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In the hands of ohm: hemodynamic aspects in pulmonary hypertension
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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 PCWPPLL. 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.  

Place, publisher, year, edition, pages
Umeå: Umeå university , 2019. , p. 70
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2031
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
URN: urn:nbn:se:umu:diva-158842ISBN: 978-91-7855-059-3 (print)OAI: oai:DiVA.org:umu-158842DiVA, id: diva2:1314969
Public defence
2019-06-05, Sal C, 9 tr, NUS, Umeå, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2019-05-15 Created: 2019-05-10 Last updated: 2019-05-14Bibliographically approved
List of papers
1. Pulmonary artery acceleration time in identifying pulmonary hypertension patients with raised pulmonary vascular resistance
Open this publication in new window or tab >>Pulmonary artery acceleration time in identifying pulmonary hypertension patients with raised pulmonary vascular resistance
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2013 (English)In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 14, no 9, p. 890-897Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: In patients with pulmonary hypertension (PH), ascertaining raised vascular resistance as a cause is a clinical objective, for which various Doppler-based measurements have been proposed, but with modest accuracy. We hypothesize that pulmonary acceleration time (PAcT) and the ratio of PAcT/peak pulmonary artery systolic pressure (PASP) reflect better the extent of the vascular resistance, compared with other available methods, and can differentiate accurately between pre- and post-capillary PH.

METHODS AND RESULTS: We investigated 56 patients (mean age 61 ± 13 years, 23 males) in a simultaneous echocardiography and right heart catheterization (RHC) study. Based on the RHC, pulmonary vascular resistance (PVR), and pulmonary capillary wedge pressure (PCWP), patients were divided into four groups: Group 1 = normal PVR [<3 WU (Wood units)] and PCWP (<12 mmHg), Group 2 = raised PVR but normal PCWP, Group 3 = raised PVR and PCWP; and Group 4 = normal PVR but raised PCWP. We used spectral Doppler to measure PAcT (corrected for heart rate) and to estimate PASP (peak tricuspid regurgitation pressure drop + estimated right atrial pressure of 7 mmHg). We also tested other available methods for assessing PVR. There were small age differences between patient groups but no age difference between Groups 2 and 4. PAcT and PAcT/PASP were both significantly (P = 0.008) reduced in Groups 2 and 3 compared with Groups 1 and 4. PAcT ≤90 had an 84% sensitivity and an 85% specificity in identifying patients with PVR ≥3 WU with a positive and a negative predictive value of 88% and 81%, respectively. The non-linear relationship between PVR and PAcT gave a quadratic r = 0.61, P < 0.001. ROC curve analysis showed PAcT having the best accuracy (83%) in detecting a PVR ≥3 WU.

CONCLUSION: PAcT <90 ms can serve as a strong non-invasive predictor of PVR >3 WU, which could differentiate patients with pre- and post-capillary PH.

Keywords
Amyloidosis, Cardiomyopathy, Familial amyloid polyneuropathy, Methodology, Neuropathy, Registry, Transthyretin
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-65109 (URN)10.1093/ehjci/jes309 (DOI)000322953100011 ()23295626 (PubMedID)
Available from: 2013-02-15 Created: 2013-02-06 Last updated: 2019-05-10Bibliographically approved
2. Left Atrial Intrinsic Strain Rate Correcting for Pulmonary Wedge Pressure Is Accurate in Estimating Pulmonary Vascular Resistance in Breathless Patients
Open this publication in new window or tab >>Left Atrial Intrinsic Strain Rate Correcting for Pulmonary Wedge Pressure Is Accurate in Estimating Pulmonary Vascular Resistance in Breathless Patients
2016 (English)In: Echocardiography, ISSN 0742-2822, E-ISSN 1540-8175, Vol. 33, no 8, p. 1156-1165Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keywords
echocardiography, strain rate, left atrium
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-120756 (URN)10.1111/echo.13226 (DOI)000383354900005 ()27144613 (PubMedID)
Available from: 2016-05-20 Created: 2016-05-20 Last updated: 2019-05-10Bibliographically approved
3. Passive leg lifting in heart failure patients predicts exercise induced rise in left ventricular filling pressures
Open this publication in new window or tab >>Passive leg lifting in heart failure patients predicts exercise induced rise in left ventricular filling pressures
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(English)Manuscript (preprint) (Other academic)
Keywords
Passive leg lifting, exercise, elevated filling pressures, pulmonary hypertension, heart failure
National Category
Respiratory Medicine and Allergy
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-158841 (URN)
Available from: 2019-05-10 Created: 2019-05-10 Last updated: 2019-05-14
4. Can Doppler echocardiography estimate raised pulmonary capillary wedge pressure provoked by passive leg lifting in suspected heart failure?
Open this publication in new window or tab >>Can Doppler echocardiography estimate raised pulmonary capillary wedge pressure provoked by passive leg lifting in suspected heart failure?
Show others...
2019 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, no 2, p. 128-134Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
deformation, passive leg lifting, pulmonary capillary wedge pressures, strain rate
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-152550 (URN)10.1111/cpf.12547 (DOI)000458316200003 ()30298591 (PubMedID)
Funder
Swedish Heart Lung Foundation
Available from: 2018-10-11 Created: 2018-10-11 Last updated: 2019-05-10Bibliographically approved

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