Poor Exercise Tolerance Research Articles

Comparative analysis of the 2016 diastolic guidelines and left atrial stiffness in predicting exercise tolerance and cardiac events

Abstract Background While the 2016 ASE/EACVI guideline for diastolic dysfunction is a robust tool for prognostication, their complexity and 20% rate of indeterminate limit their routine clinical practice. Purpose Left atrial (LA) stiffness, calculated as the E/e' ratio divided by LA strain, provides a simpler measure that indirectly reflects LA pressure. This study aims to evaluate whether LA stiffness can be better than the 2016 guidelines in predicting poor exercise tolerance and cardiac events (cardiac death or heart failure hospitalization) in patients with dyspnea. Methods In this retrospective single-center cohort study, 404 patients who underwent echocardiography and cardiopulmonary exercise test simultaneously were reviewed. Poor exercise tolerance was defined by a peak oxygen uptake (VO2) of <14 ml/kg/min or a minute ventilation-carbon dioxide production (VE/VCO2) slope of ≥ 40. The predictive abilities of LA stiffness for peak VO2, VE/VCO2 slope, and cardiac outcomes (cardiac death or heart failure hospitalization) were compared to those of the 2016 guidelines using ROC curve analysis. Results The mean left ventricular ejection fraction was 50% (IQR 58.58-66.70). Of the 404 patients (mean age 58.51, male 50.74%), peak VO2 < 14 and VE/VCO2 ≥ 40 were observed in 38 and 24 patients, and cardiac events occurred in 37 patients during median follow up of 85.45 months. ROC analysis showed that LA stiffness had AUC values of 0.697 (95% CI: 0.604-0.789) for peak VO2 < 14, 0.645 (95% CI: 0.529-0.760) for VE/VCO2 slope ≥ 40, and 0.628 (95% CI: 0.541-0.715) for cardiac events. The 2016 guidelines achieved AUCs of 0.685 (95% CI: 0.604-0.766), 0.586 (95% CI: 0.481-0.690), and 0.589 (95% CI: 0.505-0.674). Statistical comparison revealed no significant difference between the predictive capabilities of LA stiffness and the 2016 guidelines (p-values: 0.735, 0.165, and 0.439, respectively). (Figure) Conclusion LA stiffness offers comparable diagnostic accuracy to the 2016 ASE/EACVI guidelines in assessing poor exercise tolerance and cardiac events in patients with dyspnea. Given its simplicity and ease of measurement, LA stiffness represents a viable alternative for evaluating diastolic dysfunction.ROC curve

Arterial Properties and Ventricular-Arterial Interactions in Severe Aortic Stenosis: Impact on Prognosis.

Systemic arterial properties contribute to clinical heterogeneity and outcomes in degenerative calcific aortic stenosis (AS). Lumped parameters of afterload have previously been associated with adverse left ventricular remodeling, mortality, and poor exercise tolerance in this population, but most studies did not assess pulsatile aortic pressure-flow relations, the gold standard method for assessing arterial load. Moreover, arterial compliance is highly dependent on non-pulsatile (mean) arterial pressure, which influences prognosis in this population. We retrospectively studied 135 patients with severe AS with same-day catheterization and echocardiogram. Invasive aortic pressures and echocardiographic flow waveforms were used to assess pressure-flow and pressure-volume relations using Windkessel modeling and wave separation analyses. We used Cox regression to assess the relationship between pulsatile load and time to death and heart failure hospital admission (DHFA). Total arterial compliance accounting for pressure-dependence (PD-TAC) was independently predictive of all-cause mortality (HR=0.80, 95%CI=0.66-0.97; p=0.023) and DHFA (HR=0.70; 95%CI=0.50-0.97; p=0.031) even after adjustment for age, race, gender, BMI, and comorbidities, while other arterial parameters were not. In patients with severe AS, pressure-dependent arterial compliance predicts adverse outcomes, while traditional pulsatile arterial load measures do not. Our findings suggest that methods accounting for pressure load on the arterial wall are advantageous in this population in which lower mean pressure can result from severe stenosis and ventricular dysfunction.

Homocysteine as a biomarker of physical activity and exercise tolerance in adolescent children

Purpose: To determine the homocysteine content in children and adolescents with different levels of physical activity, to establish the relationship between homocysteine content, indicators of physical development, level of physical activity and tolerance to physical activity in adolescence. Material and Methods. We examined 83 children aged 11 to 17 years, who were examined by a pediatrician, an endocrinologist, and the girls by a pediatric gynecologist. The study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Committee on Bioethics and Deontology. Height, body weight and body mass index were assessed; physical activity tolerance by the Ruffier test; physical activity was assessed using a questionnaire; serum homocysteine was determined by enzyme-linked immunosorbent assay. Results. 81% of adolescents with high physical activity had regular sports training at least three times a week. In the group with low physical fitness, only 25.6 % attended sports sections, and 44.2 % of adolescents were completely physically inactive. The level of homocysteine in the blood did not depend on the sex of adolescents and physical development. Moderate hyperhomocysteinemia was detected in 41 adolescents, 68.3 % of whom had poor and low exercise tolerance and/or low physical activity. Statistically significantly higher homocysteine levels were observed in children with low physical activity (p<0.05), those who did not have sports training (p=0.027) or had reduced adaptation to physical activity (p<0.01). Conclusions. The level of homocysteine in the blood serum of adolescents did not depend on gender, physical development and the presence of somatic pathology. Low physical activity of adolescents is accompanied by increased levels of homocysteine in the blood. On the contrary, adolescents with high physical activity have lower levels. The lowest levels of homocysteine are observed in adolescents with good to excellent exercise tolerance. Unsatisfactory and weak Ruffier test results are associated with elevated homocysteine levels in adolescents

Poor cardiac output reserve in pulmonary arterial hypertension is associated with right ventricular stiffness and impaired interventricular dependence.

Pulmonary arterial hypertension (PAH) is characterised by poor exercise tolerance. The contribution of right ventricular (RV) diastolic function to the augmentation of cardiac output during exercise is not known. This study leverages pressure-volume (P-V) loop analysis to characterise the impact of RV diastology on poor flow augmentation during exercise in PAH. RV P-V loops were measured in 41 PAH patients at rest and during supine bike exercise. Patients were stratified by median change in cardiac index (CI) during exercise into two groups: high and low CI reserve. Indices of diastolic function (end-diastolic elastance (E ed)) and ventricular interdependence (left ventricular transmural pressure (LVTMP)) were compared at matched exercise stages. Compared to patients with high CI reserve, those with low reserve exhibited lower exercise stroke volume (36 versus 49 mL·m-2; p=0.0001), with higher associated exercise afterload (effective arterial elastance (E a) 1.76 versus 0.90 mmHg·mL-1; p<0.0001), RV stiffness (E ed 0.68 versus 0.26 mmHg·mL-1; p=0.003) and right-sided pressures (right atrial pressure 14 versus 8 mmHg; p=0.002). Higher right-sided pressures led to significantly lower LV filling among the low CI reserve subjects (LVTMP -4.6 versus 3.2 mmHg; p=0.0001). Interestingly, low exercise flow reserve correlated significantly with high afterload and RV stiffness, but not with RV contractility nor RV-PA coupling. Patients with poor exercise CI reserve exhibit poor exercise RV afterload, stiffness and right-sided filling pressures that depress LV filling and stroke work. High afterload and RV stiffness were the best correlates to low flow reserve in PAH. Exercise unmasked significant pathophysiological PAH differences unapparent at rest.

Mental fatigue and chronic fatigue syndrome in clinical practice

Fatigue is an extremely disabling symptom both in healthy people and in various diseases. Physical fatigue is characterized by limitations in physical functioning, while mental/cognitive fatigue involves difficulties in concentrating and performing cognitive tasks. Mental and physical fatigue exist in both pathological and physiological fatigue. Fatigue is primarily an adaptive physiological process. It is a signal to have a rest and helps conserve energy to prevent injury, which can be useful after intense work, or when the body’s defenses need to be redistributed, for example, during infectious disease. It is important to distinguish between fatigue or tiredness and chronic fatigue syndrome in clinical practice. Chronic fatigue syndrome has multisystem manifestations and affects millions of people globally. Although the exact aetiology of chronic fatigue syndrome is uncertain, the studies point to neurological, immunological, autonomic and energy disorders. The main sings of chronic fatigue syndrome are debilitating fatigue that is worsened by activity, poor exercise tolerance, unrefreshing sleep and cognitive impairment. Reduced information processing speed is the most common cognitive impairment in chronic fatigue syndrome. Other manifestations include decreased reaction time, working memory, and attention. These symptoms must persist for at least 3–6 months for a diagnosis to be made. As there are no specific tests for chronic fatigue syndrome, a diagnosis can be established on the basis of a medical history and physical examination.Although there are no standards-based methods specific to chronic fatigue syndrome, clinicians can reduce the severity of symptoms using pharmacological and non-pharmacological treatment approaches that have proved their efficacy in clinical practice. In particular, nootropics are widely used in asthenic conditions and chronic fatigue syndrome. Fonturacetam is a nootropic drug that directly activates brain integration activities, promotes memory consolidation, and improves concentration and mental activity.

Reference values for leg effort during incremental cycle ergometry in non-trained healthy men and women, aged 19-85.

Heightened sensation of leg effort contributes importantly to poor exercise tolerance in patient populations. We aim to provide a sex- and age-adjusted frame of reference to judge symptom's normalcy across progressively higher exercise intensities during incremental exercise. Two-hundred and seventy-five non-trained subjects (130 men) aged 19-85 prospectively underwent incremental cycle ergometry. After establishing centiles-based norms for Borg leg effort scores (0-10 category-ratio scale) versus work rate, exponential loss function identified the centile that best quantified the symptom's severity individually. Peak O2 uptake and work rate (% predicted) were used to threshold gradually higher symptom intensity categories. Leg effort-work rate increased as a function of age; women typically reported higher scores at a given age, particularly in the younger groups (p < 0.05). For instance, "heavy" (5) scores at the 95th centile were reported at ~200 W (<40 years) and ~90 W (≥70 years) in men versus ~130 W and ~70 W in women, respectively. The following categories of leg effort severity were associated with progressively lower exercise capacity: ≤50th ("mild"), >50th to <75th ("moderate"), ≥75th to <95th ("severe"), and ≥ 95th ("very severe") (p < 0.05). Although most subjects reporting peak scores <5 were in "mild" range, higher scores were not predictive of the other categories (p > 0.05). This novel frame of reference for 0-10 Borg leg effort, which considers its cumulative burden across increasingly higher exercise intensities, might prove valuable to judging symptom's normalcy, quantifying its severity, and assessing the effects of interventions in clinical populations.

Crampi muscolari, ipercpkemia e fenomeno "Second wind": la malattia di McArdle

The case of a 12-year-old girl presenting with poor exercise tolerance, muscular cramps and CPK high levels is described.The diagnosis of McArdle disease was eventually made due to the classic “second wind” sign.

Fizička aktivnost i srčana slabost sa očuvanom ejekcionom frakcijom leve komore

Heart failure with preserved left ventricular ejection fraction (HFpEF) is a clinical syndrome in which the structure and the function of the heart are damaged, with stiffness of the heart muscle, increased pressures in diastole and in the pulmonary circulation. The latest understanding of HFpEF is that it is a systemic disease of the microcirculation with chronic inflammation and impaired cellular metabolism. The aim of this review was to determine the association between physical activity and HFpEF based on the available research. By summarizing the literature data, it was shown that a sedentary lifestyle represents a risk factor for HFpEF and that continuous physical activity prevents the occurrence of HFpEF, while in patients already suffering from HFpEF it increases functional capacity, as well as the quality of life, mainly due to the improvement of peripheral muscles oxidative metabolism. The impact of physical activity on improving the diastolic function of the heart in people with heart failure is still under research. Patients with HFpEF usually have poor exercise tolerance, thus an individualized prescription of physical activity is indicated in accordance with their capabilities, preferably a combination of aerobic training, strength exercises, balance and an adequate diet. The gold standard for the assessment of aerobic capacity is the cardiopulmonary exercise test, which allows the measurement of oxygen consumption, maximum heart rate, the first and the second anaerobic thresholds, parameters needed for dosing the intensity of physical exercise.

Ayurvedic management of Sutika shotha (Post-Partum Thyroiditis): A case report

Post-Partum Thyroiditis (PPT) is an autoimmune disorder characterized by lymphocytic infiltration of the thyroid gland, leading to transient thyrotoxicosis followed by hypothyroidism. This condition typically occurs within the 1st year after childbirth. In this case study, the management of a 37-year-old lactating female who exhibited symptoms of fatigue, weight gain, joint pain, indigestion, swelling on lower limbs, constipation, dry skin, depression, and poor exercise tolerance is presented. The subclinical diagnosis revealed PPT as the underlying issue. The patient was diagnosed as Sutika shotha as per the clinical signs and symptoms and treated with an Ayurvedic approach, involving the administration of Varunadi kashaya, Gokshuradi guggulu, and Erandabhrishta haritaki churna for a period of three months. As the symptoms were mildly improved, the patient was planned for Panchakarma (~five internal bio-cleansing therapies). With regard to environmental conditions and strength of the patient, classical Virechana (~therapeutic purgation) was planned. After Virechana, the Thyroid-Stimulating Hormone (TSH) levels decreased from an initial value of 143.94 µIU/mL to 16.52 µIU/mL. Body mass index was reduced to 26.8 kg/m2 from 28.8 kg/m2. Thereafter, the patient was prescribed the Shamana aushadha (~palliative medicines) for approximately six months duration leading to a further reduction in TSH levels to the normal range (2.84 µIU/mL) and an improvement in the clinical symptoms of the patient. This case study highlights the potential of classical Ayurvedic approaches in managing PPT and restoring thyroid function, providing valuable insights into management strategies for Sutika shotha (PPT).

Neural network analysis of pharyngeal sounds can detect obstructive upper respiratory disease in brachycephalic dogs.

Brachycephalic obstructive airway syndrome (BOAS) is a highly prevalent respiratory disease affecting popular short-faced dog breeds such as Pugs and French bulldogs. BOAS causes significant morbidity, leading to poor exercise tolerance, sleep disorders and a shortened lifespan. Despite its severity, the disease is commonly missed by owners or disregarded by veterinary practitioners. A key clinical sign of BOAS is stertor, a low-frequency snoring sound. In recent years, a functional grading scheme has been introduced to semi-objectively grade BOAS based on the presence of stertor and other abnormal signs. However, correctly grading stertor requires significant experience and adding an objective component would aid accuracy and repeatability. This study proposes a recurrent neural network model to automatically detect and grade stertor in laryngeal electronic stethoscope recordings. The model is developed using a novel dataset of 665 labelled recordings taken from 341 dogs with diverse BOAS clinical signs. Evaluated via nested cross validation, the neural network predicts the presence of clinically significant BOAS with an area under the receiving operating characteristic of 0.85, an operating sensitivity of 71% and a specificity of 86%. The algorithm could enable widespread screening for BOAS to be conducted by both owners and veterinarians, improving treatment and breeding decisions.

Variable phenotypes and outcomes associated with the MMACHC c.482G > A mutation: follow-up in a large CblC disease cohort

BackgroundThe aim of this study was to characterize the variable phenotypes and outcomes associated with the methylmalonic aciduria and homocystinuria type C protein gene (MMACHC) c.482G > A mutation in 195 Chinese cases with CblC disease.MethodsWe carried out a national, retrospective multicenter study of 195 Chinese patients with CblC disease attributable to the MMACHC c.482G > A variant either in a homozygous or compound heterozygous state. The control group consisted of 200 patients diagnosed with CblC disease who did not possess the c.482G > A mutation. Clinical features, including disease onset, symptoms, biochemical metabolites, gene mutation, and follow-up outcomes were reviewed and analyzed in detail. The median follow-up period spanned 3 years and 8 months, with a range of 1 year and 2 months to 12 years and 10 months.ResultsAmong 195 patients carrying the c.482G > A variant, 125 (64.1%) cases were diagnosed by newborn screening (NBS), 60 (30.8%) cases were detected due to disease onset, and 10 (5.1%) cases were identified from sibling diagnoses. One hundred and seventeen (93.6%) individuals who were diagnosed by NBS, and nine patients who came from sibling diagnoses remained asymptomatic in this study. From 69 symptomatic patients of the c.482G > A group, more patients presented with later onset, and the top six common clinical symptoms at disease onset were developmental delay (59.4%), lower limb weakness and poor exercise tolerance (50.7%), cognitive decline (37.7%), gait instability and abnormal posture (36.2%), seizures (26.1%), and psychiatric and behavioral disturbances (24.6%). In the 159 symptomatic patients lacking c.482G > A variants, the most frequently observed clinical manifestations at disease onset included developmental delay (81.8%), lethargy and feeding difficulty (62.9%), lower limb weakness and poor exercise tolerance (54.7%), prolonged neonatal jaundice (51.6%), vomiting (47.2%), and seizures (32.7%). Before treatment, the levels of blood propionylcarnitine, propionylcarnitine/acetylcarnitine ratio, and homocysteine in the c.482G > A group were significantly lower (P < 0.05) than those in the non-c.482G > A group, while the concentration of urinary methylmalonic acid was slightly lower (P > 0.05). The degree of decline in the above metabolites after treatment in different groups significantly differed in both plasma total homocysteine values and urinary methylmalonic acid levels (P < 0.05). In patients carrying the c.482G > A variant compared with the non-c.428G > A group, there were markedly lower rates of mortality (0.5% vs. 2.0%) and developmental delay (20.5% vs. 65.5%). When compared with individuals diagnosed due to disease onset, those identified through NBS in either group exhibited a reduced proportion of disease onset (6.7% vs. 100% in the c.482G > A group, 54.4% vs. 100% in the non-c.482G > A group), lower mortality (0.0% vs. 1.7% in the c.482G > A group, 0.0% vs. 3.6% in the non-c.482G > A group), and had a higher percentage of patients exhibiting normal psychomotor and language development (99.3% vs. 33.3% in the c.482G > A group, 58.9% vs. 10.9% in the non-c.482G > A group).ConclusionsThe c.482G > A variant in MMACHC is associated with late-onset and milder phenotypes of CblC disease. Patients with this mutation tend to have a relatively better response to hydroxocobalamin, better metabolic control, and more favorable neurological outcomes. NBS and other appropriate pre-symptomatic treatments seem to be helpful in early diagnosis, resulting in favorable clinical outcomes.CNU96JjhPhuCQHh9ViZTVJVideo (MP4 136794 kb)

Patient-Reported Outcomes of Accelerated Aging: A Novel Approach to Investigate Second Cancer Risk in Adolescent and Young Adult (18-39 Years) Cancer Survivors.

Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and has been described clinically by 6 indicators; fatigue, low quality of sleep, low mood, lack of motivation, subjective memory complaints, and poor exercise tolerance. Using patient-reported outcomes, we aimed to identify clusters of accelerated aging among AYA cancer survivors and to investigate their association with second cancer development. Patient, tumor, and treatment data were obtained from the Netherlands Cancer Registry. Patient-reported clinical indicators and second cancer data were obtained from the SURVivors (5-20 years) of cancer in AYAs (SURVAYA) questionnaire study between 1999 and 2015. Latent class and multivariable logistic regression analyses were performed. In total, n = 3734 AYA survivors with known second cancer status (n = 278 [7.4%] second cancers) were included. Four latent clusters were identified and named based on their clinical indicator features; (1) high accelerated aging (31.3%), (2) intermediate accelerated aging without poor exercise tolerance (15.1%), (3) intermediate accelerated aging without lack of motivation (27.4%), and (4) low accelerated aging (26.2%). AYAs in the high accelerated aging cluster were more likely to have second cancer (odds ratio: 1.6; 95% CI, 1.1-2.3) compared to the low accelerated aging cluster. AYAs with a higher burden of accelerated aging were more likely to develop a second cancer. Validation of the clinical indicators and how to best capture them is needed to improve (early) detection of AYAs at high risk of developing second cancer.

Exploring the Iceberg: Detection and Management of Isolated Interrupted Aortic Arch and Associated Hypertension- A Rare Entity

Objectives: Prompt diagnosis and management of hypertension, particularly in younger patients, are crucial to reducing complications, mortality, and expenses. A thorough history and careful physical examination are key steps. This article illustrates one such unusual case that had a subtle presentation and went undiagnosed until it was brought to our attention.&#x0D; Methodology: A 30-year-old male patient with a history of fatigue, poor exercise tolerance, and mild headaches was diagnosed with hypertension. He was commenced on amlodipine and had no family history of cardiac diseases or secondary hypertension. The patient appeared weak and thin, with a BMI of 16.6 kg/m2. His radial pulse was regular and 98 bpm, and his brachial blood pressure was recorded at 190/90 mmHg. Further examination revealed weak lower limb pulses, a radio-femoral delay, and an ankle blood pressure of 100/60 mmHg. A 3/6 systolic murmur was noted at the aortic area. Routine laboratory investigations revealed a chest x-ray showing notching of the ribs and an absent aortic knob. A transthoracic echocardiogram was performed, but it did not provide conclusive results. A CT angiography of the chest revealed a complete interruption of the aorta just below the left subclavian artery in a "rat tail fashion." The aortic valve was normal, and no other aortic or cardiac pathology was found. The patient was diagnosed with IAA type A and surgical correction was suggested. Antihypertensive medication was given to achieve blood pressure control, and surgical correction was done involving end-to-end anastomosis. The patient's postoperative period was uneventful, and at four weeks, his symptoms subsided, and his blood pressure was 130/80 mmHg without antihypertensive medications.&#x0D; Results: The patient had an interrupted Aortic Arch type A and underwent treatment with antihypertensive medications and surgical correction. After a month, symptoms subsided, blood pressure was 130/80 mmHg, and pulses were bilaterally normal. Post-op CT Aortogram showed good anatomic continuity and no complications.&#x0D; Conclusion: Mild symptoms might only be the tip of an iceberg, calling for further exploration. IAA, despite its rarity, should be considered a potential cause of hypertension.

The role of the peripheral chemoreceptor reflex in non-hospitalised patients with post-COVID-19 syndrome

Abstract Background Long COVID (post COVID-19 syndrome) is a common debilitating illness. Little is known regarding the underlying mechanisms driving ongoing symptoms, which include lethargy, breathlessness, dysregulated breathing, and exercise intolerance. The carotid body is important in the control of breathing, is abundant in ACE2 (cell entry mechanism for SARS-CoV-2) and is known to drive similar symptoms in patients with heart failure (HF). We hypothesised that the carotid chemoreflex becomes hyperreactive in patients with long COVID-19 syndrome, which could be important in driving several ongoing symptoms. Purpose We aimed to examine whether carotid chemoreflex sensitivity was elevated in patients with long COVID (with initial mild-moderate symptoms) versus an age-matched control group and whether this could help to explain dysregulated breathing and poor exercise tolerance in long COVID. Methods Long COVID participants (n=14; 12F) were prospectively recruited from a tertiary cardiology long COVID clinic (after being cleared for cardiac conditions) and from advertising publicly. Patients were non-hospitalised and had received a diagnosis of long COVID via their GP or long COVID clinic. Participants had a positive PCR or sero-positive antibody test for their initial infection. Controls were healthy with no diagnosed comorbidities (n=14; 11F). Eight controls had a confirmed previous infection and did not develop ongoing symptoms. Participants completed baseline spirometry, a resting 12-lead electrocardiogram, and an incremental cardiopulmonary exercise test (CPET) to volitional exhaustion on a cycle ergometer. On a separate day, the carotid chemoreflex sensitivity was measured using the hypoxic ventilatory response (HVR) [1]. Averaged group data were compared using statistical software (GraphPad, Prism). Data are mean ± SD unless stated otherwise. Results Age and body mass index were similar between groups (Table 1). Resting spirometry indicated that lung function was similar between groups (Table 1). The long COVID group had a lower maximum volume of inspired oxygen (VO2 peak) and a similar maximum heart rate (as a % of predicted) vs. controls (Table 1). Ventilatory efficiency (VE/VCO2) slope, VE/VCO2 ratio at anaerobic threshold (AT), and VE/VCO2 nadir were higher in the long COVID group, indicating poor breathing efficiency, similar to the level observed in HF (Table 1) [2]. Finally, the HVR was elevated in the long COVID group (-0.45±0.23 l/min/SpO2%) versus the control group (-0.18±0.13 l/min/SpO2%, Figure 1, P=0.0007). The HVR correlated with the VE/VCO2 slope (r=0.54, P=0.0012). Conclusions These data suggest that the carotid chemoreflex is sensitised in people with long COVID and may help to explain dysregulated breathing in these patients. The carotid chemoreflex could be a viable target to help improve symptoms in people suffering with ongoing symptoms following even a mild original SARS-CoV-2 infection, but more research is needed.Table 1Figure 1

Abstract 16040: Atrial Fibrillation Status and Physical Rehabilitation in Older Patients With Acute Decompensated Heart Failure: An Analysis From the Rehab-HF Trial

Background: The REHAB-HF randomized, controlled trial demonstrated that a transitional, tailored, progressive rehabilitation intervention improved physical function, 6-minute walk distance, frailty, quality-of-life, and depression in older patients hospitalized for acute decompensated heart failure (ADHF). Atrial fibrillation (AF) is common in patients with HF and associated with poor exercise tolerance. However, exercise has proven safe and effective in improving quality of life in AF patients. It is unknown if AF impacts the benefit gained by rehabilitation intervention. Question: We hypothesized that patients with AF and ADHF would significantly improve physical function outcomes, and these improvements would not differ significantly from those gained by patients without AF. Methods: REHAB-HF enrolled 349 patients hospitalized for ADHF. Mean age was 72.7 ± 8.1 years. Participants were randomly assigned to the 12-week progressive rehabilitation intervention or attention control. The trial’s primary outcome was change in short physical performance battery (SPPB) score between baseline and 3 months. Secondary outcomes were clinical endpoints (rehospitalization or death). Results: AF was prevalent in 176 patients (50.4%). Participants with AF were significantly older than those without (74.4 ± 8.3 vs. 70.8 ± 7.5, p&lt;0.001) and had higher prevalence of HFpEF (58.5% vs 47.4%, p=0.037). Patients with and without AF had similar improvement in SPPB score (mean between-group difference, 1.5; 95% CI 0.4-2.5; p=0.001). There was no significant difference in mean SPPB between the two groups (p=0.98). KCCQ score and 6-minute walk distance significantly improved in patients with AF (p&lt;.05). The interaction P-values for 3-month outcomes by AF status were not significant (P &gt;0.1). There were no significant differences in deaths, all-cause rehospitalizations, or HF hospitalizations at 6 months. Conclusions: In older, hospitalized patients with ADHF, the presence of AF did not significantly affect the benefit of the transitional, tailored, progressive rehabilitation intervention. These findings suggest the intervention is safe to use to improve physical function and quality of life in patients hospitalized for ADHF regardless of AF status.

Abstract 12214: Large Left Atrial Infected Myxoma in a Healthy Patient With Intermittent Fever

Introduction: Infected myxomas represent a rare subset of cardiac myxomas. The diagnosis is classified as definite, probable, or possible based on microbiological and pathological findings. Prognosis is often favorable with early diagnosis and intervention. Case description: A 39-year-old female with a history of iron-deficiency anemia presented with three months of fever, poor exercise tolerance, 15-lb unintentional weight loss, and episodes of amaurosis fugax associated with upper extremity paresthesias. Her physical exam revealed tachycardia and a grade 3/6 apical holosystolic murmur. Her laboratory workup was notable for microcytic anemia, elevated inflammatory markers, and Streptococcus sanguinis bacteremia . Echocardiography showed left ventricular and left atrial dilation with normal systolic function and a 6.4x4.3 cm heterogenous left atrial mass adherent to the interatrial septum with prolapse across the mitral valve plane (Figure 1, panel A-B) associated with eccentric mitral regurgitation. She was managed with surgical resection and antibiotics. Pathology revealed myxomatous tissue and prominent plasma cell infiltrates, confirmatory of definite infected cardiac myxoma. Follow-up echocardiography showed residual mitral regurgitation due to mitral annular stretch from myxoma for which surgical intervention was deferred in the acute setting. Discussion: A definite diagnosis of infected myxoma is established with biopsy-proven myxoma, along with microorganism visualization or positive blood cultures with inflammatory cells on histopathology. Rare in occurrence, infected myxomas have been associated with a higher incidence of embolic events, sepsis, and shock compared to uninfected myxomas. Prognosis is favorable with prompt intervention. Increased awareness leading to earlier diagnosis and management is a priority for this subset of patients.

SAT087 Maternally Inherited Diabetes And Deafness: Support For SGLT2 Inhibitor Use

Abstract Disclosure: S. Pandya: None. K. Selk: None. Introduction: Maternally inherited diabetes and deafness (MIDD) is a rare genetic disease resulting from a mitochondrial mutation. There is a wide phenotypic expression secondary to heteroplasmy. The clinical manifestations of MIDD are hyperglycemia, sensorineural hearing loss, maculopathy, cardiac conduction defects, myopathy/poor exercise tolerance, and neuropathy. Diabetes mellitus generally occurs during the third decade of life, and there tends to be rapid progression to insulin therapy with reported earlier onset of microvascular complications. Here we present a case of MIDD successfully treated long-term with empagliflozin and linagliptin. Clinical Case: A 36-year-old male with sensorineural hearing loss presented with a 20-pound unintentional weight loss, polyphagia, and polydipsia. His blood glucose level was 300 mg/dL and HbA1c was 14.3%. His mother carried a diagnosis of type 2 diabetes mellitus and his grandmother had latent autoimmune diabetes of adulthood. Prior to presenting to endocrinology, he had been started on metformin, glipizide, and linagliptin with ongoing poor glycemic control. Given his presentation, family history, and lean habitus with BMI of 20, he was assessed for possible autoimmune diabetes. Testing for glutamic acid decarboxylase 65-kilodalton isoform antibody (GAD65), islet cell antibody, tyrosine phosphatase-related islet antigen 2 (IA2), and zinc transporter 8 antibody (ZNT8) was unrevealing. A C-peptide level was detectable but &amp;lt;1 ng/mL. His sulfonylurea was discontinued, and he was started on basal insulin with a dramatic improvement in his glycemic control. He was later able to discontinue insulin therapy. However, given poor exercise tolerance and his known hearing loss, he was seen by genetics where he underwent testing and was found to have a m.3243 A&amp;gt;G mutation in MT-TL1 gene making the diagnosis of MIDD. Metformin was discontinued due to a possible risk of lactic acidosis and sitagliptin was initiated. Due to hyperglycemia, empagliflozin was added and he was later transitioned to empagliflozin-linagliptin to reduce his pill burden. He has continued to have a1c levels of 6.5% or less for the last 3 years and periodic C-peptide measurements have been &amp;gt;1 ng/mL. Conclusion: Given MIDD is a rare form of monogenic diabetes, treatment tends to be individualized with many transitioning to insulin early in their disease course. Given the reported increased risk for microvascular complications, sodium-glucose cotransporter-2 (SGLT2) inhibitors are an attractive therapeutic agent. However, there is little literature on the use of these agents in MIDD and there is concern about the risk for diabetic ketoacidosis given insulin use is required by many afflicted individuals. This case highlights the safety of long-term empagliflozin in a patient with MIDD. Presentation: Saturday, June 17, 2023

SAT315 A Case Of PAI "Do Not Miss This Rare Cause"

Abstract Disclosure: R. Alshantti: None. C. Musurakis: None. U. Rafat: None. W. Akhter: None. J.L. Gilden: None. A. Moid: None. Background: Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a mutation in the ABCD1 gene, located at Xq28. This impairs beta-oxidation and breakdown of very long chain fatty acids (VLCFAs) which then accumulate in the CNS, adrenal cortex, and Leydig cells of the testes, leading to three main phenotypes of X-ALD: childhood cerebral ALD, adrenomyeloneuropathy AMN, and adrenal insufficiency (AI). AI presents in 47% of X-ALD cases by age 10 years. X-ALD represents a spectrum of phenotypes that vary in age of onset, severity, and clinical characteristic. AI may predate, occur simultaneously with, or follow the onset of the neurologic deterioration. While in the majority, it is inherited in an X-linked manner, at least 4.1% of individuals with X-ALD have a de novo pathogenic variant of ABCD1. Case Description: A 30-year-old male, previously healthy, was found to have adrenal nodule on CT renal during the evaluation of a transient episode of acute abdominal pain. Further evaluation of the adrenal nodule with a CT adrenal protocol showed a 1.5 cm x 1.0 cm right adrenal nodule, HU 22, washout of 66.7% consistent with an adrenal adenoma. Evaluation of adrenal hormones failed to show abnormal hypersecretion, but rather suggested insufficiency. Lab tests: RENIN FRZ PLS 45.76 ng/mL/h (0.25 - 5.82), ALDOSTERONE &amp;lt;1 ng/dL, ACTH &amp;gt;1250 pg/mL (0 - 47), SALIV CORT 0.06 mcg/dL, DHEAS 28.19 ug/dL (34.5 - 568.9). The patient was referred to endocrinology. Only reported symptom was poor exercise tolerance. Diagnosis of primary adrenal insufficiency was confirmed by low AM cortisol of 7.91 ug/dL, and very high ACTH of &amp;gt;1250 H pg/mL. He was started on glucocorticoid &amp; mineralocorticoid replacements. An evaluation to determine the etiology of PAI was conducted. The patient was not taking any medications or drugs. Family history was noncontributory. 21 OH Ab was negative. Quantiferron was negative. Our patient had no risk factors or clinical manifestations to suggest TB or fungal infections. No bleeding disorders. CT adrenal findings did not suggest infiltrative, infectious, hemorrhage, or malignant etiologies. Blood tests for VLCFAs showed elevations in phytanic, C22:0, C24:0, C26:0, C24/C22, &amp; C26/C22. These are consistent with X-linked adrenomyeloneuropathy. Genetic testing has confirmed the diagnosis; POSITIVE for a hemizygous pathogenic variant in ABCD1, consistent with a diagnosis of X-linked adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN). Conclusion: Our case highlights the importance of a comprehensive evaluation to determine the cause of PAI. When autoimmunity and infectious etiologies are ruled out in male patients, it is crucial to consider X- ALD regardless of age at presentation, family history, or presence/absence of neurologic symptoms. This diagnosis is particularly important not to miss, since X-ALD can have devastating implications not only for the patient but also the family. Presentation: Saturday, June 17, 2023

Dynamic Ventilatory Reserve During Incremental Exercise: Reference Values and Clinical Validation in Chronic Obstructive Pulmonary Disease.

Rationale: Ventilatory demand-capacity imbalance, as inferred based on a low ventilatory reserve, is currently assessed only at peak cardiopulmonary exercise testing (CPET). Peak ventilatory reserve, however, is poorly sensitive to the submaximal, dynamic mechanical ventilatory abnormalities that are key to dyspnea genesis and exercise intolerance. Objectives: After establishing sex- and age-corrected norms for dynamic ventilatory reserve at progressively higher work rates, we compared peak and dynamic ventilatory reserve for their ability to expose increased exertional dyspnea and poor exercise tolerance in mild to very severe chronic obstructive pulmonary disease (COPD). Methods: We analyzed resting functional and incremental CPET data from 275 controls (130 men, aged 19-85 yr) and 359 Global Initiative for Chronic Obstructive Lung Disease patients with stage 1-4 obstruction (203 men) who were prospectively recruited for previous ethically approved studies in three research centers. In addition to peak and dynamic ventilatory reserve (1 - [ventilation / estimated maximal voluntary ventilation] × 100), operating lung volumes and dyspnea scores (0-10 on the Borg scale) were obtained. Results: Dynamic ventilatory reserve was asymmetrically distributed in controls; thus, we calculated its centile distribution at every 20 W. The lower limit of normal (lower than the fifth centile) was consistently lower in women and older subjects. Peak and dynamic ventilatory reserve disagreed significantly in indicating an abnormally low test result in patients: whereas approximately 50% of those with a normal peak ventilatory reserve showed a reduced dynamic ventilatory reserve, the opposite was found in approximately 15% (P < 0.001). Irrespective of peak ventilatory reserve and COPD severity, patients who had a dynamic ventilatory reserve below the lower limit of normal at an isowork rate of 40 W had greater ventilatory requirements, prompting earlier attainment of critically low inspiratory reserve. Consequently, they reported higher dyspnea scores, showing poorer exercise tolerance compared with those with preserved dynamic ventilatory reserve. Conversely, patients with preserved dynamic ventilatory reserve but reduced peak ventilatory reserve reported the lowest dyspnea scores, showing the best exercise tolerance. Conclusions: Reduced submaximal dynamic ventilatory reserve, even in the setting of preserved peak ventilatory reserve, is a powerful predictor of exertional dyspnea and exercise intolerance in COPD. This new parameter of ventilatory demand-capacity mismatch may enhance the yield of clinical CPET in the investigation of activity-related breathlessness in individual patients with COPD and other prevalent cardiopulmonary diseases.

The Effect of Mechanotherapy and Virtual Reality on Cardiovascular Activity and the Severity of Shortness of Breath in Patients with Post COVID-19 Syndrome: A Prospective Randomized Study

INTRODUCTION. At present, there is an urgent need to develop modern rehabilitation programs for COVID-19 patients with long-lasting residual symptoms of the disease, primarily from the cardiopulmonary system.&#x0D; AIM. To assess the impact of a comprehensive medical rehabilitation program using virtual reality technologies, robotic mechanotherapy with biofeedback and interactive balance therapy on the severity of hypoxic syndrome, shortness of breath and cardiovascular activity in patients who have undergone COVID-19 and have manifestations of post-COVID syndrome (long COVID).&#x0D; MATERIAL AND METHODS. The study sample consisted of 120 patients aged 40 to 70 years who had suffered COVID-19 within 16 months prior to inclusion in the study and had manifestations of SPCN, who were randomized into 2 groups. In the main group (n = 60), a new complex of medical rehabilitation was prescribed against the background of basic treatment: 1) sessions on the robotic biofeedback simulator for lower limb muscle training Con-Trex, #10; 2) balance therapy (sensorimotor training) using the biofeedback simulator Stabilan 012, #10; 3) training on the rehabilitation interactive markerless system with virtual reality technology Nirvana, #10. In the control group (n = 60) patients received only basic treatment: 1) a special complex of therapeutic gymnastics performed in the hall with a physical therapy instructor, № 10; 2) low-intensity laser radiation, № 10; 3) speleo-exposure, № 10; 4) medical massage on the chest area, № 10. Research methods included clinical examination, anamnesis collection and cardiopulmonary testing and assessment of dyspnea severity before the beginning of rehabilitation and immediately after its completion.&#x0D; RESULTS AND DISCUSSION. In the period from 1 to 6 months after COVID-19, 90.0 % of patients had dyspnea, as well as a decrease in peak oxygen consumption and high values of heart rate (HR), systolic and diastolic blood pressure (BP) at peak exercise. The application of a new complex of medical rehabilitation in patients with post-COVID disorder syndrome contributed to a more significant, than in the standard method of rehabilitation, increase in cardiorespiratory endurance, which is manifested in the increase in the maximum work performed by 12.9 % and oxygen consumption of the first ventilation threshold by 6.3 % and in the decrease in diastolic BP at peak load by an average of 7 mm Hg. hg according to cardiopulmonary testing, as well as an increase in the proportion of patients with mild (up to 60.0 %) or no dyspnoea (up to 26 %) and a decrease in the number of patients with moderate dyspnoea (up to 13.3 %), severe and very severe dyspnoea (up to 0 %). Most of the authors in their studies also note a high frequency of shortness of breath, along with such manifestations of post- COVID-19 syndrome as general weakness, poor exercise tolerance.&#x0D; CONCLUSION. A new comprehensive medical rehabilitation program using virtual reality technologies, robotic mechanotherapy with biofeedback and interactive balance therapy are recommended to reduce the severity of hypoxic syndrome and dyspnea and improve cardiovascular performance in patients with post-COVID syndrome.