Symptom Persistence Despite Improvement in Cardiopulmonary Health - Insights from longitudinal CMR, CPET and lung function testing post-COVID-19

Background The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19. Methods Fifty-eight patients and thirty matched controls underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months. Findings At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of inflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pVO2) on CPET. By 6 months, 53% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4.3 mls/m2, P=0.005) decreased and RV ejection fraction (+3.2%, P=0.0003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak VO2, although better, were abnormal in patients versus controls. 31% had reduced pVO2 secondary to fatigue and submaximal tests. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures. Interpretation In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health. Funding NIHR Oxford and Oxford Health BRC, Oxford BHF CRE, UKRI and Wellcome Trust.

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P6325Gas exchange improvements during exercise correlate with hemodynamic changes in heart failure patients with a left ventricular assist device

European Heart Journal ◽

10.1093/eurheartj/ehz746.0922 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

K Seuthe ◽

M Morosin ◽

H Smail ◽

F Gerhardt ◽

A Simon ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Output ◽

Cardiopulmonary Exercise Test ◽

Left Ventricular ◽

Peak Oxygen Consumption ◽

Ventricular Assist ◽

Heart Failure Patients ◽

Left Ventricular Assist

Abstract Background The implantation of left ventricular assist devices (LVAD) has established its role in therapy for patients with end stage heart failure. Benefits in survival as well as an improved quality of life, compared to optimized medical therapy (OMT) alone, has been proven. There are limited data in the literature on the metabolic changes during exercise in LVAD patients, and in most studies no increase in peak oxygen consumption on cardiopulmonary exercise test (CPET) could be shown early after surgery. However, recent data suggests an improvement in peak oxygen uptake (VO2) as a late effect after rehabilitation. To further investigate these findings we sought to analyse CPET data from patients before LVAD implantation as well as in the early and late follow up in correlation with hemodynamic changes at these times. Methods We collected and retrospectively analysed data of heart failure patients who had undergone LVAD implantation, and in whom a right heart catheterization, a cardiopulmonary exercise test and an echocardiography had been performed at time before, as well as 6 Months and 12 months after LVAD implantation, respectively. Results Data of 43 patients implanted with an LVAD between 2011 and 2017 were analysed. There was significant improvement in cardiac output (3,2 vs 4,3 L/min, p<0,001) and VE/VCO2 slope (46 vs 38, p=0,001) 6 months after LVAD implant as well as a significant reduction in PCWP (26 vs 11 mmHg, p<0,001), PAP mean (40 vs 22 mmHg, p<0,001), RA mean (12 vs 8 mmHg, p=0,002) and PVR (4,2 vs 2,5 WU, p<0,001). However, there was no significant increase in peak VO2 after 6 months. 12 months after LVAD implantation there were no further significant changes in cardiac output, intracardiac pressures or VE/VCO2 slope, which all remained similar to the 6 months follow up. However, at that point, a significant increase in peak VO2 was seen, compared to baseline (1060 vs 1410ml/min, p=0,001) and to 6 months after surgery (Figure 1). Conclusion Cardiac output increases in heart failure patients early after LVAD implantation. Consequently, permanent ventricular off loading results in the reduction of intracardiac pressures and improvement in the VE/VCO2 slope 6 months after surgery. However, a significant rise in peak oxygen consumption could only be noted 12 months after surgery, suggesting either a delayed long-term effect of improved hemodynamics or other causes such as enhanced mobility or training due to improved quality of life.

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Longitudinal changes in cardiac morphology and function in women with INOCA: results from repeat cardiac magnetic resonance imaging a median of 6 years apart

European Heart Journal ◽

10.1093/eurheartj/ehab724.0228 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

S K Zamani ◽

J Wei ◽

A C Kwan ◽

D S Berman ◽

C Shufelt ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Cardiac Magnetic Resonance ◽

Ejection Fraction ◽

Strain Rate ◽

Volume Index ◽

Resonance Imaging ◽

Cardiac Morphology ◽

End Diastolic Volume ◽

And Function

Abstract Background Women with signs and symptoms of ischemia but no obstructive coronary arteries (INOCA) are at increased risk of developing heart failure with preserved ejection fraction. The exact mechanism(s) driving disease progression, however, remains incompletely understood. Purpose To evaluate longitudinal changes in cardiac morphology and function across all four chambers of the heart, in women with INOCA. Methods To accomplish our goal, we leveraged 13 cases of repeat cardiac magnetic resonance imaging (cMRI), performed a median of 6 years apart (range: 3–11 years), in women with INOCA. Cardiac morphology and function were retrospectively assessed from conventional cine images using commercially available software (V5.11.1, CVI42, Circle Cardiovascular Imaging). Left and right ventricular (LV, RV, respectively) mass, volume, and ejection fraction were assessed using a series of short axis images spanning the base to apex. Left atrial (LA) volume was assessed using three orthogonal long-axis images, while right atrial (RA) area was assessed using a single horizontal long axis image. Concentricity was defined as the mass-to-end-diastolic volume ratio. Lastly, strain and strain rate were assessed in all four chambers by feature tracking analysis. Results Upon follow-up, LV and RV end-diastolic volume index (Figure 1A), LA volume index (from 36±5 to 32±5 mL/m2, P=0.02) and RA area index (from 11.3±1.6 to 9.6±2.0 cm2/m2, P=0.003) were significantly reduced. LV mass was preserved (Figure 1B), resulting in a significant increase in LV concentricity (from 0.59±0.07 to 0.64±0.09, P=0.02), together with an increase in LV ejection fraction (Figure 1C), and reduction in both longitudinal (Figure 1D) and circumferential (from 1.3±0.2 to 1.1±0.3 s-1, P=0.05) LV early diastolic strain rate. In contrast, RV mass was significantly reduced (Figure 1B), while RV concentricity (from 0.19±0.02 to 0.20±0.04) and ejection fraction (from 58±4 to 59±6) were preserved. Conclusions To our knowledge, this is the first study to evaluate long-term changes in cardiac morphology and function in women with INOCA. That LV early diastolic strain rate was reduced at follow-up, is consistent with a growing body of cross-sectional observations from our group and others, highlighting diastolic dysfunction as an important contributor of disease progression in this patient population. That we observed a discordant pattern of change between LV and RV concentricity is unique and warrants further consideration. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National heart, lung, and blood institute (NIH)

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Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome?

ERJ Open Research ◽

10.1183/23120541.00542-2020 ◽

2020 ◽

Vol 6 (4) ◽

pp. 00542-2020 ◽

Cited By ~ 10

Author(s):

Yvonne M.J. Goërtz ◽

Maarten Van Herck ◽

Jeannet M. Delbressine ◽

Anouk W. Vaes ◽

Roy Meys ◽

...

Keyword(s):

Healthcare Utilisation ◽

Median Number ◽

Anecdotal Evidence ◽

Persistent Symptoms ◽

Healthcare Needs ◽

Unmet Healthcare Needs ◽

Hospitalised Patients ◽

Multiple Symptoms ◽

Over Time

BackgroundMany patients with COVID-19 did not require hospitalisation, nor underwent COVID-19 testing. There is anecdotal evidence that patients with “mild” COVID-19 may complain about persistent symptoms, even weeks after the infection. This suggests that symptoms during the infection may not resolve spontaneously. The objective of this study was to assess whether multiple relevant symptoms recover following the onset of symptoms in hospitalised and nonhospitalised patients with COVID-19.MethodsA total of 2113 members of two Facebook groups for coronavirus patients with persistent complaints in the Netherlands and Belgium, and from a panel of people who registered on a website of the Lung Foundation Netherlands, were assessed for demographics, pre-existing comorbidities, health status, date of symptoms onset, COVID-19 diagnosis, healthcare utilisation, and the presence of 29 symptoms at the time of the onset of symptoms (retrospectively) and at follow-up (mean±sd 79±17 days after symptoms onset).ResultsOverall, 112 hospitalised patients and 2001 nonhospitalised patients (confirmed COVID-19, n=345; symptom-based COVID-19, n=882; and suspected COVID-19, n=774) were analysed. The median number of symptoms during the infection reduced significantly over time (median (interquartile range) 14 (11–17) versus 6 (4–9); p<0.001). Fatigue and dyspnoea were the most prevalent symptoms during the infection and at follow-up (fatigue: 95% versus 87%; dyspnoea: 90% versus 71%).ConclusionIn previously hospitalised and nonhospitalised patients with confirmed or suspected COVID-19, multiple symptoms are present about 3 months after symptoms onset. This suggests the presence of a “post-COVID-19 syndrome” and highlights the unmet healthcare needs in a subgroup of patients with “mild” or “severe” COVID-19.

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Heterogeneity of treatment response in bronchiectasis clinical trials

European Respiratory Journal ◽

10.1183/13993003.00777-2021 ◽

2021 ◽

pp. 2100777

Author(s):

Oriol Sibila ◽

Elena Laserna ◽

Amelia Shoemark ◽

Lidia Perea ◽

Diana Bilton ◽

...

Keyword(s):

Clinical Trials ◽

Lung Function ◽

Treatment Response ◽

Minimum Clinically Important Difference ◽

Clinical Parameters ◽

Clinically Important Difference ◽

Primary Endpoints ◽

The Relationship

IntroductionRecent randomised clinical trials (RCTs) in Bronchiectasis have failed to reach their primary endpoints, suggesting a need to reassess how we measure treatment response. Exacerbations, quality of life (QOL) and lung function are the most common endpoints evaluated in bronchiectasis clinical trials. We aimed to determine the relationship between responses in terms of reduced exacerbations, improved symptoms and lung function in bronchiectasis.MethodsWe evaluated treatment response in 3 RCTs that evaluated mucoactive therapy (inhaled Mannitol), an oral anti-inflammatory/antibiotic (Azithromycin) and an inhaled antibiotic (Aztreonam). Treatment response was defined by absence of exacerbations during follow-up, an improvement of QOL above the minimum clinically important difference (MCID) and an improvement in FEV1 of ≥100 mL from baseline.Measurements and main resultsCumulatively the three trials included 984 patients. Changes in FEV1, QOL and exacerbations were heterogeneous in all trials analysed. Improvements in QOL were not correlated to changes in FEV1 in the azithromycin and aztreonam trials (r=−0.17, p=0.1 and r=0.04, p=0.4) and weakly correlated in the mannitol trial (r=0.22, p<0.0001). An important placebo effect was observed in all trials, especially regarding improvements in QOL. Clinical meaningful lung function improvements were rare across all trials evaluated, suggesting that FEV1 is not a responsive measure in bronchiectasis.ConclusionsImprovements in lung function, symptoms and exacerbation frequency are dissociated in bronchiectasis. FEV1 is poorly responsive and poorly correlated with other key outcome measures. Clinical parameters are poorly predictive of treatment response suggesting the need to develop biomarkers to identify responders

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Abstract 19447: Correlation of Early Echocardiographic Right Ventricular Dimension and MRI Right Ventricular Volumes Late After Tetralogy of Fallot Repair

Circulation ◽

10.1161/circ.132.suppl_3.19447 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Sara Hussain ◽

Osman Al-Radi ◽

Prisca Pondorfer ◽

Lars Grosse-Wortmann ◽

Luc Mertens ◽

...

Keyword(s):

Right Ventricular ◽

Pulmonary Valve Replacement ◽

Least Square ◽

Practical Reasons ◽

Ordinary Least Square ◽

End Diastolic Volume ◽

Risk Patients ◽

The Relationship

Introduction: Right Ventricular End-Diastolic Volume indexed (RVEDVi) obtained by MRI is an accurate measure of RV size and a marker for secondary complications. Echo RV measurements are used early in life after TOF repair for practical reasons. We sought to examine the correlation between early echo Right Ventricular End-Diastolic Dimension z-score (RVEDDz) and MRI RVEDVi at 15 years post-repair. The relationship between these parameters and repair technique is investigated. Methods: 185 TOF patients were repaired at our institution from 1996-2002. Repair techniques were: annulus preservation (AP=124), trans-annular patch (TAP=56), and Pulmonary valve replacement (n=5, patients excluded). Data was reviewed for outcomes, echo studies, and MRI reports. A linear ordinary least square model demonstrated the relationship between early RVEDDz and late RVEDVi (n=57) . Longitudinal analysis with mixed effects model was performed on 783 serial echocardiograms (n=146) to demonstrate the effect of technique on RVEDDz progression. Results: RVEDDz at 1-5 years post-repair was a significant predicator for late RVEDVi (p=0.0016). A change in RVEDDz from 0-3 predicted an increase in RVEDVi of 28 mL. TAP repair was an independent predictor of a larger RVEDVi (p=0.0011). TAP was associated with more RV dilation throughout follow-up (0.37 RVEDDz higher every 5 years, p<0.0001). TAP patients had larger late RV volumes for the same early RVEDDz as those with AP repair (Fig. 1). The same findings were demonstrated in a sub-analysis of anatomically matched patients who could have had either TAP or AP based on surgeon choice. Conclusion: These results from a single institution support the use of RVEDDz by echo as an early maker for late MRI RV volumes in TOF. Early identification of high risk patients may influence decisions around follow-up and re-interventions. Larger population studies are needed to confirm these findings and the effects of technique on long-term RV health. Fig 1.

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Lung Function in Old Age and Physical Activity From Midlife to Old Age: Longitudinal Study With 24-30 Years' Follow-Up

Innovation in Aging ◽

10.1093/geroni/igab046.1764 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 457-457

Author(s):

Ingemar Kåreholt ◽

Liberta Mehmedi ◽

Charlotta Nilsen

Keyword(s):

Physical Activity ◽

Lung Function ◽

Old Age ◽

Healthy Aging ◽

Oldest Old ◽

Panel Study ◽

Older Age ◽

The Relationship ◽

Late Midlife

Abstract The study investigated the role of physical activity, from midlife to older age, in relation to lung function in older age. In order to increase the understanding of the relationship between physical activity and lung function, the relationship between physical activity in midlife and physical activity in older age was also studied. Two Swedish studies based on nationally representative samples were used in this study, the Level of Living Survey, LNU, and the Swedish Panel Study of Living Conditions of the Oldest Old, SWEOLD. The participants were interviewed on three occasions; at the mean ages of 53 years, 61 years, and 81 years. The average follow-up time from the last to the first interview was 24-30 years. The results show that more physical activity in late midlife (mean age of 61 years) was associated with better lung function in older age. The association persists but attenuates when physical activity in older age was included in the analyses. There was also a strong association between physical activity in older age and better lung function in older age. Physical activity in late midlife had a positive association with physical activity in older age. This study shows the importance of physical activity in late midlife and in older ages to maintain good lung function in older ages. To invest in preventive actions in the form of physical activity are vital to be able to promote healthy aging, and should include the oldest old (76+).

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Exercise intolerance in obese children and adolescents

Asian Biomedicine ◽

10.5372/1905-7415.0805.341 ◽

2014 ◽

Vol 8 (5) ◽

pp. 659-664

Author(s):

Kanokpan Ruangnapa ◽

Suchada Sritippayawan ◽

Sompol Sanguanrungsirikul ◽

Jitladda Deerojanawong ◽

Nuanchan Prapphal

Keyword(s):

Lung Function ◽

Children And Adolescents ◽

Cardiopulmonary Exercise Test ◽

Exercise Intolerance ◽

Z Score ◽

Obese Children ◽

Cardiopulmonary Exercise ◽

Ventilatory Equivalent ◽

Lung Functions

Abstract Background: Abnormal lung function has been reported in the obese population and is associated with the severity of obesity. Objectives: To identify abnormal lung function in obese children and adolescents, and examine the cardiopulmonary response of those who have abnormal lung functions during exercise, and to reveal predictors of exercise intolerance in this population. Methods: Fifty obese participants aged 8–18 years (56% male; mean age 13.2 ± 2.0 years; mean BMI 33.0 ± 3.6 kg/m2, mean BMI z score 3.1 ± 0.3) underwent spirometry, lung volume evaluation, and a cardiopulmonary exercise test. Results: Lung function abnormalities and exercise intolerance because of pulmonary limitations were found in 36% and 74% of the participants, respectively. A comparison of participants with normal and abnormal lung functions revealed a lower breathing reserve and a higher ventilatory equivalent for CO2 production (VE/VCO2) during exercise in those who had lung function abnormalities (18 ± 15 vs 30±10%, P <0.001 and 30.3 ± 3.3 vs 29.6 ± 3.1; P = 0.02, respectively). Exercise intolerant participants had a higher BMI z score compared with those who were not (3.1 ± 0.3 vs 2.9 ± 0.3; P = 0.03). BMI z score ≥ 2.84 had an 80% sensitivity and 67% specificity for predicting exercise intolerance in this population. Conclusions: Evaluations of lung function and exercise capacity should be included in the follow-up planning for obese children and adolescents. A BMI z score ≥ 2.84 was most sensitive for predicting exercise intolerance in this population.

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Are elevated plasma fibrinogen associated with lung function? An 8-year follow-up of the ELSA study

PLoS ONE ◽

10.1371/journal.pone.0259498 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0259498

Author(s):

Camila Thais Adam ◽

Ione Jayce Ceola Schneider ◽

Danielle Soares Rocha Vieira ◽

Tauana Prestes Schmidt ◽

Fernando Cesar Wehrmeister ◽

...

Keyword(s):

Older Adults ◽

Lung Function ◽

Plasma Fibrinogen ◽

Elevated Plasma ◽

Lung Function Decline ◽

Function Impairment ◽

The Relationship ◽

Lung Function Impairment ◽

English Longitudinal Study

Background Fibrinogen is an important biomarker of inflammation, but findings from longitudinal studies that correlated fibrinogen with lung function in older adults are inconsistent. Aim To investigate the relationship between fibrinogen plasma levels and lung function impairment later in life. Methods Longitudinal analysis of 2,150 participants of the English Longitudinal Study of Ageing (ELSA) aged 50 years and older. Associations between changes in plasma fibrinogen between waves 2 (2004–05) and 4 (2008–09) and lung function in wave 6 (2012–13) were performed using multiple linear regression adjusted by potential confounders. Results Regarding the fibrinogen profile, 18.5% of the participants presented higher levels in both waves. In the adjusted models, the maintenance of high fibrinogen levels was associated with a significant reduction of lung function only for men. FEV1 showed a reduction of 0.17L, FVC of 0.22L, and the percentages predicted were 5.16% for FEV1 and 6.21% for FVC compared to those that maintained normal levels of fibrinogen. Discussion To the best of our knowledge, this was the first study investigating the relationship between changes in fibrinogen levels over a long follow-up period and lung function in older adults without pre-existing chronic diseases. ELSA has information on critical demographic and clinical parameters, which allowed to adjust for potential confounding factors. Conclusion It was found that the persistence of high levels of plasma fibrinogen in older English men, but not women, is associated with lung function decline. Therefore, plasma fibrinogen showed to be an important biomarker of pulmonary dysfunction in this population.

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Frequency-dependent left ventricular performance in women and men

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01125.2011 ◽

2012 ◽

Vol 302 (11) ◽

pp. H2363-H2371 ◽

Cited By ~ 10

Author(s):

Rodrigo V. Wainstein ◽

Zion Sasson ◽

Susanna Mak

Keyword(s):

Mechanical Performance ◽

Left Ventricular ◽

Right Atrial ◽

Stroke Work ◽

Ventricular Performance ◽

End Diastolic Volume ◽

Specific Manner ◽

And Function ◽

Inotropic Responses ◽

The Relationship

We aimed to determine whether sex differences in humans extend to the dynamic response of the left ventricular (LV) chamber to changes in heart rate (HR). Several observations suggest sex influences LV structure and function in health; moreover, this physiology is also affected in a sex-specific manner by aging. Eight postmenopausal women and eight similarly aged men underwent a cardiac catheterization-based study for force-interval relationships of the LV. HR was controlled by right atrial (RA) pacing, and LV +dP/d tmax and volume were assessed by micromanometer-tipped catheter and Doppler echocardiography, respectively. Analysis of approximated LV pressure-volume relationships was performed using a time-varying model of elastance. External stroke work was also calculated. The relationship between HR and LV +dP/d tmax was expressed as LV +dP/d tmax = b + mHR. The slope ( m) of the relationship was steeper in women compared with men (11.8 ± 4.0 vs. 6.1 ± 4.1 mmHg·s−1·beats−1·min−1, P = 0.01). The greater increase in contractility in women was reproducibly observed after normalizing LV +dP/d tmax to LV end-diastolic volume (LVVed) or by measuring end-systolic elastance. LVVed and stroke volume decreased more in women. Thus, despite greater increases in contractility, HR was associated with a lesser rise in cardiac output and a steeper fall in external stroke work in women. Compared with men, women exhibit greater inotropic responses to incremental RA pacing, which occurs at the same time as a steeper decline in external stroke work. In older adults, we observed sexual dimorphism in determinants of LV mechanical performance.

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Royal Naval Dockyards Asbestosis Research Project: Nine-Year follow-up Study of Men Exposed to Asbestos in Devonport Dockyard

Journal of the Royal Society of Medicine ◽

10.1177/014107688007300507 ◽

1980 ◽

Vol 73 (5) ◽

pp. 337-344 ◽

Cited By ~ 10

Author(s):

C E Rossiter ◽

J R Heath ◽

P G Harries

Keyword(s):

Lung Function ◽

Vital Capacity ◽

Forced Expiratory Volume ◽

Dust Exposure ◽

Progression Of Disease ◽

Asbestos Related Disease ◽

Almost All ◽

Parenchymal Abnormalities ◽

Restrictive Pattern

Progression of asbestos-related disease was assessed in a group of 253 dockyard workers examined in 1966 and 1975. Despite the almost complete protection from exposure to asbestos since 1966, radiographic parenchymal abnormalities increased and occurred more frequently during the next 9 years in those men who had been more heavily exposed to asbestos. Lung function values were lower in those most heavily exposed and were declining at a faster rate than in those with less dust exposure. The most sensitive lung function index was the transfer factor. Those men with persistent crackles in 1966 exhibited a restrictive pattern of lung function, whereas an obstructive pattern was seen in men with wheezes in 1966. The men with irregular small opacities of category 1/1 or more or with diffuse pleural change in 1966 and who survived to 1975 had worse lung functions than any other groups. Progression of disease was greater for smokers than non-smokers, with those who gave up smoking between 1966 and 1975 suffering the greatest changes. This latter group showed most increase in small opacities and included almost all new cases of diffuse pleural changes. They also showed the greatest declines in forced expiratory volume and forced vital capacity.

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