean bias between echocardiographic and invasive measurements on Bland–Altman analysis for the cohort and estimate difference within ± 10 mmHg of invasive measurements for individual diagnosis. In 419 subjects, echocardiographic PA systolic and mean pressures demonstrated minimal bias with invasive measurements (+ 2.4 and + 1.9 mmHg respectively) but displayed wide limits of agreement (− 20 to + 25 and − 14 to + 18 mmHg respectively) and frequently misclassified subjects. Recommendation-based right atrial pressure (RAP) demonstrated poor precision and was falsely elevated in 32% of individual cases. Applying a fixed, median RAP to echocardiographic estimates resulted in relatively lower bias between modalities when assessing PA systolic (+ 1.4 mmHg; 95% limits of agreement + 25 to − 22 mmHg) and PA mean pressures (+ 1.4 mmHg; 95% limits of agreement + 19 to − 16 mmHg). Echocardiography accurately represents invasive PA pressures for population studies but may be misleading for individual diagnosis owing to modest precision and frequent misclassification. Recommendation-based estimates of RAPmean may not necessarily contribute to greater accuracy of PA pressure estimates.

Aim: The aim of this study was to assess PCWP with passive leg-lifting (PLL) and exercise, in two groups of patients presenting with normal left ventricular ejection fraction (LVEF); one group with elevated NT-proBNP (eBNP), and one with normal NT-proBNP (nBNP) plasma concentration.

Methods and results: Fifty-one patients with eBNP (NT-proBNP ≥ 125 ng/l) and LVEF > 50%, were investigated and compared with 34 patients with nBNP (NT-proBNP < 125 ng/l) and LVEF > 50%. Both groups underwent right heart catheterization (RHC) at rest, PLL and exercise. From RHC, mean pulmonary arterial pressure (mPAP), cardiac output (CO), and PCWP were measured. All nBNP patients had PCWP < 15 mmHg at rest, and a PCWP of < 25 mmHg with PLL and during exercise. Patients with eBNP had higher (p < 0.01) resting mPAP, PCWP, and mPAP/CO. These values increased with exercise; however, CO increased less in comparison with nBNP patients (p = 0.001). 20% of patients with eBNP had a PCWP > 15 mmHg at rest, this percentage increased to 47% with PLL and 41% had a PCWP > 25 mmHg during exercise. Of those with PCWP > 25 mmHg during exercise, 91% had a PCWP > 15 mmHg with PLL. A PCWP > 15 mmHg on PLL had a 91% sensitivity and 92% specificity in predicting exercise-induced PCWP of > 25 mmHg.

Conclusion: In patients presenting with eBNP, PLL can predict which patients will develop elevated PCWP with exercise. These findings highlight the role of stress assessment.

AIMS: Non-invasive estimation of left ventricular filling pressure (LVFP) during stress is important for explaining exertional symptoms in patients with heart failure (HF). The aim of this study was to evaluate ability of Doppler echocardiographic measures of elevated LVFP with passive leg lifting (PLL) in patients with suspected HF.

METHODS: Twenty-nine patients with clinical signs of HF who underwent simultaneous Doppler echocardiography and right heart catheterization (RHC) at rest and during PLL were consecutively investigated. Seventeen patients had normal PCWP (≤15 mmHg) at rest and during PLL and 12 with normal PCWP at rest but >15 mmHg with PLL. Conventional echo and 2D strain were used to assess early diastolic blood flow velocity (E), LV strain rate during early diastole (LVSRe), left atrial SR during atrial contraction (LASRa) and myocardial tissue Doppler velocities to assess lateral e' and further calculate E/e' and E/LVSRe and their relationship with PCWP, at rest and during PLL.

RESULTS: Resting LAVI (β = 0·45, P = 0·009) and LASRa (β = -0·51, P = 0·004) were independently related to PCWP during PLL. Also, LASRa (β = -0·77, P<0·001), E/e' (β = 0·40, P = 0·04) and E/LVSRe (β = 0·47, P = 0·021) during PLL correlated with PCWP during PLL. Multiple regression analysis identified E/LVSRe (β = 0·46, P = 0·001) and LASRa (β = -0·58, P = 0·002) during PLL as being independently associated with PCWP during PLL.

CONCLUSION: Left atrial volume and myocardial contraction (LASRa) at rest both predict unstable LV filling pressures measured as raised PCWP when provoked by PLL. Furthermore, LASRa at PLL seems to have the strongest association to PCWP during PLL.

Congestive heart failure (CHF) is one of the most challenging diseases in terms of health care demand and mortality, in the western world. Despite major breakthroughs in the fields of diagnosis and treatment over the three last decades, the management of CHF still remains challenging.

CHF is defined as inability of the heart to supply sufficient blood flow to meet the needs of the body. This definition however, may be an oversimplification of a complex pathophysiological process since patients with overt CHF may have normal, or even supernormal cardiac output at the expense of increased filling pressures, which subsequently leads to the development of post capillary pulmonary hypertension (PH). In the presence of advanced CHF, clinical signs and symptoms are obvious at rest. However, the majority of affected individuals do not experience any discomfort at rest and may demonstrate normal findings when assessed. Small increases in systemic blood pressure and or venous return, caused by activity may result in severe elevation of filling pressures if left ventricular compliance is significantly decreased. This example highlights the need to perform cardiac investigations during stress to provoke symptoms. Increased pulmonary vascular resistance (PVR), commonly found in pre-capillary PH, is a condition that shares many symptoms with CHF, and is also associated with poor prognosis. Even though the disease is located within the lung vessels, it is highly important and challenging task differentiating pre- and post-capillary PH. Since treatment differs considerably and may be detrimental in case of misdiagnosis, additional sensitive and reliable screening methods are crucial to aid in differentiation.

Methods: Out of the four studies included in this thesis, three were conducted solely at Norrland’s University Hospital, while patients in the third study were recruited and examined at Uppsala Akademiska Hospital. All included patients had idiopathic dyspnea and were admitted for right heart catheterization (RHC), which is gold standard with regards to hemodynamics. Echocardiographic examinations were performed simultaneously with RHC, except in the Uppsala study, wherein echocardiography were performed within 3 days to the RHC.

Echo-Doppler derived pulmonary artery acceleration time (PAcT) is an easily assessed parameter, indicating elevated pulmonary artery systolic pressure (PASP) and pulmonary artery resistance (PVR). PAcT was tested as a screening method for identification and differentiation of pre and post- capillary PH in a cohort of 56 patients (study 1).

The ability to calculate PVR non-invasively, using novel echocardiographic measurements, was made by replacing the invasive pressure and flow components that constitutes the foundation of the PVR = (mean pulmonary artery pressure – Pulmonary capillary wedge pressure (PCWP)) /cardiac output), with novel echocardiographic measurements. PVR = mPAP-Chemla – Left atrial strain rate during atrial systole (LASRa) / Cardiac Output-Echo (study 2).

Invasively measured left ventricular filling pressure in response to passive leg lifting, and its ability to predict pathological increase in left ventricular filling pressures during supine bicycling, was tested in a population of 85 patients with normal left ventricular ejection fraction (LVEF) and suspicion of CHF based on NT-proBNP levels alone were investigated (Study 3).

Finally, an evaluation of standard and novel Doppler echocardiographic parameters, potentially useful in identifying patients who may develop increased filling pressures during passive leg lifting (PLL), was carried out (study 4).

Results:

Study 1: PAcT correlated negatively with pulmonary artery systolic pressure (PASP) (r = -0.60, p < 0.001) and PVR (r = -0.57, p < 0.001). PAcT of <90 ms had a sensitivity of 84% and a specificity of 85% in identifying patients with PVR ≥ 3.0 WU. Regardless of normal or elevated left sided filling pressures, PAcT differed significantly in patients with normal, compared to those with elevated levels of, PVR (p < 0.01). A significant difference was also found on comparison of the PAcT/PASP ratio (p < 0.01), with a lower ratio among patients with PVR ≥ 3.0. WU.

Study 2: We prospectively used Doppler and 2D echocardiography in 46 patients with sinus rhythm which revealed that left atrial strain rate during atrial systole (LASRa) had the highest significant positive correlation with PCWP (r² = 0.65, P < 0.001). By adopting a linear line of best-fit, LASRa may therefore be substituted for PCWP. Subsequently, LASRa was substituted into the PVR equation. This novel echocardiographically derived PVR calculation, significantly correlated with RHC generated PVR values (r² = 0.69, P < 0.001) and minor drift (+0.1WU) when assessed by Bland Altman analysis.

Study 3: Only 22% (11/51) of patients with elevated NT-proBNP had PCWP above normal levels at rest. However, in response to PLL, 47% of patients developed elevated PCWP, and the majority of this 47% subsequently developed pathological pressure levels while performing supine cycling exercise. Thus, the likelihood of developing high LVFPs during exercise could be determined by PLL, with a sensitivity and specificity of 90%.

Study 4: At rest, left atrial volume indexed to body mass index (BMI) (LAVI) and mitral deceleration time (DT) were independently related to PCWP during PLL. However, during PLL univariate regression analysis revealed LASRa (β = -0.77, P <0,001) and E/LVSRe (β = 0.47, P < 0,021) most related to PCWP_PLL. Multiple regression analysis fortified LASRa and E/LVSRe as relevant independent parameters useful in the assessment of filling pressure during PLL.

Conclusion: A PAcT < 90ms is strongly suggestive of increased PVR (>3.0 WU). Based on study 1, there is clear evidence suggesting that these findings apply irrespective of LVFPs. PAcT can potentially serve as a rapid screening tool for estimation of PVR, however, is not useful if the exact level of PVR is required. In this case, an established PVR calculation method is preferred, and could be performed with higher precision by inclusion of echocardiography derived LASRa as a surrogate measure of PCWP. Insufficient LV compliance results in the inability to cope with increased cardiac preload. Nt-proBNP is secreted when the myocardium is stretched, however only a small portion of patients within the CHF group (study 3) had a high PCWP at rest. Nearly half of the study population with elevated NT-proBNP showed increased PCWP during PLL, which is indicative of underlying ventricular stiffness. By performing this preload increasing maneuver, patients predisposed to developing high filling pressure during supine cycling could be identified with high sensitivity and specificity. Echocardiography, in comparison with RHC, is more accessible, safer and requires less resources and time, thus is an appealing option in the quest to identify additional, non-invasive methods reflective of invasive pressures, which could be useful in the assessment of filling pressure during different loading conditions. LAVI at rest, LASRa and E/LVSRe during PLL, proved independently related to PCWP during PLL.  

In pulmonary hypertension (PH), the right heart dysfunction is a strong predictor of adverse clinical outcome, while the role of the left heart is not fully determined. The aim of this study was to identify predictors of mortality in precapillary PH including measures of both right and left heart function. We studied 34 patients (mean age 64 ± 13, range 31-82 years, 24 females) with precapillary PH, all of whom underwent detailed Doppler echocardiographic examination of the right and left heart function using conventional and speckle-tracking echocardiography. Patients were followed up for up to 8 years (mean 4·2 ± 1·9 years). At follow-up, 16 patients survived. Left ventricular (LV) filling time (P = 0·007), pulmonary artery acceleration time (P = 0·009), right atrial pressure (RAP) (P<0·001) and tricuspid regurgitation (TR) severity (P = 0·007) were worse in the deceased group. RV global longitudinal strain (GLS) (P = 0·001), RAP (P≤0·001), LV filling time (P<0·001) and TR severity (P<0·001) were the most accurate predictors, having the largest AUC (>0·65) and carried the highest risk for mortality (P<0·001 for all). The strongest predictors of mortality in precapillary PH indirectly reflect both left and right heart dysfunction including atrial structure and function disturbances. While an interaction pattern is observed, it needs to be confirmed in a larger cohort.

OBJECTIVES: We hypothesized that left atrial deformation during atrial systole (LASRa) correlates with pulmonary capillary wedge pressure (PCWP), thus enabling echo-derived pulmonary vascular resistance (PVR) estimation in a wide range of different subsets of patients.

BACKGROUND: Various etiologies of pulmonary hypertension (PH) have different mechanisms and treatments for breathlessness. Irrespective of the location of the underlying pulmonary vascular pathology, pre- or postcapillary, the resulting PH is fairly easy to assess by Doppler echocardiography, but PVR remains a challenge.

METHODS: We prospectively included 46 patients (mean age 61 ± 13 years) in sinus rhythm, who underwent right heart catheterization because of dyspnea. According to the NICE guidelines classification, 22 belonged to group 1 pulmonary artery hypertension (PAH), 19 belonged to group 2 congestive heart failure (CHF), 1 belonged to group 4 chronic thromboembolic pulmonary hypertension (CTEPH), and 4 had normal hemodynamics. Simultaneous Doppler echocardiography using spectral, tissue Doppler, and speckle tracking echocardiography techniques for assessing LA structure and function was performed.

RESULTS: PCWPrhc correlated with LASRa (r(2) = 0.65, P < 0.001). PCWPecho was calculated using the equation (PCWPecho = 26.12 - 11.09 × LASRa), and the resulting PVR echo strongly correlated with the respective catheter-based measurements PVRrhc (r(2) = 0.69. P < 0.001) with a sensitivity of 85% and specificity of 74% identifying a PVR ≥ 3 WU.

CONCLUSIONS: Left atrial strain rate during atrial systole correlates closely with pulmonary capillary wedge pressure and consequently the calculated pulmonary vascular resistance, irrespective of the etiology of PH.