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.

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.

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.

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.