Exertional Fatigue Research Articles

Aortopulmonary Window in Association with Subpulmonic Ventricular Septal Defect and Non Compaction of Left Ventricle

Aortopulmonary window (APW) is a rare congenital cardiac anomaly, which clinically mimics patent ductusarteriosus (PDA). A girl who was diagnosed tohave congenital heart disease (CHD) at the age of four years presented to us at the age of 10 years with exertional dyspnoea and fatigue. She was clinically diagnosed as PDA with pulmonary artery hypertension (PAH) Two-dimensional and colour Doppler echocardiography showed a type II aortopulmonary window and a large inlet type of subpulmonic ventricular septal defect (VSD) with non-compaction of left ventricle. The diagnosis was confirmed by cardiac catheterization and angiography. This is an interesting case of type II APW with rare association that can be missed clinically, but can be diagnosed by meticulous echocardiogram. We herein report a rare case of aortopulmonary window associated with a subpulmonic ventricular septal defect and leftventicle non compaction (LVNC). Key words: Aortopulmonary window, Patentductus arteriosis, 2D Echocardiography, Left ventricular noncompaction, Subpulmonic ventricular septal defect.

Effects of OXPHOS complex deficiencies and ESA dysfunction in working intact skeletal muscle: implications for mitochondrial myopathies

The effects of inborn oxidative phosphorylation (OXPHOS) complex deficiencies or possible each-step activation (ESA) dysfunction on the bioenergetic system in working intact skeletal muscle are studied using a computer model of OXPHOS published previously. The curves representing the dependencies of V˙O2 and metabolite concentrations on single complex activity, entire OXPHOS activity or ESA intensity exhibit a characteristic threshold at some OXPHOS complex activity/ESA intensity. This threshold for V˙O2 of single complex activities is significantly lower in intact muscle during moderate and heavy work, than in isolated mitochondria in state 3. Metabolite concentrations and pH in working muscle start to change significantly at much higher OXPHOS complex activities/ESA intensities than V˙O2. The effect of entire OXPHOS deficiency or ESA dysfunction is potentially much stronger than the effect of a single complex deficiency. Implications of these findings for the genesis of mitochondrial myopathies are discussed. It is concluded that V˙O2 in state 3 and its dependence on complex activity in isolated mitochondria is not a universal quantitative determinant of the effect of mitochondrial dysfunctions in vivo. Moderate and severe mitochondria dysfunctions are defined: the former affect significantly only metabolite concentrations and pH, while the latter also decrease significantly V˙O2 in intact skeletal muscle during work. The dysfunction-caused decrease in V˙O2/oxidative ATP synthesis flux, disturbance of metabolite homeostasis, elevated ROS production and anaerobic glycolysis recruitment can account for such mitochondrial myopathy symptoms as muscle weakness, exercise intolerance (exertional fatigue) and lactic acidosis.

The striated muscles in pulmonary arterial hypertension: adaptations beyond the right ventricle.

Pulmonary arterial hypertension (PAH) is a fatal lung disease characterised by progressive remodelling of the small pulmonary vessels. The daily-life activities of patients with PAH are severely limited by exertional fatigue and dyspnoea. Typically, these symptoms have been explained by right heart failure. However, an increasing number of studies reveal that the impact of the PAH reaches further than the pulmonary circulation. Striated muscles other than the right ventricle are affected in PAH, such as the left ventricle, the diaphragm and peripheral skeletal muscles. Alterations in these striated muscles are associated with exercise intolerance and reduced quality of life. In this Back to Basics article on striated muscle function in PAH, we provide insight into the pathophysiological mechanisms causing muscle dysfunction in PAH and discuss potential new therapeutic strategies to restore muscle dysfunction.

A Rare Case With Pulmonary and Cardiac Inflammatory Myofibroblastic Tumor

A 9-year-old girl was admitted to the hospital because of exertional dyspnea, intermittent fever and fatigue, and inappetence for 3 months. She did not have chills or night sweats and had not lost weight. She was in mild respiratory distress with a respiratory rate of 34 breaths/min and a heart rate of 100 bpm that was regular in rhythm. Her blood pressure was 94/62 mm Hg. Cardiac auscultation revealed a distinct early diastolic click followed by a grade 2/5 diastolic decrescendo murmur at the apex that was variable in character with postural changes. Chest x-ray, posterior-anterior view, showed that the cardiothoracic ratio was increased. A high density was noted behind heart. The left lateral view showed an enlarged left atrium and abnormally high density at the region of lower left pulmonary hilar (Figure 1). Figure 1. Chest x-ray. A , Posterior-anterior view showed that the cardiothoracic ratio was increased, and a high density was noted behind the heart (arrow). B , Left lateral view showed an enlarged left atrium and an abnormally high density (arrow) at the region of the lower left pulmonary hilar. The ECG showed sinus rhythm, left atrium enlargement demonstrated by bifid P wave with >40 milliseconds between the 2 peaks and a total P-wave duration of >110 milliseconds in lead II. A biphasic P wave was seen with a terminal negative portion that was >40 milliseconds in duration and …

Prognostic Significance and Determinants of the 6-Min Walk Test in Patients With Heart Failure and Preserved Ejection Fraction

ObjectivesThis study sought to define the prognostic significance and clinical determinants of the 6-min walk distance (6-MWD) in affected patients. BackgroundSymptoms of exertional fatigue and dyspnea, as well as a reduced exercise tolerance, are cardinal features of pulmonary hypertension associated with heart failure and preserved ejection fraction (PH-HFpEF). Mechanisms limiting exercise capacity in this specific entity remain incompletely understood. MethodsConsecutive patients with PH-HFpEF, as confirmed by right heart catheter, were enrolled in our prospective registry. Hospitalization for HF and/or death for cardiac reasons were defined as primary outcome. Multiple regression models were constructed to establish determinants of the 6-MWD. For quantification of left ventricular (LV) extracellular matrix (ECM), myocardial biopsies were taken from 18 patients. ResultsBetween December 2010 and July 2013, 142 PH-HFpEF patients were included in the study. After a mean follow-up of 14.0 ± 10.0 months, 43 patients (30.3%) reached the combined endpoint. The 6-MWD was found to be an independent predictor of outcome and was influenced by a variety of clinical, echocardiographic, hemodynamic, laboratory, and pulmonary parameters. There was a significant inverse correlation between the 6-MWD and the extent of ECM in the LV myocardium. ConclusionsImpaired exercise capacity in PH-HFpEF patients is explained by cardiac and noncardiac factors. The 6-MWD predicts outcome and may be a useful endpoint in clinical trials.

Limitations of Chest Pain Categorization Models to Predict Coronary Artery Disease

We aimed to evaluate how chest pain categorization, currently used to assess the pretest probability of coronary artery disease (CAD), predicts the actual presence of CAD in a population of patients with stable symptoms. We studied 475 consecutive patients enrolled in the Evaluation of Integrated Cardiac Imaging for the Detection and Characterization of Ischemic Heart Disease study based on possible symptoms of CAD. Chest pain or discomfort was categorized as typical angina, atypical angina, or as nonanginal according to the guidelines. Exertional dyspnea and fatigue suspected to be angina equivalents were classified as atypical angina. Patients with a probability of CAD <20 or >90% based on age, gender, and symptoms were excluded. The end points of this substudy were significant CAD (defined by invasive coronary angiography as >50% reduction in lumen diameter in the left main stem or >70% stenosis in a major coronary vessel or 30% to 70% stenosis with fractional flow reserve ≤0.8), inducible myocardial ischemia at noninvasive stress imaging, and their association. Patients' symptoms had limited ability to predict the presence of significant CAD, global chi-square being 5.0. The inclusion of age increased global chi-square to 18.7 and gender increased it further to 51.1. Using inducible myocardial ischemia or the association of CAD with inducible ischemia as end points, the ability to predict these end points was again better for patient demographics than for patient symptoms. Thus, the ability of current models based on symptoms, age, and gender to predict the presence of CAD is mainly based on patient demographics as opposed to symptoms.

Iron supplementation effectively suppresses gastrocnemius muscle lesions to improve exercise capacity in chronic heart failure rats with anemia

ObjectiveFor patients with chronic heart failure (CHF), exertional fatigue is one of the most common and debilitating symptoms. However, the poor relationship between heart dysfunction and exercise capacity has been ascribed to peripheral abnormalities. Several previous studies confirmed that iron supplementation could significantly improve the exercise capacity of patients with CHF, although they did not analyze effects in the musculoskeletal system. The aim of this study was to investigate the effect of iron treatment on gastrocnemius muscles of CHF rats with anemia. MethodsMale Sprague-Dawley rats were subjected to coronary ligation to induce heart failure. At the same time, blood (1–1.5 mL) was withdrawn from the retro-orbital plexus once every week to induce anemia. After 6 wk of this process, iron dextran was administered to the CHF rats with anemia (CHFa rats) at the dose of 8, 16, 32, or 64 mg/kg every 2 d for 2 wk. ResultsIron dextran (8 mg/kg every 2 d) effectively improved hemodynamic parameters (P < 0.05) compared with CHFa rats. Similarly, this dose of iron dextran significantly reduced the ratio of heart weight to body weight (P < 0.01), whereas it significantly increased the distance run (m) to exhaustion (P < 0.01). Iron dextran effectively inhibited sarcoplasmic vacuolation and muscle atrophy of gastrocnemius muscles in CHFa rats, as evaluated by pathologic examinations. Other iron treatments, however, were found to be ineffective on the same parameters, so particular focus was placed on the iron dextran (8 mg/kg every 2 d) group in subsequent analyses. Consistently, phospho-p38 in gastrocnemius muscles of CHFa rats was markedly suppressed by iron dextran. Additionally, iron dextran significantly decreased c-fos and c-jun and up-regulated cellular FLICE-inhibitory protein expression levels.

Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells from individuals with chronic fatigue syndrome.

BackgroundPost exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS). Abnormalities of skeletal muscle function have been identified in some but not all patients with CFS. To try to limit potential confounders that might contribute to this clinical heterogeneity, we developed a novel in vitro system that allows comparison of AMP kinase (AMPK) activation and metabolic responses to exercise in cultured skeletal muscle cells from CFS patients and control subjects.MethodsSkeletal muscle cell cultures were established from 10 subjects with CFS and 7 age-matched controls, subjected to electrical pulse stimulation (EPS) for up to 24h and examined for changes associated with exercise.ResultsIn the basal state, CFS cultures showed increased myogenin expression but decreased IL6 secretion during differentiation compared with control cultures. Control cultures subjected to 16h EPS showed a significant increase in both AMPK phosphorylation and glucose uptake compared with unstimulated cells. In contrast, CFS cultures showed no increase in AMPK phosphorylation or glucose uptake after 16h EPS. However, glucose uptake remained responsive to insulin in the CFS cells pointing to an exercise-related defect. IL6 secretion in response to EPS was significantly reduced in CFS compared with control cultures at all time points measured.ConclusionEPS is an effective model for eliciting muscle contraction and the metabolic changes associated with exercise in cultured skeletal muscle cells. We found four main differences in cultured skeletal muscle cells from subjects with CFS; increased myogenin expression in the basal state, impaired activation of AMPK, impaired stimulation of glucose uptake and diminished release of IL6. The retention of these differences in cultured muscle cells from CFS subjects points to a genetic/epigenetic mechanism, and provides a system to identify novel therapeutic targets.

Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in McArdle disease using a mouse primary skeletal-muscle culture in vitro.

ABSTRACTMcArdle disease, also termed ‘glycogen storage disease type V’, is a disorder of skeletal muscle carbohydrate metabolism caused by inherited deficiency of the muscle-specific isoform of glycogen phosphorylase (GP-MM). It is an autosomic recessive disorder that is caused by mutations in the PYGM gene and typically presents with exercise intolerance, i.e. episodes of early exertional fatigue frequently accompanied by rhabdomyolysis and myoglobinuria. Muscle biopsies from affected individuals contain subsarcolemmal deposits of glycogen. Besides GP-MM, two other GP isoforms have been described: the liver (GP-LL) and brain (GP-BB) isoforms, which are encoded by the PYGL and PYGB genes, respectively; GP-BB is the main GP isoform found in human and rat foetal tissues, including the muscle, although its postnatal expression is dramatically reduced in the vast majority of differentiated tissues with the exception of brain and heart, where it remains as the major isoform. We developed a cell culture model from knock-in McArdle mice that mimics the glycogen accumulation and GP-MM deficiency observed in skeletal muscle from individuals with McArdle disease. We treated mouse primary skeletal muscle cultures in vitro with sodium valproate (VPA), a histone deacetylase inhibitor. After VPA treatment, myotubes expressed GP-BB and a dose-dependent decrease in glycogen accumulation was also observed. Thus, this in vitro model could be useful for high-throughput screening of new drugs to treat this disease. The immortalization of these primary skeletal muscle cultures could provide a never-ending source of cells for this experimental model. Furthermore, VPA could be considered as a gene-expression modulator, allowing compensatory expression of GP-BB and decreased glycogen accumulation in skeletal muscle of individuals with McArdle disease.

Exercise-Induced Pulmonary Artery Hypertension in a Patient with Compensated Cardiac Disease: Hemodynamic and Functional Response to Sildenafil Therapy

We describe the case of a 54-year-old man who presented with exertional dyspnea and fatigue that had worsened over the preceding 2 years, despite a normally functioning bioprosthetic aortic valve and stable, mild left ventricular dysfunction (left ventricular ejection fraction, 0.45). His symptoms could not be explained by physical examination, an extensive biochemical profile, or multiple cardiac and pulmonary investigations. However, abnormal cardiopulmonary exercise test results and a right heart catheterization-combined with the use of a symptom-limited, bedside bicycle ergometer-revealed that the patient's exercise-induced pulmonary artery hypertension was out of proportion to his compensated left heart disease. A trial of sildenafil therapy resulted in objective improvements in hemodynamic values and functional class.

Rare Case of Triatrial Heart with Unroofed Coronary Sinus

Triatrial heart is a rare congenital abnormality, reported in 0.4% of patients with congenital heart disease [1], and in less than 0.1% of clinically diagnosed cardiopathies [2]. First described by Church in 1868, the name “cor triatriatum” was given by Borst in 1905 [3]. It involves usually the left atrium (cor triatriatum sinister) and rarely the right atrium (cor triatriatum dexter). In the pediatric population may be associated with major congenital cardiac lesions such as tetralogy of Fallot, double outlet right ventricle, coarctation of the aorta, partial anomalous pulmonary venous connection, persistent left superior vena cava with unroofed coronary sinus, ventricular septal defect, atrioventricular septal defect, and common atrioventricular canal [4]. Clinical manifestations depend upon the size of the opening in the septum and the presence of associated congenital cardiac defects. We report a case of 5 years old girl who presented with history of exertional dyspnea ,fatigue and cyanosis. Echocardiogram done showed membrane attached laterally to the junction of the left upper pulmonic vein and left atrial appendage, dividing the left atrium into 2 chambers (Figure 1). The proximal chamber receives blood from the pulmonary veins and the distal chamber contains the left atrial appendage and mitral valve with single fenestration communicating both chambers (Figure 2). Contrast echo was done in view of cyanosis with agitated saline showed early appearance of bubbles in left atrium before right atrium suggestive of unroofed coronary sinus. Left sided superior venacava (SVC) was also seen. Diagnosis of cor-triatrium sinistrum with unroofed coronary sinus and left SVC was made and surgery was advised. Diagnosis of cor triatriatum is frequently made with considerable delay due to rarity of the condition and presenting signs and symptoms that mimic other more common cardiac or pulmonary disorders. A high index of suspicion can prevent delayed diagnosis and unfavorable outcomes.

Phenazopyridine‐Induced Hemolytic Anemia in Advanced Kidney Disease

Phenazopyridine‐Induced Hemolytic Anemia in Advanced Kidney Disease

The hemodynamic basis of exercise intolerance in tricuspid regurgitation.

Patients with severe tricuspid regurgitation (TR) frequently present with exertional fatigue and dyspnea, but the hemodynamic basis for exercise limitation in people with TR remains unclear. Twelve subjects with normal left ventricular (LV) ejection fraction and grade ≥3 TR underwent high-fidelity invasive hemodynamic exercise testing with simultaneous expired gas analysis and were compared with 13 age- and sex-matched controls. At rest, TR subjects had lower pulmonary blood flow (3.6±0.4 versus 5.1±1.9 L/min; P=0.01), increased right atrial pressure (12±5 versus 4±1 mm Hg; P=0.0002), and higher pulmonary capillary wedge pressure (17±5 versus 9±3 mm Hg; P=0.0001). However, LV transmural pressure (pulmonary capillary wedge pressure-right atrial pressure), which reflects LV preload independent of right heart congestion and pericardial restraint, was similar in TR and controls (6±3 versus 4±2 mm Hg; P=0.3). With exercise, TR subjects displayed lower peak VO2 (10.3±2.8 versus 13.8±4.2 mL/min per kg; P=0.02), lower pulmonary blood flow (6.4±1.3 versus 10.3±3.3 L/min; P=0.001), and less increase in pulmonary blood flow relative to VO2 (+4.6±1.1vs +6.2±0.7; P=0.001). TR subjects displayed higher pulmonary capillary wedge pressure with exercise, but this was solely because of RA hypertension (27±9 versus 8±3 mm Hg; P<0.0001), because LV transmural pressure dropped with exercise in subjects with TR (-5±6 versus +3±3 mm Hg; P=0.0007), suggesting inadequate LV diastolic filling, despite high pulmonary capillary wedge pressure. Impaired exercise capacity in people with severe TR is related to low cardiac output reserve relative to metabolic needs, coupled with elevated systemic and pulmonary venous pressures. Left heart pressures are elevated with exercise in subjects with TR, despite low LV preload, secondary to enhanced ventricular interaction.

Riboflavin responsive mitochondrial myopathy is a new phenotype of dihydrolipoamide dehydrogenase deficiency. The chaperon-like effect of vitamin B2

Dihydrolipoamide dehydrogenase (DLD, E3) is a flavoprotein common to pyruvate, α-ketoglutarate and branched-chain α-keto acid dehydrogenases. We found two novel DLD mutations (p.I40Lfs*4; p.G461E) in a 19year-old patient with lactic acidosis and a complex amino- and organic aciduria consistent with DLD deficiency, manifesting progressive exertional fatigue. Muscle biopsy showed mitochondrial proliferation and lack of DLD cross-reacting material. Riboflavin supplementation determined the complete resolution of exercise intolerance with the partial restoration of the DLD protein and disappearance of mitochondrial proliferation in the muscle. Morphological and functional studies support the riboflavin chaperon-like role in stabilizing DLD protein with rescue of its expression in the muscle.

Hemodynamic Basis for Exercise Intolerance in Right Heart Failure Due to Tricuspid Regurgitation

IntroductionTricuspid regurgitation (TR) is associated with symptoms of exertional fatigue and dyspnea, but the hemodynamic basis for functional limitation in TR is not well understood. Elevated pulmonary capillary wedge pressure (PCWP) is often assumed to indicate primary left heart failure, but may be observed with right heart congestion owing to pericardial restraint.Methods and Results15 patients with normal LVEF and grade ≥3 TR (10 women, age 76±7) underwent invasive supine exercise testing with expired gas analysis and were compared to 13 age and sex-matched controls. At rest, TR patients had lower cardiac output (CO) (3.9±1.4 vs 5.1±1.9 L/min; p=0.08), increased right atrial pressure (RAP) (12±5 vs 4±1 mmHg; p<0.0001) and higher PCWP (18±5 vs 9±3 mmHg; p<0.0001). However, left ventricular transmural pressure (LVTMP=PCWP-RAP), which better reflects LV preload independent of right heart and pericardial restraint, was similar in TR and controls (6±3 vs 4±2 mmHg, p=0.11). With exercise, TR patients displayed lower CO (6.3±1.5 vs 10.3±3.3 L/min; p=0.001) and VO2 (7.4±2.6 vs 11.1±4.2 ml/min/kg; p=0.01), with less increase in CO relative to VO2 (Figure 1). TR patients displayed higher PCWP with exercise (Figure 2), but this was solely due to right atrial hypertension (26±8 vs 8±3 mmHg, p<0.0001), as LVTMP fell with exercise, suggesting inadequate left heart filling despite high PCWP (Figure 3).ConclusionFigure 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3View Large Image Figure ViewerDownload Hi-res image Download (PPT) IntroductionTricuspid regurgitation (TR) is associated with symptoms of exertional fatigue and dyspnea, but the hemodynamic basis for functional limitation in TR is not well understood. Elevated pulmonary capillary wedge pressure (PCWP) is often assumed to indicate primary left heart failure, but may be observed with right heart congestion owing to pericardial restraint. Tricuspid regurgitation (TR) is associated with symptoms of exertional fatigue and dyspnea, but the hemodynamic basis for functional limitation in TR is not well understood. Elevated pulmonary capillary wedge pressure (PCWP) is often assumed to indicate primary left heart failure, but may be observed with right heart congestion owing to pericardial restraint. Methods and Results15 patients with normal LVEF and grade ≥3 TR (10 women, age 76±7) underwent invasive supine exercise testing with expired gas analysis and were compared to 13 age and sex-matched controls. At rest, TR patients had lower cardiac output (CO) (3.9±1.4 vs 5.1±1.9 L/min; p=0.08), increased right atrial pressure (RAP) (12±5 vs 4±1 mmHg; p<0.0001) and higher PCWP (18±5 vs 9±3 mmHg; p<0.0001). However, left ventricular transmural pressure (LVTMP=PCWP-RAP), which better reflects LV preload independent of right heart and pericardial restraint, was similar in TR and controls (6±3 vs 4±2 mmHg, p=0.11). With exercise, TR patients displayed lower CO (6.3±1.5 vs 10.3±3.3 L/min; p=0.001) and VO2 (7.4±2.6 vs 11.1±4.2 ml/min/kg; p=0.01), with less increase in CO relative to VO2 (Figure 1). TR patients displayed higher PCWP with exercise (Figure 2), but this was solely due to right atrial hypertension (26±8 vs 8±3 mmHg, p<0.0001), as LVTMP fell with exercise, suggesting inadequate left heart filling despite high PCWP (Figure 3). 15 patients with normal LVEF and grade ≥3 TR (10 women, age 76±7) underwent invasive supine exercise testing with expired gas analysis and were compared to 13 age and sex-matched controls. At rest, TR patients had lower cardiac output (CO) (3.9±1.4 vs 5.1±1.9 L/min; p=0.08), increased right atrial pressure (RAP) (12±5 vs 4±1 mmHg; p<0.0001) and higher PCWP (18±5 vs 9±3 mmHg; p<0.0001). However, left ventricular transmural pressure (LVTMP=PCWP-RAP), which better reflects LV preload independent of right heart and pericardial restraint, was similar in TR and controls (6±3 vs 4±2 mmHg, p=0.11). With exercise, TR patients displayed lower CO (6.3±1.5 vs 10.3±3.3 L/min; p=0.001) and VO2 (7.4±2.6 vs 11.1±4.2 ml/min/kg; p=0.01), with less increase in CO relative to VO2 (Figure 1). TR patients displayed higher PCWP with exercise (Figure 2), but this was solely due to right atrial hypertension (26±8 vs 8±3 mmHg, p<0.0001), as LVTMP fell with exercise, suggesting inadequate left heart filling despite high PCWP (Figure 3). ConclusionFigure 3View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Rheumatic Mitral Stenosis Complicated with Underlying Wolff-Parkinson-White Syndrome

Rheumatic mitral stenosis (MS) is an acquired valvular condition and is rarely associated with Wolff-Parkinson-White (WPW) syndrome. A 51-year-old Caucasian female with known MS presented with syncopal episodes, exertional fatigue and was noted to have atrial fi brillation (AF) with wide-QRS complexes. Old electrocardiogram revealed classical fi ndings of WPW syndrome and wide-QRS was believed to be due to pre-excited AF. Transthoracic echocardiogram demonstrated moderate MS and preserved systolic function. Electrophysiological studies revealed left anterolateral accessory pathway (AP) that was successfully ablated. Pre-excited AF manifests as cardiomyopathy, hemodynamic compromise, multiorgan dysfunction, and ventricular fi brillation. Catheter ablation of AP with or without restoration of sinus rhythm is the recommended therapy, with mitral valve replacement in the same or subsequent procedure. Key words: Mitral stenosis, radiofrequency ablation, rheumatic heart disease, Wolff-Parkinson-White syndrome.

Prognostic Significance and Determinants of the 6-minute Walk Test in Patients with Pulmonary Hypertension Associated with Heart Failure and Preserved Ejection Fraction

Introduction: Symptoms of exertional fatigue and dyspnea, as well as a reduced exercise tolerance are cardinal features of pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF). The aim of the present study was to define the prognostic significance and clinical determinants of the six-minute walking distance (6-MWD) in affected patients.

Profound lung remodeling in heart failure, a poorly understood phenomenon with a significant impact (715.6)

Exercise intolerance, characterized by dyspnea and early onset of exertional fatigue, is a chief complaint among patients with heart failure (HF). Limb muscle dysfunction is a known contributor to exercise intolerance, however, this phenomena does not explain dyspnea. Lung remodeling has been reported in end‐stage HF patients which could contribute to dyspnea and exercise intolerance, underscoring the importance and urgent need to better understand its role in HF. Our aim is to characterize the development of lung remodeling and its impact on exercise intolerance in HF. We hypothesize that lung remodeling occurs early in the development of HF, causing exercise‐induced hemoglobin (Hb) desaturation, affecting exercise performance. Methods: Male CD1 mice were subject to either transverse aortic constriction (TAC) or sham surgery. Exercise tolerance and Hb saturation were measured during a graded exercise test. The animals were sacrificed and lungs excised and fixed for histological evaluation. Results: Time to exhaustion was decreased by 40% in TAC. Hb saturation in TAC decreased during exercise while sham remained unchanged (p&lt;0.05). Hb levels were similar between sham and TAC animals. Lung compliance was significantly reduced in 9 week TAC compared to sham (p&lt;0.05), which further declined by 18 weeks (p&lt;0.01). Histological assessment revealed significant remodeling including a 43% increase in fibrosis (p&lt;0.01), marked inflammation and distended alveoli. Conclusions: Lung remodeling plays a significant yet under acknowledged role in exercise intolerance in HF patients. Grant Funding Source: Ontario Thoracic Society

An Unusual Cause of High-Output Heart Failure

In February, 2012, a 33-year-old man was admitted to our hospital because of exertional dyspnea, chest distress, and fatigue of 1 month duration. On admission, his blood pressure was 124/80 mm Hg and heart rate was 120 beats per minute. A chest examination detected no rales. Heart auscultation demonstrated accentuated first and second heart sounds, and grade 3/6 pansystolic ejection murmur in the mitral and tricuspid area. A grade 3/6 continuous machinery bruit over the left renal area was heard. His temperature ranged from 36.1°C to 38.3°C. He told us that he had undergone nephrectomy for contusion and laceration of left …

Pulmonary hypertension due to presence of isolated partial anomalous pulmonary venous connection: A case report

Anomalous pulmonary venous return is an uncommon congenital malformation which can be broadly categorized into partial or total, of which the former is more common. The anomaly is considered to be partial if some of the pulmonary veins drain into the systemic circulation and total if all the pulmonary veins drain into systemic circulation. Isolated partial anomalous pulmonary venous return (PAPVC) is an uncommon finding and is a very uncommon cause of pulmonary arterial hypertension. Whilst many patients with PAPVC remain asymptomatic, some may present at a later age with symptoms related to left-to-right shunt, pulmonary hypertension and right heart failure. We are presenting an interesting case report of an 18 years old patient who presented with exertional dyspnea and fatigue conforming to NYHA class II symptom status. Trans-esophageal echocardiography revealed isolated obstructive PAPVC as the cause for pulmonary hypertension without other demonstrable left-to-right shunts.