Shortness of breath in clinical practice: A case for left atrial function and exercise stress testing for a comprehensive diastolic heart failure workup

The symptom cluster of shortness of breath(SOB) contributes significantly to the outpatient workload of cardiology services. The workup of these patients includes blood chemistry and biomarkers, imaging and functional testing of the heart and lungs. A diagnosis of diastolic heart failure is inferred through the exclusion of systolic abnormalities, a normal pulmonary function test and normal hemoglobin, coupled with diastolic abnormalities on echocardiography. Differentiating confounders such as obesity or deconditioning in a patient with diastolic abnormalities is difficult. While the most recent guidelines provide more avenues for diagnosis, such as incorporating the left atrial size, little emphasis is given to understanding left atrial function, which contributes to at least 25% of diastolic left ventricular filling; additionally, exercise stress testing to elicit symptoms and test the dynamics of diastolic parameters, especially when access to the "gold standard" invasive tests is lacking, presents clinical translational gaps. It is thus important in diastolic heart failure work up to understand left atrial mechanics and the role of exercise testing to build a comprehensive argument for the diagnosis of diastolic heart failure in a patient presenting with SOB.

Exercise stress echocardiography:Where are we now?

Exercise stress echocardiography(ESE)is a widely used diagnostic test in cardiology departments.ESE is mainly used to study patients with coronary artery disease;however,it has increasingly been used in other clinical scenarios including valve pathology,congenital heart disease,hypertrophic and dilated cardiomyopathies,athlete evaluations,diastolic function evaluation,and pulmonary circulation study.In our laboratories,we use an established methodology in which cardiac function is evaluated while exercising on a treadmill.After completing the exercise regimen,patients remain in a standing position or lie down on the left lateral decubitus,depending on the clinical questions to be answered for further evaluation.This method increases the quality and quantity of information obtained.Here,we present the various methods of exercise stress echocardiography and our experience in many clinical arenas in detail.We also present alternatives to ESE that may be used and their advantages and disadvantages.We review recent advances in ESE and future directions for this established method in the study of cardiac patients and underline the advantage of using a diagnostic tool that is radiation-free.

Autonomic Function in Individuals with Slow Heart Rate Response following an Exercise Stress Test

Objective: To examine the autonomic function using HRV measures in apparently healthy individuals undergoing exercise stress test (EST) and demonstrating slow HRR response. Methods: HRV was measured with 12 lead ECGs during graded EST and analyzed via a post-processing method. Autonomic function was determined by Power Spectral Analysis of the very low frequency (VLF), low frequency (LF), high frequency (HF), and the ratio of LF/HF. We correlated HRV indices with resting, exercise, and recovery data. Results: No differences were found in anthropometric measurements, peak EST HR, and METS between individuals with slow HRR (below 18 b/min) compared with controls (HRR > 18 b/min). Only the VLF component of the HRV indices was statistically different (p = 0.03) at one-minute post-exercise compared with controls. Additionally, a significant correlation between HRR and resting LF and HF indices was found in the individuals with slow HRR but not in the controls. Conclusion: In apparently healthy individuals with slow HRR post-EST, autonomic function did not demonstrate any differences at any phase of the EST, including at one minute of recovery. However, a significant correlation was found between resting LF and HF powers and HRR in individuals with slow vagal reactivation post-exercise. The clinical and prognostic implications of such observation deserve further investigation.

Heart rate response and recovery during exercise predict future delirium risk——A prospective cohort study in middle-to older-aged adults

Background:Delirium is a neurocognitive disorder characterized by an abrupt decline in attention,awareness,and cognition after surgical/illness-induced stressors on the brain.There is now an increasing focus on how cardiovascular health interacts with neurocognitive disorders given their overlapping risk factors and links to subsequent dementia and mortality.One common indicator for cardiovascular health is the heart rate response/recovery(HRR)to exercise,but how this relates to future delirium is unknown.Methods:Electrocardiogram data were examined in 38,740 middle-to older-aged UK Biobank participants(mean age=58.1 years,range:40-72 years;47.3%males)who completed a standardized submaximal exercise stress test(15-s baseline,6-min exercise,and 1-min recovery)and required hospitalization during follow-up.An HRR index was derived as the product of the heart rate(HR)responses during exercise(peak/resting HRs)and recovery(peak/recovery HRs)and categorized into low/average/high groups as the bottom quartile/middle 2 quartiles/top quartile,respectively.Associations between 3 HRR groups and new-onset delirium were investigated using Cox proportional hazards models and a2-year landmark analysis to minimize reverse causation.Sociodemographic factors,lifestyle factors/physical activity,cardiovascular risk,comorbidities,cognition,and maximal workload achieved were included as covariates.Results:During a median follow-up period of 11 years,348 participants(9/1000)newly developed delirium.Compared with the high HRR group(16/1000),the risk for delirium was almost doubled in those with low HRR(hazard ratio=1.90,95%)confidence interval(95%CI):1.30-2.79,p=0.001)and average HRR(hazard ratio=1.54,95%CI:1.07-2.22,p=0.020)).Low HRR was equivalent to being 6 years older,a current smoker,or>3 additional cardiovascular disease risks.Results were robust in sensitivity analysis,but the risk appeared larger in those with better cognition and when only postoperative delirium was considered(n=147;hazard ratio=2.66,95%CI:1.46-4.85,p=0.001).Conclusion:HRR during submaximal exercise is associated with future risk for delirium.Given that HRR is potentially modifiable,it may prove useful for neurological risk stratification alongside traditional cardiovascular risk factors.

Relationship between exercise induced elevation of left ventricular filling pressure and exercise intolerance in patients with atrial fibrillation

Background Elevated left ventricular filling pressure （LVFP） is an important cause of exercise intolerance in patients with atrial fib- dilation （AF）. Exercise stress echocardiography could assess LVFP during exercise. The objective of this study was to investigate the relationship between exercise induced elevation of LVFP and exercise capacity in patients with AF. Methods This study included 145 con- secutive patients （81 men and 64 women; mean age 65.5 ± 8.0 years） with persistent non-valvular AF and normal left ventricular systolic function （left ventdcular ejection fraction 〉 50%）. All patients underwent a symptom-limited cardiopulmonary exercise test （CPET）. Doppler echocardiography was performed both at rest and immediately after exercise. Five consecutive measurements of early diastolic mitral inflow velocity （E） and early diastolic mitral annular velocity （e＇） were taken and averaged. E/e＇ ratio was calculated. Elevated LVFP was defined as E/e＇ 〉 9, and patients with elevated LVFP at rest were excluded. Results Patients were classified into two groups according to LVFP estimated by E/e＇ ratio after exercise： 39 （26.9%） with elevated LVFP after exercise and 106 （73.1%） with normal LVFP. As compared with patients with normal LVFP, the ones with elevated LVFP after exercise had significantly lower peak oxygen uptake （VO2 peak） （21.7 ± 2.3 vs. 26.4 ± 3.8 mL/min per kilogram, P 〈 0.001）, lower anaerobic threshold （19.9 ± 2.5 vs. 26.0± 4.0 mL/min per kilogram, P 〈 0.001）, and shorter exercise time duration （6.2± 0.8 vs. 7.0 ±1.3 min, P 〈 0.001）. Multivariate analysis showed that age, gender and E/e＇ after exercise were significantly correlated with VO2peak. Conclusion Elevated LVFP estimated by E/e＇ ratio after exercise is independently associated with reduced exercise capacity in AF patients.

The effects of sotalol on ventricular repolarization during exercise

Objective: Although after pacing animal and human studies have demonstrated a rate-dependent effect of sotalol on ventricular repolarization, there is little information on the effects of sotalol on ventricular repolarization during exercise. This study attempted to show the effects of sotalol on ventricular repolarization during physiological exercise. Methods: Thirty-one healthy volunteers (18 males, 13 females) were enrolled in the study. Each performed a maximal treadmill exercise test according to the Bruce protocol after random treatment with sotalol, propranolol and placebo. Results: Sotalol significantly prolonged QTc (corrected QT) and JTc (corrected JT) intervals at rest compared with propranolol (QTc 324.86 ms vs 305.21 ms, P<0.001; JTc 245.04 ms vs 224.17 ms, P<0.001) and placebo (QTc 324.86 ms vs 314.06 ms, P<0.01; JTc 245.04 ms vs. 232.69 ms, P<0.001). The JTc percent reduction increased progressively with each stage of exercise and correlated positively with exercise heart rate (r=0.148, P<0.01). The JTc percent reduction correlation with exercise heart rate did not exist with either propranolol or placebo. Conclusions: These results imply that with sotalol ventricular repolarization is progressively shortened after exercise. Thus the specific class III antiarrhythmic activity of sotalol, present as delay of ventricular repolarization, may be attenuated during exercise. Such findings may imply the need to consider other antiarrythmic therapy during periods of stress-induced tachycardia.

Beneficial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease

BACKGROUND：Non-alcoholic fatty liver disease（NAFLD）refers to any fatty liver disease that is not due to excessive use of alcohol.NAFLD probably results from abnormal hepatic lipid metabolism and insulin resistance.Aerobic exercise is shown to improve NAFLD.This review aimed to evaluate the molecular mechanisms involved in the beneficial effects of aerobic exercise on NAFLD.DATA SOURCE：We searched articles in English on the role of aerobic exercise in NAFLD therapy in Pub Med.RESULTS： The mechanisms of chronic aerobic exercise in regulating the outcome of NAFLD include： （i） reducing in- trahepatic fat content by down-regulating sterol regulatory element-binding protein-lc and up-regulating peroxisome proliferator-activated receptor y expression levels; （ii） decreas- ing hepatic oxidative stress through modulating the reactive oxygen species, and enhancing antioxidant enzymes such as catalase and glutathione peroxidase; （iii） ameliorating hepatic inflammation via the inhibition of pro-inflammatory media- tors such as tumor necrosis factor-alpha and interleukin-1 beta; （iv） attenuating mitochondrial dependent apoptosis by reducing cytochrome C released from the mitochondria to the cytosol; and （v） inducing hepato-protective autophagy. CONCLUSION： Aerobic exercise, via different mechanisms, significantly decreases the fat content of the liver and improves the outcomes of patients with NAFLD.

Reproducibility of Heart Rate Recovery in Individuals with Low Heart Rate Recovery Response

Objective: To examine the reproducibility of HRR in healthy individuals with slow HRR response undergoing routine annual checkups. Method: HRR data (>18 b/min;Group 1 and 18 b/min;Group 2) were analyzed using a fixed-effects regression model adjusted for age and gender, including random effects group-specific slopes on age. Results: One hundred and thirteen individuals (56.5 ± 9.2 y), underwent 573 cumulative ESTs with an average of 5.1 ± 1.6 tests per individual during a 21-year retrospective follow-up. No differences were found in anthropometric measurements and blood variables. All individuals achieved 94% ± 7.7% of age-predicted HR max at peak EST. Group 2 demonstrated 38% of inconsistent HRR. Regression analysis demonstrated a decrease of 0.5 b/min, on average across individuals, in HRR per each extra year of age. The random effects showed an inter-subject SD level of 9.91 b/min and an SD on the age slope of 0.40 b/min/year. Conclusion: HRR showed low reproducibility in nearly 40% of tests, which was not reflected by the variation of HR nor in the slope of age during a 21-year retrospective follow-up.

Diet Guidelines Stress Exercise for First Time

美国有一个每四年公布一次的dietary guidelines(食品指导),它被誉为gold standard of nutritional information。今年修正的dietary guidelines增加了新的exercise的内容,非常引人注目:The new guideliner recommend that bothadults and children get at least 30 minutes of physical activity daily in order tolower the risk of heart disease,colon(结肠)cancer and diabetes(糖尿病;多尿症).本文最幽默的一句话是:Although you don’t eat exercise,it’s the second half ofthe energy balance equation.(虽然你不吃“运动”,可是,运动却是能量收支平衡的另一部分。)此话非常形象地道出了运动的重要性。本文强调了所谓healthyliving,每日的饮食应该是:We should choose more whole-grain foods and a varietyof fruits and vegetables every day.美国总统克林顿亲自公布了这个新的食品指导,报道还顺便透露了总统本人的一些“隐私”,读来让人颇生联想: 1/…who(指克林顿)has a well-documented(被证明了的)appetite for not-very-healthy food. 2/Clinton,a regular jogger(慢跑者)until a knee injury in 1997.本文的另一个重要信息是:少吃糖！…the final version calls for Americans to

Value of cardiovascular interaction by exercise echocardiography according to gender

Background The cardiovascular interaction is important for the heart to achieve maximal cardiac work.The cardiovascular stiffness contributes to exercise intolerance. However, the difference in cardiovascular stiff-ness between genders is seldom reported when the objects do exercise. This study was to evaluate the ventricu-lar and arterial stiffness at rest and exercise according to gender. Methods Forty healthy volunteers were studied. The left ventricular function, structure and blood flow were measured by echocardiograph at rest and exercise. The derived variables including left ventricular end-systolic and diastolic elastance（Ees and Ed）, arterial elastance（Ea）, ventricular-vascular coupling index（VVI） and total stiffness index（TSI） were calculated.Results During exercise, all of the Ed, Ees, Ea and TSI showed significant increase, but VVI was no difference compared with them at rest. Both at rest and exercise, Ed, VVI and TSI had significantly higher in women than in men. The area under the receiver operating characteristic curves showed the area of Ed, Ees, Ea and TSI was greater than that of VVI. There were significant differences in Ed, Ees, Ea and TSI（P 〈 0.05）, but no significant difference in VVI（P 〉 0.05） between rest and exercise. Only in women, the Ed, Ees and Ea were correlated with the TSI, rate pressure product, E/e and EF. Conclusions Exercise leads to synchronous increase in ventricular and arterial stiffness, and ventriculoarterial coupling is maintained for healthy objects. The exercise intolerance is lower in women than in men.