Effort Intolerance Research Articles

Prevalence and symptoms of Long Covid-19 in the workplace.

The symptoms of Long coronavirus disease 2019 (Covid-19) are heterogeneous, creating uncertainty for employers regarding the diagnosis. The prevalence of Long Covid-19 in the workforce is also unknown. Furthermore, workers affected by Long Covid-19 encounter considerable difficulties in ensuring work safety and returning to their jobs due to this condition. This review is aimed to identify the prevalence of Long Covid-19 in the workplace and to determine the various symptoms of Long Covid-19 experienced by the workers. A meta-analysis was conducted to calculate the pooled estimates for the prevalence of Long Covid-19. Heterogeneity among the estimates was evaluated using the I² statistic. The pooled prevalence of Long Covid-19 among workers across the 11 studies was 38% (95% CI 23-56). A total of 43 symptoms associated with Long Covid-19 were identified in the workplace, with the top five symptoms being dyspnoea at moderate activity (51%, 95% CI 39-62), mental symptoms (38%, 95% CI 6-87), dyspnoea at mild activity (35%, 95% CI 25-47), fatigue (26%, 95% CI 3-78) and effort intolerance (24%, 95% CI 15-35). The review indicates a significant burden of long-lasting symptoms within the workforce. The top five reported symptoms of Long Covid-19 weredyspnoea during mild and moderate activities, mental symptoms, fatigue and effort intolerance.

Associations of iron deficiency with cardiac function, congestion, exercise capacity and prognosis in heart failure.

Uncertainty exists about defining true iron deficiency (ID) in heart failure (HF) patients. We assessed the relationship of different ID definitions with cardiac structure and function, congestion, exercise capacity, and prognosis in HF outpatients. Iron deficiency was defined according to guidelines (G-ID: ferritin <100 ng/ml or ferritin 100-299 ng/ml with transferrin saturation [TSAT] <20%). Alternative ID definitions based on TSAT (<20%), iron (≤13 μmol/L), and ferritin (<100 or < 300 ng/ml) were explored. Relationships with rest/exercise measures of cardiac function and congestion using ultrasound, effort intolerance and adverse outcome (HF hospitalizations or all-cause mortality) were assessed. Of 1502 patients (72% with left ventricular ejection fraction [LVEF] ≥50%), 471 (31%) had TSAT <20%, while 728 (48%) had G-ID. Patients with TSAT <20% or G-ID had greater left atrial volume but similar LVEF. Lower TSAT, iron and haemoglobin, but not ferritin, were associated with more signs of congestion by ultrasound. After correcting for multiple clinical variables, including haemoglobin, TSAT was directly associated with peak oxygen uptake (standardized coefficient 0.069, p = 0.041), while ferritin was not. There was no interaction with HF phenotype (HF with preserved vs. reduced LVEF). During a median follow-up of 18 months, TSAT <20% and iron ≤13 μmol/L were associated with worse outcomes in models adjusted for clinical variables, including LVEF and N-terminal pro-B-type natriuretic peptide (hazard ratio 2.48, 95% confidence interval 1.88-3.17 and 1.93, 1.48-2.52, respectively), while G-ID or ferritin <100 or <300 ng/ml were not. In HF outpatients, TSAT <20% is more consistently associated with congestion by ultrasound and poorer functional capacity than other ID definitions, irrespective of LVEF. TSAT <20% and iron ≤13 μmol/L, but not G-ID or ferritin-based ID, predict a worse prognosis in HF outpatients with preserved and reduced LVEF.

Changes in peak oxygen consumption on excercise and cardiomyopathy disease stage in Fabry disease

Abstract Background Fabry disease (FD) is an X-linked lysosomal storage disorder manifesting as deficiency in the enzyme α-Galactosidase A (1) resulting in multi-organ accumulation of globotriaosylceramide (Gb3) (2) This causes predominantly cardiac, renal and cerebrovascular manifestations. Shortness of breath and exercise intolerance are common and can be related to multiple underlying mechanisms. Cardiopulmonary exercise testing (CPEX) quantifies aerobic fitness, functional capacity, chronotropic and haemodynamic response to exercise, and attributes effort intolerance to different aetiologies, including impaired cardiac and respiratory function. Purpose We hypothesise that there is progressive effort intolerance that reflects continual cardiac Gb3 accumulation, becoming common during myocardial hypertrophy and disabling in the fibrosis and inflammation stage. The aims of this study were to ascertain frequency and severity of exercise intolerance in FD by investigating the relationship between peak maximal oxygen uptake (VO2 max) and cardiac disease stage, quantified based on a four-point scale, as proposed in published literature (3). Methods This was a retrospective review of adults with FD and exercise intolerance attending a specialist clinic who had undergone either CPEX or six-minute walk testing (6MWT) in those less mobile. Biochemical, cardiac magnetic resonance (CMR) imaging and transthoracic echocardiographic (TTE) data were also collected. Results N=54 patients underwent CPEX and N=35 patient underwent 6MWT. Estimated peak VO2 max was calculated using 6MWD in those undergoing 6MWT. Median age was 54 (IQR 40-62) years and 53% were male. Patients were equally distributed across disease stage (1-4). There were significant trends in age (increasing) and gender (male predominance) from stage 1-4. Age/sex-normalised peak VO2 max values were calculated as per published literature due to the confounding effect of age and male gender. Mean normalised VO2 max was 35.5ml/kg/min for the cohort, an underperformance of 12.3 ± 8.0 ml/kg/min. The magnitude of underperformance began from stage 1 (no cardiomyopathy) and increased with each stage (Figure 1). Impairments in renal (creatinine and albumin: creatinine ratio) and cardiac biomarkers (troponin and N-terminal pro brain natriuretic peptide) was associated with reduced VO2 max (Table 1). Increased indexed left ventricular mass on CMR and impairments in atrial volume and function on TTE were also associated with a reduction in VO2 max (Table 1). Conclusion This study is the first of its kind to demonstrate impairments in peak aerobic capacity in adults with FD and no cardiomyopathy (stage 1) which impairs further with cardiac disease stage. Future work should focus on how disease-modifying therapy can target this using VO2 as an endpoint and marker of response.Normalised peak VO2 max + disease stageVO2 max and blood / imaging parameters

Associations of different definitions of iron deficiency with cardiac structure and function, congestion, exercise capacity and prognosis in heart failure

Abstract Background It is uncertain how best to diagnose iron deficiency (ID) in patients with heart failure (HF) as different ID definitions have been proposed with discordant results. Objectives To assess the relationship of different ID definitions with cardiac structure and function, congestion, exercise capacity, and prognosis in outpatients with HF. Methods ID was defined according to guidelines (G-ID: ferritin &amp;lt;100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation [TSAT] &amp;lt;20%) or as TSAT &amp;lt;20%. Alternative definitions (iron &amp;lt;13 ¼mol/L, ferritin &amp;lt;100 and &amp;lt;300 ng/mL) were explored. Relationship with rest and exercise ultrasound findings, cardiopulmonary exercise testing and a composite endpoint of cardiovascular hospitalisations or all-cause mortality were assessed. Results Of 1502 patients (72% with left ventricular ejection fraction [LVEF] ≥50%), 471 (31%) had TSAT &amp;lt;20%, while 728 (48%) had G-ID. Compared to those without ID, patients with TSAT &amp;lt;20% or G-ID showed impaired cardiac structure and function at rest and peak exercise and lower peak oxygen consumption; they were also more likely to display a discontinuous renal venous flow pattern and more lung B-lines. Only TSAT &amp;lt;20% was associated with significant inferior vena cava dilatation. Lower TSAT, iron and haemoglobin were associated with more severe effort intolerance and ultrasound signs of congestion, while ferritin and LVEF were not (Picture 1). During a median follow-up of 16 months, 62 (4%) patients died, and 244 (16%) were hospitalised for cardiovascular reasons. No patients were hospitalised immediately after the enrolment visit because of clinical findings. At Kaplan-Meier analyses, TSAT &amp;lt;20% was associated with a greater risk of adverse events, as were iron ≤13 ¼mol/L, ferritin ≥300 ng/mL and &amp;lt;100 ng/mL (p &amp;lt;0.01 vs ferritin 100-299 ng/mL) and G-ID (Picture 2). After adjusting for age, sex, diabetes, haemoglobin, estimated glomerular filtration rate (eGFR), NT-proBNP, rest LVEF and peak VO2 &amp;lt;16 mL/kg/min, TSAT &amp;lt;20% and iron ≤13 ¼mol/L were associated with worse outcomes (hazard ratio 2.41, 95% confidence interval 1.85-3.14 and 1.90, 1.46-2.47), while G-ID or ferritin &amp;lt;100 or &amp;lt;300 ng/mL were not (Picture 1). Conclusions In outpatients with HF, TSAT &amp;lt;20% is more consistently associated with echocardiographic signs of poorer functional capacity and multi-organ congestion than other ID definitions. TSAT &amp;lt;20% and iron ≤13 ¼mol/L, but not G-ID or ferritin-based ID, seem to predict a worse prognosis.Picture 1Picture 2

Traditional cardiovascular risk factors and coronary microvascular disease in women and men- a single center study

Abstract Introduction Coronary microvascular dysfunction (CMD) is a common, often missed, cause for effort intolerance and angina symptoms, and is associated with adverse clinical outcomes. Risk factors for the development of CMD have not been fully elucidated, and studies examining sex associated differences in traditional cardiovascular risk factors (TCRs) for obstructive coronary artery disease (CAD) in patients with CMD have yielded conflicting results. Although several non-invasive methods for the evaluation of CMD exist, currently, catheter-based invasive assessment is the gold standard for the diagnosis of coronary microvascular dysfunction. Purpose To examine the association between TCR and CMD and sex associated differences in TCR, in a prospective cohort of patients undergoing invasive microvascular function evaluation in a large tertiary medical center. Methods In this single center, prospective registry, we enrolled patients with non-obstructive CAD undergoing clinically indicated invasive assessment of coronary microvascular function between November 2019 and March 2023. Measurements of microvascular function included CFR, IMR, RRR as well as FFR. Pathologic CFR was defined as &amp;lt;2.5 or &amp;lt;2. Associations between coronary microvascular dysfunction, traditional cardiovascular risk factors, and sex were assessed using univariate and multivariate regression models. Results Overall, 245 patients with non-obstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range [IQR]: 59,75). Microvascular dysfunction was diagnosed in 141 patients (57.5%). The prevalence of microvascular dysfunction was similar in women and men in the entire cohort (59.0% vs. 57.0%; p=0.77). In 41 patients diagnosed with functional microvascular dysfunction there were more women than men (70.7% vs. 29%). When using a threshold of CFR&amp;lt;2.5 no association was found between traditional risk factors for coronary atherosclerosis and CMD regardless of whether CMD was structural or functional. In women, but not in men, older age and the presence of previous ischemic heart disease were associated with lower coronary flow reserve (CFR) (β=-0.29; p&amp;lt;0.01 and β=-0.15; p=0.05, respectively) and lower resistive reserve ratio (RRR) (β=-0.28; p&amp;lt;0.01 and β=-0.17; p=0.04, respectively). When using a threshold of &amp;lt;2.0 for CFR similar results were found. Conclusion The prevalence of TCRs was similar in patients with and without CMD. In women, older age and previous IHD were associated with lower CFR and RRR values while no association between TCRs and indices of CMD was found in men. It is likely that there are other, currently unknown risk factors for CMD as well as unique risk factors for each of its endotypes, beyond TCRs. It is unclear which parameter of microvascular dysfunction is the most accurate, and whether different parameters should be used in women and men. Large-scale multi-center studies to further evaluate these issues are needed.Variables associated with CMDStudy inclusion process

Metoprolol therapy in patients with Eisenmenger syndrome (MINES) study. A single-centre, double-blinded, randomised, placebo-controlled trial

Abstract Background Prevalence of Eisenmenger syndrome is still common in developing countries where early neonatal screening and referral for surgery is seldom possible. Limited number of drugs are available for treatment of this condition. Beta-blockers may improve functional status in these patients. Observational study has shown beta blockers to be safe and effective in improving effort intolerance in patients with Eisenmenger syndrome. Purpose To study the safety and efficacy of metoprolol succinate therapy in patients with Eisenmenger syndrome. Methods In this double-blind, placebo-controlled study, we randomly assigned 60 patients with Eisenmenger syndrome to receive placebo or to receive 25 mg of metoprolol succinate once daily for 2 weeks followed by 25 mg twice daily for 14 weeks (total of 16 weeks). The primary outcome was mean difference in 6-minute walk test (6MWT) distance. Secondary outcomes were clinical composite outcome (all-cause death, heart failure hospitalization, worsening of heart failure, change in WHO functional class, and new onset syncope), change in resting saturation, Tricuspid Annular Plane Systolic Excursion (TAPSE) and NT Pro BNP level at 16 weeks. Results At 16 weeks, the mean difference in 6MWT distance between treatment group and placebo group as per protocol analysis was 6 meters (95% confidence interval, - 7.43 to 19.49; P 0.37), and the mean difference in 6MWT distance as per intention to treat analysis was -1.1 meters (95% confidence interval, - 16.97 to 14.77; P 0.89). Clinical composite outcome occurred more in the treatment group 5(17%) as compared to the placebo group 1(3%) (P 0.197) though it did not reach statistical significance. This was primarily driven by worsening of heart failure in the treatment group. Compared to baseline metoprolol group had 37% increase in NT pro BNP level while placebo group had 13% (-313.69, 88.80) reduction in NT Pro BNP level. There was no difference in TAPSE 0.05 (95% confidence interval -0.62 to 0.72; P 0.88) or resting saturation -0.06 (95% confidence interval -0.88 to 0.75; P 0.87) between the two groups at 16 weeks Conclusion Metoprolol succinate therapy did not improve 6-minute walk distance at 16 weeks among patients with Eisenmenger syndrome compared to placebo. Metoprolol succinate therapy was associated with increased clinical composite outcomes, primarily driven by worsening of heart failure.Graphic Abstract of MINES study

CA125 outperforms NT-proBNP in the prediction of maximum aerobic capacity in heart failure with preserved ejection fraction and kidney dysfunction.

Heart failure with preserved ejection fraction (HFpEF) often coexists with chronic kidney disease (CKD). Exercise intolerance is a major determinant of quality of life and morbidity in both scenarios. We aimed to evaluate the associations between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) with maximal aerobic capacity (peak VO2) in ambulatory HFpEF and whether these associations were influenced by kidney function. This single-centre study prospectively enrolled 133 patients with HFpEF who performed maximal cardiopulmonary exercise testing. Patients were stratified across estimated glomerular filtration rate (eGFR) categories (<60ml/min/1.73m2 versus ≥60ml/min/1.73m2). The mean age of the sample was 73.2±10.5years and 56.4% were female. The median of peak VO2 was 11.0ml/kg/min (interquartile range 9.0-13.0). A total of 67 (50.4%) patients had an eGFR <60ml/min/1.73m2. Those patients had higher levels of NT-proBNP and lower peak VO2, without differences in CA125. In the whole sample, NT-proBNP and CA125 were inversely correlated with peak VO2 (r=-0.43, P<.001 and r=-0.22, P=.010, respectively). After multivariate analysis, we found a differential association between NT-proBNP and peak VO2 across eGFR strata (P for interaction=.045). In patients with an eGFR ≥60ml/min/1.73m2, higher NT-proBNP identified patients with poorer maximal functional capacity. In individuals with eGFR <60ml/min/1.73m2, NT-proBNP was not significantly associated with peak VO2 [β=0.02 (95% confidence interval -0.19-0.23), P=.834]. Higher CA125 was linear and significantly associated with worse functional capacity without evidence of heterogeneity across eGFR strata (P for interaction=.620). In patients with stable HFpEF, NT-proBNP was not associated with maximal functional capacity when CKD was present. CA125 emerged as a useful biomarker for estimating effort intolerance in HFpEF irrespective of the presence of CKD.

Home-based exercise program for people with residual disability following hospitalization for COVID-19: Randomized control trial

BackgroundThe best exercise program for individuals with effort intolerance or hypoxia at rest and/or during exercise post-COVID-19 treatment who have already had in-hospital rehabilitation remains unknown. ObjectiveWe evaluated the efficacy of a home-based rehabilitation exercise program intervention that included teleconsultations with a specialist nurse. MethodsThis was a multicenter randomized controlled trial for individuals who had been diagnosed with, and treated for, COVID-19. Despite inpatient rehabilitation they still had effort intolerance; this was defined as being a) only able to walk <70 % of the predicted distance during the six-minute walking test (6MWT) and/or b) oxygen desaturation all day long/during effort. The primary outcome was effort tolerance, as evaluated by the 6MWT. Secondary outcomes were dyspnea, fatigue, spirometry, respiratory muscle evaluations, and oxygenation. The Intervention group performed 4 weeks of a self-directed exercise program with bi-weekly physiotherapist video calls; the Control group participated in physical activity howsoever they wished. Exercises were divided into 4 intensity levels according to disability and oxygen desaturation. The program progressively increased from low (walking, free-body exercise, sit-to-stand, and balance exercises) to high (speed walking with a pedometer, cycle ergometer, and strengthening exercises). ResultsWe included 79 participants: 40 in the Intervention and 39 in the Control group. Mean (SD) age was 67.1 (10.3) years; 72 % (n = 57) were male. No intergroup differences in effort tolerance were found [Intervention 77.6 (75.4)m vs Control 49.5 (73.3)m (p = 0.109)]. Participants with 6MWT distance results < lower limit of normality values showed best improvements in mean (SD) effort tolerance: Intervention, 120.1 (75.8)m vs Control, 59.1 (75.6)m (p = 0.035). After 2 months, mean (SD) 6MWT distances in the 2 groups were similar: Intervention, 475.9 (82.4)m vs Control, 469.2 (118.9)m (p = 0.807). ConclusionsIn individuals with residual disability post-COVID-19 and after inpatient rehabilitation, a home-based exercise program with teleconsultation significantly improves effort tolerance but only for people who had severe effort intolerance at baseline. Database registrationClinicalTrials.gov number, NCT04821934

Acute and chronic effects of levosimendan in the ZSF1 obese rat model of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a syndrome characterized by impaired cardiovascular reserve in which therapeutic options are scarce. Our aim was to evaluate the inodilator levosimendan in the ZSF1 obese rat model of HFpEF. Twenty-week-old male Wistar-Kyoto (WKY), ZSF1 lean (ZSF1 Ln) and ZSF1 obese rats chronically treated for 6-weeks with either levosimendan (1 mg/kg/day, ZSF1 Ob + Levo) or vehicle (ZSF1 Ob + Veh) underwent peak-effort testing, pressure-volume (PV) haemodynamic evaluation and echocardiography (n = 7 each). Samples were collected for histology and western blotting. In obese rats, skinned and intact left ventricular (LV) cardiomyocytes underwent in vitro functional evaluation. Seven additional ZSF1 obese rats underwent PV evaluation to assess acute levosimendan effects (10 μg/kg + 0.1 μg/kg/min). ZSF1 Ob + Veh presented all hallmarks of HFpEF, namely effort intolerance, elevated end-diastolic pressures and reduced diastolic compliance as well as increased LV mass and left atrial area, cardiomyocyte hypertrophy and increased interstitial fibrosis. Levosimendan decreased systemic arterial pressures, raised cardiac index, and enhanced LV relaxation and diastolic compliance in both acute and chronic experiments. ZSF1 Ob + Levo showed pronounced attenuation of hypertrophy and interstitial fibrosis alongside increased effort tolerance (endured workload raised 38 %) and maximum O2 consumption. Skinned cardiomyocytes from ZSF 1 Ob + Levo showed a downward shift in sarcomere length-passive tension relationship and intact cardiomyocytes showed decreased diastolic Ca2+ levels and enhanced Ca2+ sensitivity. On molecular grounds, levosimendan enhanced phosphorylation of phospholamban and mammalian target of rapamycin. The observed effects encourage future clinical trials with levosimendan in a broad population of HFpEF patients.

Clinical Evaluation of Dyspnoea in Obstructive Lung Disease – Progressing from Psychometrics to Physiology

Dyspnoea is a common symptom that afflicts persons with myriad medical conditions. Among sufferers of lung disorders such as chronic obstructive pulmonary disease, dyspnoea, together with effort intolerance, are the major complaints. Dyspnoea is a marker of disease severity and adverse prognosis of chronic obstructive pulmonary disease, and the need for symptom alleviation in improving health status is ever-present, but the quantification of this symptom is challenging in clinical practice, and is mostly limited to the use of questionnaires and self-reports currently. Numerous psychometric tools have been developed to measure the severity of dyspnoea clinically, but their utility is vitiated by the complexity and multidimensional nature of the symptom. The lack of a universally accepted and accurate measurement tool is likely to hinder future progress in developing novel treatments for relieving dyspnoea. Physiological measurements have been used to complement or supplant psychometric evaluation of dyspnoea but simple stationary lung function tests do not correlate sufficiently well with dyspnoea severity in patients with chronic obstructive pulmonary disease, while complex exercise testing is impractical or limited to specialized research labs. In recent years, the use of non-invasive surface electromyography of the diaphragm and/or accessory muscles of respiration is gaining attention as a promising physiological assessment of dyspnoea with potential for widespread clinical applications. Although substantial technological gaps still exist between bench and bedside, the current interest, as evidenced by the number of med-tech collaborations in surface respiratory electromyography, appears to be well justified. This review aims to summarize the past and present methodologies as well as future developments in evaluating and quantifying dyspnoea, especially in patients with chronic obstructive pulmonary disease.

Distinct effects of type 2 diabetes and obesity on cardiopulmonary performance.

Effort intolerance is frequent in patients with overweight/obesity and/or type 2 diabetes (T2D) free from cardiac and respiratory disease. We sought to quantify the independent effects of T2D and body mass index (BMI) on cardiopulmonary capacity and gain insights on the possible pathophysiology by case-control and regression analyses. Patients at high/moderate cardiovascular risk, with or without T2D, underwent spirometry and combined echocardiography-cardiopulmonary exercise test as part of their clinical workup. Subjects with evidence of cardiopulmonary disease were excluded. The effects of T2D and obesity were estimated by multivariable models accounting for known/potential confounders and the major pathophysiological determinants of oxygen uptake at peak exercise (VO2peak ) normalized for fat-free mass (FFM). In total, 109 patients with T2D and 97 controls were included in the analysis. The two groups had similar demographic and anthropometric characteristics except for higher BMI in T2D (28.6 ± 4.6 vs. 26.3 ± 4.4 kg/m2 , p = .0003) but comparable FFM. Patients with T2D achieved lower VO2peak than controls (18.5 ± 4.4 vs. 21.7 ± 8.3 ml/min/kg, p = .0006). Subclinical cardiovascular dysfunctions were observed in T2D: concentric left ventricular remodelling, autonomic dysfunction, systolic dysfunction and reduced systolic reserve. After accounting for confounders and major determinants of VO2peakFFM , T2D still displayed reduced VO2peak by 1.0 (-1.7/-0.3) ml/min/kgFFM , p = .0089, while the effect of BMI [-0.2 (-0.3/0.1) ml/min/kgFFM , p = .06 per unit increase], was largely explained by a combination of chronotropic incompetence, reduced peripheral oxygen extraction, impaired systolic reserve and ventilatory (in)efficiency. T2D is an independent negative determinant of VO2peak whose effect is additive to other pathophysiological determinants of oxygen uptake, including BMI.

Left Atrial Stiffness Index as a Predictor of Effort Intolerance and Hemodynamics Evaluated by Invasive Exercise Stress Testing in Degenerative Mitral Regurgitation

In patients with degenerative mitral regurgitation (DMR), peak oxygen consumption is the significant prognostic factor, and exercise intolerance has been considered a trigger for surgical intervention. The significant mitral regurgitation (MR) induces left atrial (LA) remodeling, but the significance of LA stiffness calculated by the ratio of E/e' to LA reservoir strain in degenerative MR has not been elucidated. A total of 30 patients with asymptomatic or minimally symptomatic grade ≥III+DMR underwent the cardiopulmonary exercising test simultaneously with invasive hemodynamic assessment. LA stiffness index significantly correlated with exercise hemodynamic deterioration, including pulmonary arterial wedge pressure (r=0.71, p <0.01), systolic pulmonary arterial pressure at peak exercise (r=0.73, p <0.01), and pulmonary circulatory reserve (mean pulmonary arterial pressure/cardiac output slope, r=0.45, p=0.012). Multiple linear regression analysis revealed that the higher LA stiffness index was significantly associated with decreased percent predicted peak oxygen consumption (per 0.1 increase, β -4.0, 95% confidence interval -6.9 to -1.3, p <0.01) independently of MR deterioration during exercise. In conclusion, increased LA stiffness was associated with exercise intolerance through hemodynamic deterioration during exercise in patients with asymptomatic or minimally symptomatic severe DMR.

The Mechanism of Effort Intolerance in Patients with Peripheral Arterial Disease: A Combined Stress Echocardiography and Cardiopulmonary Exercise Test.

We used a combined stress echocardiography and cardiopulmonary exercise test (CPET) to explore effort intolerance in peripheral arterial disease (PAD) patients. Twenty-three patients who had both PAD and coronary artery disease (CAD) were compared with twenty-four sex- and age-matched CAD patients and fifteen normal controls using a symptom-limited ramp bicycle CPET on a tilting dedicated ergometer. Echocardiographic images were obtained concurrently with gas exchange measurements along predefined stages of exercise. Oxygen extraction was calculated using the Fick equation at each activity level. Along the stages of exercise (unloaded; anaerobic threshold; peak), in PAD + CAD patients compared with CAD or controls, diastolic function worsened (p = 0.051 and p = 0.013, respectively), and oxygen consumption (p < 0.001 and p < 0.001, respectively) and oxygen pulse (p = 0.0024 and p = 0.0027, respectively) were reduced. Notably, oxygen pulse was blunted due to an insufficient increase in both stroke volume (p = 0.025 and p = 0.028, respectively) and peripheral oxygen extraction (p = 0.031 and p = 0.038, respectively). Chronotropic incompetence was more prevalent in PAD patients and persisted after correction for beta-blocker use (62% vs. 42% and 11%, respectively). In PAD patients, exercise limitation is associated with diastolic dysfunction, chronotropic incompetence and peripheral factors.

Parasympathetic autonomic dysfunction is more often evidenced than sympathetic autonomic dysfunction in fluctuating and polymorphic symptoms of "long-COVID" patients

Several disabling symptoms potentially related to dysautonomia have been reported in “long-COVID” patients. Unfortunately, these symptoms are often nonspecific, and autonomic nervous system explorations are rarely performed in these patients. This study aimed to evaluate prospectively a cohort of long-COVID patients presenting severe disabling and non-relapsing symptoms of potential dysautonomia and to identify sensitive tests. Autonomic function was assessed by clinical examination, the Schirmer test; sudomotor evaluation, orthostatic blood pressure (BP) variation, 24-h ambulatory BP monitoring for sympathetic evaluation, and heart rate variation during orthostatism, deep breathing and Valsalva maneuvers for parasympathetic evaluation. Test results were considered abnormal if they reached the lower thresholds defined in publications and in our department. We also compared mean values for autonomic function tests between patients and age-matched controls. Sixteen patients (median age 37 years [31–43 years], 15 women) were included in this study and referred 14.5 months (median) [12.0–16.5 months] after initial infection. Nine had at least one positive SARS-CoV-2 RT-PCR or serology result. Symptoms after SARS-CoV-2 infection were severe, fluctuating and disabling with effort intolerance. Six patients (37.5%) had one or several abnormal test results, affecting the parasympathetic cardiac function in five of them (31%). Mean Valsalva score was significantly lower in patients than in controls. In this cohort of severely disabled long-COVID patients, 37.5% of them had at least one abnormal test result showing a possible contribution of dysautonomia to these nonspecific symptoms. Interestingly, mean values of the Valsalva test were significantly lower in patients than in control subjects, suggesting that normal values thresholds might not be appropriate in this population.

P446 INDEPENDENT EFFECTS OF TYPE 2 DIABETES AND OBESITY ON CARDIOPULMONARY PERFORMANCE IN SUBJECTS AT HIGH CARDIOVASCULAR RISK

Abstract Background Both obesity and type 2 diabetes (T2D) are associated with effort intolerance and heart failure. Since the two conditions often coexist and overlap, their distinct effect on cardiopulmonary performance remains to be elucidated. Methods Patients at high cardiovascular risk, free from any clinical or instrumental evidence of heart disease, with a wide range of body mass index (BMI) values, and with or without T2D underwent combined echocardiography–cardiopulmonary exercise test (eCPET). Patients were divided in T2D and controls, as well as in lean (BMI &amp;lt;25 kg/m2), overweight (BMI 25 – 30 kg/m2), and obese (BMI &amp;gt;30 kg/m2). Results A total of 206 patients was analyzed, divided in 109 patients with T2D and 97 controls. Increased BMI is associated with multiple cardiovascular dysfunctions including chronotropic insufficiency, subclinical systolic dysfunction (reduced global longitudinal strain, GLS), and impaired systolic reserve, achieving significantly lower oxygen uptake and workload. Obesity is associated with reduced lung volumes and mild ventilatory alterations at peak exercise, irrespective of diabetes. T2D patients showed more frequent LV concentric remodeling, worse systolic and diastolic performance at rest with diminished ameliorations during exercise, and worse sympatho–vagal balance as expressed by the higher prevalence of chronotropic insufficiency and delayed heart rate recovery. Nonetheless, when divided in BMI subclasses, the differences between T2D and controls were only evident among lean subjects. In fact, while no difference between T2D and controls was evident among overweight and obese patients, lean individuals with T2D display worse cardiopulmonary performance than lean controls, achieving lower workload and lower VO2peak, revealing systolic dysfunction (lower GLS) and higher LV filling pressures (E/e’). Unlike glycated hemoglobin, strong linear relationships were proven between fat mass and oxygen uptake, workload, systolic, and diastolic indices. Conclusions T2D affects LV dimensions and geometry, systo–diastolic functions, autonomic balance, cardiopulmonary capacity, and exercise tolerance, independently of the presence of obesity. Nonetheless, increased BMI is an even more powerful independent negative determinant of systolic function, autonomic balance, and effort tolerance. These early alterations might partly explain the increased risk of developing heart failure associated with diabetes and obesity.

Left Ventricular Strain in Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome of effort intolerance based on structural and functional abnormalities of the cardiovascular system (CVS). Its prevalence is increasing progressively in comparison to that of heart failure with reduced ejection fraction due to aging, obesity, metabolic stress, and hypertension. Multiple domains of the CVS and peripheral organs have reduced reserve capacity and increased stiffness in patients with HFpEF. This high-gain CVS exhibits increased filling pressures and reduced filling volumes under stress despite the left ventricular ejection fraction, commonly estimated parameter of contractile performance, being normal, i.e., &gt;50%. The cost of increasing cardiac output in terms of left ventricular filling pressures is increased and their relationship shows an upward and more left-directed slope due to reduced ventricular and arterial compliance. At the tissue level, there is myocytic hypertrophy and increased extracellular matrix with capillary rarefaction. There are many phenogroups of HFpEF based on the heart’s ability to secrete natriuretic peptides, degree of dysmetabolism, age, renal function, body fat, rhythm, underlying etiology, and subclinical systolic dysfunction. The left ventricle may be pressure-loaded, volume-loaded, or have equipoise with regard to remodeling. Myocardial performance estimated by parameters other than those based on distance or volume displacement may be abnormal in more than half of the patients underlying the presence of subtle systolic dysfunction. This review looks at myocardial performance and characteristics in HFpEF by deformation imaging using acoustic speckle tracking and its diagnostic and prognostic significance. Research points toward the utility of global longitudinal strain in early detection, biological characterization, and risk stratification of HFpEF. Echocardiographic speckle-tracking-based longitudinal strain analysis represents a method of relatively high value and for sensitive phenotyping of HFpEF which is yet to be utilized optimally. Other dimensions of strain, although extensively studied in HFpEF, do not add much value. The focus is on systolic deformation since there is limited utility of diastolic strain and its rate.

Post COVID-19 cardiac magnetic resonance findings among inpatients vs outpatients

Abstract Background Myocardial injury and myopericarditis constitute an important complication after viral infection. The prevalence of myocardial injury among patients that survived COVID – 19 infections and its causes are still not clear. The purpose of this study is to estimate whether there is a difference in the prevalence of cardiac magnetic findings between patients treated in a hospital vs patients treated at an outpatient clinic. Methods We evaluated 360 cardiac magnetic resonance examinations, performed from 1st of June 2020 until the 31st of August, 2021. Out of them, 141 patients (39%) underwent cardiac magnetic resonance due to persistent symptoms after a SARS-CoV-2 infection. A conventional CMR protocol was performed to rule out myocarditis. Revised 2018 Lake Louise Criteria were used to diagnose myocarditis. All scans were performed by Phillips Medical Systems Ingenia 1.5T. T1 native values were estimated elevated when mapping values measured above 1030ms, T2 mapping values were estimated elevated when greater than 55 ms. Mid wall or subepicardial late gadolinium enhancement, pericardial effusions and extracardiac findings were evaluated. Chi-square test was used. Results Out of 141 patients, 78 patients (55%) had at least one cardiac magnetic resonance finding: either increased T1 (22%), T2 mapping (7%), T2 STIR (1.4%), left gadolinium enhancement (30%), small pericardial effusion (26%) or lung parenchymal changes (12%) after COVID-19. Twenty out of 141 patients (14%) fulfilled the criteria for myocarditis. Out of these 20 patients, 14 patients (70%) received treatment at an outpatient clinic, while 6 patients (30%) were treated from COVID-19 in a hospital (p&amp;lt;0.053). The most prevalent symptoms were effort intolerance and palpitations (50% and 26% respectively). There was no statistical difference in myocarditis prevalence, between hospitalized patients treated with or without corticosteroids (p=0.65), as well as between patients treated with hemodiafiltration (Oxiris filter) and patients without hemodiafiltration (p=0.95). Also, there was no statistical difference between T1 mapping among the inpatients and outpatients (p=0.58), as well as the severity of the clinical picture (p=0.72). There was no statistical difference between the in- and outpatient groups according to age (p=0.46). None of these patients had signs of fulminant myocarditis. Conclusion The prevalence of myopericardial and/or lung involvement after SARS-CoV-2 infection is present in every other cardiac magnetic resonance examination performed for persistent symptoms after a survived COVID-19. Myocarditis after SARS-CoV-2 infection develops regardless of the severity of the symptoms or the treatment method. We can conclude that we have to look for the reasons for myocarditis, beyond the clinical picture and the treatment strategies. Funding Acknowledgement Type of funding sources: None.

Large Fenestrated Atrial Septal Occluder to Treat an Elderly Female in her Seventh Decade

Atrial septal defect (ASD) is one of the common congenital heart anomalies presenting in the geriatric group. It presents with symptoms such as progressive effort intolerance, arrhythmias, and palpitations. Sometimes, associated obstructive and restrictive respiratory diseases can contribute significantly to the symptoms masked by cardiac disease. A female in her seventh decade, presenting with dyspnea, had a large ASD with diastolic dysfunction and moderate pulmonary hypertension. She had persistence of symptoms after initial treatment for cardiac elements. On detailed evaluation, she was found to have mixed obstructive and restrictive respiratory disease. She was treated for respiratory elements under expert pulmonology guidance with significant improvement. The ASD was occluded with a custom-made fenestrated 40 mm LifeTech atrial septal occluder in view of diastolic dysfunction and initial pulmonary arterial hypertension. She remained symptomatically better on her short-term follow-up. The index case highlights the importance of detailed evaluation of elderly patients with large ASDs and individualized care to treat.

Congenitally Corrected Transposition of Great arteries with AV block -cohabitation of structural and electrical cardiac abnormality: a case report

Congenitally Corrected Transposition of Great Arteries (c-TGA) is an anomaly with atrioventricular and ventriculoarterial discordance where left atrium connects to right ventricle and right atrium to left ventricle. However in this case of double inversion, aorta carries saturated blood and pulmonary artery carries venous blood. So, normal physiological circulation is maintained. Our patient, a 38-years-old Bangladeshi male presented with palpitation, dizziness and effort intolerance (NYHAII) during exertion since childhood, which has recently become much worse. However, he had no history of central cyanosis, chest pain or syncope. We diagnosed him as a case of Corrected TGA and second-degree AV block with intermittent complete heart block. A Dual chamber permanent Pacemaker was inserted without any complications. No invasive treatment including corrective surgery was performed because patient’s cardiac function was almost normal. Patient became totally asymptomatic after pacemaker implantation Bangladesh Heart Journal 2022; 37(1): 77-80

Peak atrio-ventricular mechanics predicts exercise tolerance in heart failure patients

PurposeExercise intolerance is a cardinal symptom of patients with heart failure (HF). We hypothesized that patients with HF with preserved ejection fraction (HFpEF) in comparison with those with reduced ejection fraction (HFrEF) have disproportionate exercise-induced impairment of left atrial (LA) function that may explain the effort intolerance. MethodsTotal 40 HFpEF patients, 40 HFrEF patients, and 20 matched healthy controls underwent resting and exercise stress transthoracic echocardiography using modified Bruce protocol with speckle-tracking derived assessments of peak atrial longitudinal strain (PALS) and left ventricular global longitudinal strain (LVGLS). ResultsIn comparison to controls, PALS and LVGLS were reduced in HFpEF and HFrEF patients (P < 0.01); however, the strain magnitudes were significantly lower in HFrEF than in HFpEF (P < 0.01). Both HFpEF and HFrEF showed a 28% and 30% reduction in exercise time in comparison with controls (HFpEF, 363 ± 152, HFrEF 352 ± 91, controls, 505 ± 42 s, P < 0.01) and exercise-related rise in E/E' in HFpEF patients. However, during exercise PALS reduced from resting values by 26% (resting 23.1 ± 4.7 and peak 18.5 ± 3.5, P < 0.01) in HFpEF but only 8% in HFrEF (resting 11.5 ± 1.4 and peak 10.5 ± 1.5, P < 0.01), and remained unchanged in controls (resting 34 ± 1.9 and peak 34.4 ± 1.2, P = 0.4). Regression analysis of the combined data from the HF patients and controls revealed that PALS was independently associated with exercise time such that a 1% reduction in PALS was associated with a 10 s reduction in exercise duration (p < 0.01). PALS at baseline and peak exercise differentiated normal from HF patients. LVGLS at baseline and peak exercise differentiated HFpEF from HFrEF and patients of HFpEF showed abnormality of both PALS and LVGLS. ConclusionAlthough left ventricle and LA strain are lower in HFrEF than HFpEF at rest and exercise compared to healthy controls, patients with HFpEF show more profound deterioration of LA reservoir function with exercise which appears to contribute to exercise intolerance.