Physical Activity, Inactivity and Sleep in Individuals with Hypertrophic Cardiomyopathy.

Physical activity presents an important cornerstone in the management and care of individuals with hypertrophic cardiomyopathy (HCM). Twenty-one individuals with HCM (age: 52±15 years old, body mass index (BMI): 30±7 kg/m2) completed 7-day monitoring using wrist-worn triaxial accelerometers (GENEActiv, ActivInsights Ltd, UK) and were compared to age and sex-matched healthy controls (age: 51±14 years old, BMI: 25±4 kg/m2). For individuals with HCM, clinical parameters (left atrial diameter and volume, peak oxygen consumption, NTproBNP and Minnesota Living with Heart Failure (MLHF)) were correlated with accelerometry. After adjusting for BMI, individuals with HCM spent less time in moderate-vigorous physical activity (MVPA) (86 (55-138) vs. 140 (121-149) minutes/day, p<0.05) compared to healthy controls. Individuals with HCM engaged in fewer MVPA-5 min (6 (2-15) vs. 27 (23-37) minutes/day, p<0.01) and MVPA-10 min bouts (9 (0-19) vs. 35 (17-54) minutes/day, p<0.01) versus healthy controls. For HCM only, peak oxygen consumption was correlated with MVPA (r=0.60, p<0.01) and MVPA-5 min bouts (r=0.47, p<0.05). MLHF score was correlated with sleep duration (r=0.45, p<0.05). Individuals with HCM should be encouraged to engage in moderate-intensity physical activity bouts and reduce prolonged periods of inactivity in order to potentially improve exercise tolerance and reduce disease burden.

Current and novel echocardiographic assessment of left ventricular systolic function in aortic stenosis-A comprehensive review.

Aortic stenosis (AS) is a complex and progressive condition that can significantly reduce the quality of life and increase the incidence of premature mortality. Transthoracic echocardiography (TTE) is the gold standard imaging modality for the assessment of AS severity. While left ventricular ejection fraction (LVEF) derived from TTE is a very well-understood parameter, limitations such as high inter and intra-observer variability, insensitivity to sub-clinical dysfunction, and influence of loading conditions make LVEF a complicated and unreliable parameter. Myocardial deformation imaging has been identified as a promising parameter for identifying subclinical left ventricular dysfunction, however, this parameter is still afterload dependent. Myocardial Work is a promising novel assessment technique that accounts for afterload by combining the use of myocardial deformation imaging and non-invasive blood pressure to provide a more comprehensive assessment of mechanics beyond LVEF. This review evaluates the evidence for various echocardiographic assessment parameters used to quantify left ventricular function including myocardial work in patients with AS.

Noninvasive Assessment of Cardiac Output in Advanced Heart Failure and Heart Transplant Candidates Using the Bioreactance Method.

OBJECTIVES: The aim of the present study was to assess the validity and trending ability of the bioreactance method in estimating cardiac output at rest and in response to stress in advanced heart failure patients and heart transplant candidates. DESIGN: This was a prospective single-center study. SETTING: This study was conducted at the heart transplant center at the Freeman Hospital, Newcastle upon Tyne, UK. PARTICIPANTS: Eighteen patients with advanced chronic heart failure due to reduced left ventricular ejection fraction (19 ± 7%), and peak oxygen consumption 12.3 ± 3.9 mL/kg/min. INTERVENTIONS: Participants underwent right heart catheterization using the Swan-Ganz catheter. MEASUREMENTS AND MAIN RESULTS: Cardiac output was measured simultaneously using thermodilution and bioreactance at rest and during active straight leg raise test to volitional exertion. There was no significant difference in cardiac index values obtained by the thermodilution and bioreactance methods (2.26 ± 0.59 v 2.38 ± 0.50 L/min, p > 0.05) at rest and peak straight leg raise test (2.92 ± 0.77 v 3.01 ± 0.66 L/min, p > 0.05). In response to active leg raise test, thermodilution cardiac output increased by 22% and bioreactance by 21%. There was also a strong relationship between cardiac outputs from both methods at rest (r = 0.88, p < 0.01) and peak straight leg raise test (r = 0.92, p < 0.01). Cartesian plot analysis showed good trending ability of bioreactance compared with thermodilution (concordance rate = 93%) CONCLUSIONS: `Cardiac output measured by the bioreactance method is comparable to that from the thermodilution method. Bioreactance method may be used in clinical practice to assess hemodynamics and improve management of advanced heart failure patients undergoing heart transplant assessment.

Reproducibility of Inert Gas Rebreathing Method to Estimate Cardiac Output at Rest and During Cardiopulmonary Exercise Stress Testing.

The present study evaluated reproducibility of the inert gas rebreathing method to estimate cardiac output at rest and during cardiopulmonary exercise testing. Thirteen healthy subjects (10 males, 3 females, ages 23-32 years) performed maximal graded cardiopulmonary exercise stress test using a cycle ergometer on 2 occasions (Test 1 and Test 2). Participants cycled at 30-watts/3-min increments until peak exercise. Hemodynamic variables were assessed at rest and during different exercise intensities (i. e., 60, 120, 150, 180 watts) using an inert gas rebreathing technique. Cardiac output and stroke volume were not significantly different between the 2 tests at rest 7.4 (1.6) vs. 7.1 (1.2) liters min-1, p=0.54; 114 (28) vs. 108 (15) ml beat-1, p=0.63) and all stages of exercise. There was a significant positive relationship between Test 1 and Test 2 cardiac outputs when data obtained at rest and during exercise were combined (r=0.95, p<0.01 with coefficient of variation of 6.0%), at rest (r=0.90, p<0.01 with coefficient of variation of 5.1%), and during exercise (r=0.89, p<0.01 with coefficient of variation 3.3%). The mean difference and upper and lower limits of agreement between repeated measures of cardiac output at rest and peak exercise were 0.4 (-1.1 to 1.8) liter min-1 and 0.5 (-2.3 to 3.3) liter min-1, respectively. The inert gas rebreathing method demonstrates an acceptable level of test-retest reproducibility for estimating cardiac output at rest and during cardiopulmonary exercise testing at higher metabolic demands.

Heart rate variability and haemodynamic function in individuals with hypertrophic cardiomyopathy.

OBJECTIVES: Heart rate variability (HRV) is a measure of cardiac autonomic function. This study: (1) evaluated the differences in HRV and haemodynamic function between individuals with hypertrophic cardiomyopathy (HCM) and healthy controls, and (2) determined the relationship between HRV and haemodynamic variables in individuals with HCM. METHODS: Twenty-eight individuals with HCM (n = 7, females; age 54 ± 15 years; body mass index: 29 ± 5 kg/m2 ) and 28 matched healthy individuals (n = 7 females; age 54 ± 16 years; body mass index: 29 ± 5 kg/m2 ) completed 5-min HRV and haemodynamic measurements under resting (supine) conditions using bioimpedance technology. Frequency domain HRV measures (absolute and normalized low-frequency power (LF), high-frequency power (HF) and LF/HF ratio) and RR interval were recorded. RESULTS: Individuals with HCM demonstrated higher vagal activity (i.e., absolute unit of HF power (7.40 ± 2.50 vs. 6.03 ± 1.35 ms2 , p = 0.01) but lower RR interval (914 ± 178 vs. 1014 ± 168 ms, p = 0.03) compared to controls. Stroke volume (SV) index and cardiac index were lower in HCM compared with healthy individuals (SV, 33 ± 9 vs. 43 ± 7 ml /beat /m², p < 0.01; cardiac index,2.33 ± 0.42 vs. 3.57 ± 0.82 L/min/m2 , p < 0.01), but total peripheral resistance (TPR) was higher in HCM (3468 ± 1027 vs. 2953 ± 1050 dyn·s·m2 cm-5 , p = 0.03). HF power was significantly related to SV (r = -0.46, p < 0.01) and TPR (r = 0.28, p < 0.05) in HCM. CONCLUSIONS: Short-term frequency domain indices of HRV provide a feasible approach to assess autonomic function in individuals with HCM. Vagal activity, represented by HF power, is increased, and associated with peripheral resistance in individuals with HCM.

Application of non-invasive bioreactance to assess hemodynamic function in patients with hypertrophic cardiomyopathy.

Non-invasive technologies have become popular for the clinical evaluation of cardiac function. The present study evaluated hemodynamic response to cardiopulmonary exercise stress testing using bioreactance technology in patients with hypertrophic cardiomyopathy. The study included 29 patients with HCM (age 55 ± 15 years; 28% female) and 12 age (55 ± 14 years), and gender matched (25% female) healthy controls. All participants underwent maximal graded cardiopulmonary exercise stress testing with simultaneous non-invasive hemodynamic bioreactance and gas exchange. At rest, patients with HCM demonstrated significantly lower cardiac output (4.1 ± 1.3 vs. 6.1 ± 1.2 L/min; p < 0.001), stroke volume (61.5 ± 20.8 vs. 89.5 ± 19.8 mL/beat; p < 0.001), and cardiac power output (0.97 ± 0.3 vs. 1.4 ± 0.3watt; p < 0.001), compared to controls. At peak exercise, the following hemodynamic and metabolic variables were lower in HCM patients that is, heart rate (118 ± 29 vs. 156 ± 20 beats/min; p < 0.001), cardiac output (15.5 ± 5.8 vs. 20.5 ± 4.7 L/min; p = 0.017), cardiac power output (4.3 ± 1.6 vs. 5.9 ± 1.8 watts; p = 0.017), mean arterial blood pressure (126 ± 11 vs. 134 ± 10 mmHg; p = 0.039), and oxygen consumption (18.3 ± 6.0 vs. 30.5 ± 8.3 mL/kg/min; p < 0.001), respectively. Peak arteriovenous oxygen difference and stroke volume were not significantly different between HCM patients and healthy controls (11.2 ± 6.4 vs. 11.9 ± 3.1 mL/100 mL, p = 0.37 and 131 ± 50.6 vs. 132 ± 41.9 mL/beat, p = 0.76). There was a moderate positive relationship between peak oxygen consumption and peak heart rate (r = 0.67, p < 0.001), and arteriovenous oxygen difference (r = 0.59, p = 0.001). Functional capacity is significantly reduced in patients with HCM primarily due to diminished central (cardiac) rather than peripheral factors. Application of non-invasive hemodynamic assessment may improve understanding of the pathophysiology and explain mechanisms of exercise intolerance in hypertrophic cardiomyopathy.

The effect of age on mechanisms of exercise tolerance: Reduced arteriovenous oxygen difference causes lower oxygen consumption in older people.

OBJECTIVE: To assess the effect of age on mechanisms of exercise tolerance. METHODS: Prospective observational study recruited 71 healthy individuals divided into two groups according to their age i.e. younger (≤40 years of age, N = 43); and older (≥55 years of age, N = 28). All participants underwent maximal graded cardiopulmonary exercise stress testing using cycle ergometer with simultaneous non-invasive gas-exchange and central haemodynamic measurements. Using the Fick equation, arteriovenous O2 difference was calculated as the ratio between measured O2 consumption and cardiac output. RESULTS: The mean age of younger and older participants was 26.0 ± 5.7 years, and 65.1 ± 6.6 years respectively. Peak O2 consumption was significantly lower in older compared to the younger age group (18.8 ± 5.2 vs 34.4 ± 9.8 mL/kg/min, p < 0.01). Peak exercise cardiac output and cardiac index were not significantly different between the younger and older age groups (22.7 ± 5.0 vs 22.1 ± 3.9 L/min, p = 0.59; and 12.4 ± 2.9 vs 11.8 ± 1.9 L/min/m2, p = 0.29). Despite demonstrating significantly lower peak heart rate by 33 beats/min (129 ± 18.3 vs 162 ± 19.9, p < 0.01), older participants demonstrated significantly higher stroke volume and stroke volume index compared to the younger age group (173 ± 41.5 vs 142 ± 34.9 mL/min, p < 0.01; and 92.1 ± 18.1 vs 78.3 ± 19.5 mL/m2, p < 0.01). Arteriovenous O2 difference was significantly lower in older compared to younger age group participants (9.01 ± 3.0 vs 15.8 ± 4.3 mlO2/100 mL blood, p < 0.01). CONCLUSION: Ability of skeletal muscles to extract delivered oxygen represented by reduced arteriovenous O2 difference at peak exercise appears to be the key determinant of exercise tolerance in healthy older individuals.

Type A aortic dissection: Why there is still a role for echocardiography when every second counts.

Aortic dissection is often regarded as a catastrophic aortic syndrome with high rates of mortality. The sensitivity and specificity of transthoracic echocardiography when diagnosing acute type A aortic dissection has been reported as high as 97% and 100%, respectively, in patients with optimal imaging quality when compared to computed tomography. In this article, we discuss the benefit of transthoracic echocardiography in a patient with type A aortic dissection extending from ascending aorta to iliac arteries.

Impact of age on the association between cardiac high-energy phosphate metabolism and cardiac power in women.

OBJECTIVE: Diminished cardiac high-energy phosphate metabolism (phosphocreatine-to-ATP (PCr:ATP) ratio) and cardiac power with age may play an important roles in development of cardiac dysfunction and heart failure. The study defines the impact of age on PCr:ATP ratio and cardiac power and their relationship. METHODS: Thirty-five healthy women (young≤50 years, n=20; and old≥60 years, n=15) underwent cardiac MRI with 31P spectroscopy to assess PCr:ATP ratio and performed maximal graded cardiopulmonary exercise testing with simultaneous gas-exchange and central haemodynamic measurements. Peak cardiac power output, as the best measure of pumping capability and performance of the heart, was calculated as the product of peak exercise cardiac output and mean arterial blood pressure. RESULTS: PCr:ATP ratio was significantly lower in old compared with young age group (1.92±0.48 vs 2.29±0.55, p=0.03), as were peak cardiac power output (3.35±0.73 vs 4.14±0.81W, p=0.01), diastolic function (ie, early-to-late diastolic filling ratio, 1.33±0.54 vs 3.07±1.84, p<0.01) and peak exercise oxygen consumption (1382.9±255.0 vs 1940.3±434.4 mL/min, p<0.01). Further analysis revealed that PCr:ATP ratio shows a significant positive relationship with early-to-late diastolic filling ratio (r=0.46, p=0.02), peak cardiac power output (r=0.44, p=0.02) and peak oxygen consumption (r=0.51, p=0.01). CONCLUSIONS: High-energy phosphate metabolism and peak power of the heart decline with age. Significant positive relationship between PCr:ATP ratio, early-to-late diastolic filling ratio and peak cardiac power output suggests that cardiac high-energy phosphate metabolism may be an important determinant of cardiac function and performance.

Comparison of cardiac output estimates by bioreactance and inert gas rebreathing methods during cardiopulmonary exercise testing.

PURPOSE: This study assessed the agreement between cardiac output estimated by inert gas rebreathing and bioreactance methods at rest and during exercise. METHODS: Haemodynamic measurements were assessed in 20 healthy individuals (11 females, nine males; aged 32 ± 10 years) using inert gas rebreathing and bioreactance methods. Gas exchange and haemodynamic data were measured simultaneously under rest and different stages (i.e. 30, 60, 90, 120, 150 and 180 W) of progressive graded cardiopulmonary exercise stress testing using a bicycle ergometer. RESULTS: At rest, bioreactance produced significantly higher cardiac output values than inert gas rebreathing (7·8 ± 1·4 versus 6·5 ± 1·7 l min-1 , P = 0·01). At low-to-moderate exercise intensities (i.e. 30-90 W), bioreactance produced significantly higher cardiac outputs compared with rebreathing method (P<0·05). At workloads of 120 W and above, there was no significant difference in cardiac outputs between the two methods (P = 0·10). There was a strong relationship between the two methods (r = 0·82, P = 0·01). Bland-Altman analysis including rest and exercise data showed that inert gas rebreathing reported 1·95 l min-1 lower cardiac output than bioreactance, with lower and upper limits of agreement of -3·1-7·07 l min-1 . Analysis of peak exercise data showed a mean difference of 0·4 l min-1 (lower and upper limits of agreement of -4·9-5·7 l min-1 ) between both devices. CONCLUSION: Bioreactance and inert gas rebreathing methods show acceptable levels of agreement for estimating cardiac output at higher levels of metabolic demand. However, they cannot be used interchangeably due to strong disparity in results at rest and low-to-moderate exercise intensity.

Pathophysiology of exercise intolerance in chronic diseases: the role of diminished cardiac performance in mitochondrial and heart failure patients.

OBJECTIVE: Exercise intolerance is a clinical hallmark of chronic conditions. The present study determined pathophysiological mechanisms of exercise intolerance in cardiovascular, neuromuscular, and metabolic disorders. METHODS: In a prospective cross-sectional observational study 152 patients (heart failure reduced ejection fraction, n=32; stroke, n=34; mitochondrial disease, n=28; type two diabetes, n=28; and healthy controls, n=30) performed cardiopulmonary exercise testing with metabolic and haemodynamic measurements. Peak exercise O2 consumption and cardiac power output were measures of exercise tolerance and cardiac performance. RESULTS: Exercise tolerance was significantly diminished in patients compared with controls (ie, by 45% stroke, 39% mitochondria disease, and 33% diabetes and heart failure, p<0.05). Cardiac performance was only significantly reduced in heart failure (due to reduced heart rate, stroke volume, and blood pressure) and mitochondrial patients (due reduced stroke volume) compared with controls (ie, by 53% and 26%, p<0.05). Ability of skeletal muscles to extract oxygen (ie, arterial-venous O2 difference) was diminished in mitochondrial, stroke, and diabetes patients (by 24%, 22%, and 18%, p<0.05), but increased by 21% in heart failure (p<0.05) compared with controls. Cardiac output explained 65% and 51% of the variance in peak O2 consumption (p<0.01) in heart failure and mitochondrial patients, whereas arterial-venous O2 difference explained 69% (p<0.01) of variance in peak O2 consumption in diabetes, and 65% and 48% in stroke and mitochondrial patients (p<0.01). CONCLUSIONS: Different mechanisms explain exercise intolerance in patients with heart failure, mitochondrial dysfunction, stroke and diabetes. Their better understanding may improve management of patients, their stress tolerance and quality of life.

Age-related decline in cardiac autonomic function is not attenuated with increased physical activity.

Age and physical inactivity are important risk factors for cardiovascular mortality. Heart rate response to exercise (HRRE) and heart rate recovery (HRR), measures of cardiac autonomic function, are strong predictors of mortality. The present study defined the effect of age and physical activity on HRRE and HRR. Healthy women (N=72) grouped according to age (young, 20-30 years; middle, 40-50 years; and older, 65-81 years) and daily physical activity (low active <7500, high active >12,500 steps/day) performed a maximal cardiopulmonary exercise test. The HRRE was defined as an increase in heart rate from rest to 1, 3 and 5 minutes of exercise and at 1/3 of total exercise time, and HRR as the difference in heart rate between peak exercise and 1, 2, and 3 minutes later. Age was associated with a significant decline in HRRE at 1 min and 1/3 of exercise time (r=-0.27, p=0.04, and r=-0.39, p=0.02) and HRR at 2 min and 3 min (r=-0.35, p=0.01, and r=-0.31, p=0.02). There was no significant difference in HRRE and HRR between high and low-active middle-age and older women (p>0.05). Increased level of habitual physical activity level appears to have a limited effect on age-related decline in cardiac autonomic function in women.

Cu/Zn superoxide dismutase (SOD1) mutations associated with familial amyotrophic lateral sclerosis (ALS) affect cellular free radical release in the presence of oxidative stress.

INTRODUCTION: The exact molecular mechanisms by which mutations in Cu/Zn superoxide dismutase (SOD1) cause motor neuron injury remain incompletely understood, though a body of evidence suggests that the mutant protein exerts a cell-specific toxic gain of function. The role of nitric oxide (NO) in SOD1-related motor neuron injury has been particularly controversial. Theoretically, there are arguments to suggest that NO may exert an important role in motor neuron injury, but there is relatively little direct experimental support for this hypothesis. OBJECTIVES: The present study aimed to examine further the potential role for NO in motor neuron injury caused by mutant SOD1. METHOD: We have generated a cellular model of familial amyotrophic lateral sclerosis (ALS) by stably transfecting NSC34 cells with one of three mutant forms of SOD1 (G93A, G37R, I113T). In the presence of mutant SOD1, NSC34 cells show increased cell death following oxidative stress induced by serum withdrawal. This model of motor neuron death involves cellular release of superoxide and NO radicals, which were directly measured in real time using microelectrode biosensors. RESULTS: The expression of both normal and mutant SOD1 decreased the measured extracellular superoxide release, but had divergent effects on the measured release of NO. Normal SOD1 increased the measured NO release, whereas cells expressing mutant SOD1 released less NO. Co-administration of two different nitric oxide synthase inhibitors (L-NAME and L-N-methyl arginine) did show some neuroprotective effect, but this was only partial, and the effect was more marked using nuclear integrity as a measure of cell viability, rather than MTT conversion. Cells expressing mutant SOD1 were, however, more sensitive to toxicity induced by extrinsic exposure to NO, using a slow-release NO donor. CONCLUSION: NO is likely to contribute to motor neuron injury, but this does not fully account for all the cellular toxic effects of mutant SOD1.