Exercise Stress Test Research Articles

Speckle Tracking Echocardiography-Based Correlation Between Left Atrial Strain and Functional Capacity in Patients With Hypertrophic Cardiomyopathy.

The left atrium (LA) dilates and its function decreases as a chronic secondary change in hypertrophic cardiomyopathy (HCM). LA strain is a more sensitive measure of LV filling pressure than LA volume and can be used to predict the functional capacity in HCM. To analyze LA strain in patients with HCM and its correlation with exercise tolerance. A total of 113 patients with HCM were enrolled. All patients underwent detailed clinical evaluation, 24-h Holter monitoring, exercise stress testing, two-dimensional echocardiography with LA strain analysis using speckle tracking imaging. Assessment of functional capacity was done in terms of metabolic equivalents (METs). HCM patients with METS >6.0 were included in Group A while those with METS ≤6.0 were included Group B. Correlation of various parameters of LA strain (left atrial reservoir strain [LASr], left atrial conduit strain [LAScd], and left atrial contraction strain [LASct]) was done with functional capacity. The mean age of the study population was 47±10.77 years with the majority of them being males (71.9%). Group B patients had significantly lower LASr (12.95%±8.61% vs. 22.16%±16%; p<0.001), LAScd (-7.28%±6.29% vs. -12.74%±8.40%; p<0.001), and LASct (-7.44±4.46 vs. -11.19±6.53; p<0.001). Multivariable linear regression analysis reported LASr to be an independent predictor of METs and had a quadratic relationship with log-odds with negative linear and positive quadratic coefficients. LASr was the strongest echocardiographic predictor of reduced METS with an AUC of 0.78 (95% confidence interval [CI]: 0.68-0.88), sensitivity of 71.8%, and specificity of 82.9%. LA strain parameters are associated with functional capacity in patients with HCM with lower LA strain values being associated with poor functional capacity.

Evaluation of left atrial function and the relationship between left atrial stiffness index and exercise capacity in hypertension-related heart failure with preserved ejection fraction

ObjectiveThe left atrial stiffness index (LASI) holds significance in the atrioventricular coupling function and heart failure progression. To assess left atrial function and evaluate the relationship between LASI and exercise capacity in hypertension-related heart failure with preserved ejection fraction (HT-HFpEF).MethodsThe study involved 62 healthy subjects and 163 patients with HT (112 patients in simple HT group and 51 patients in HT-HFpEF group). Each patient performed exercise stress test and standard ultrasonic images were evaluated. A comprehensive evaluation of atrioventricular function, along with investigation into the correlation between these functional parameters and exercise capacity. And further to investigate the feasibility of predicting exercise intolerance using three-dimensional derived left atrial strain index (LASI) (E/e'/LASr and E/e'/LASr-c).ResultsCompared to healthy subjects, HT group demonstrated the elevation in left atrial volume accompanied by decrease in strain value (P &amp;lt; 0.05). In HT-HFpEF group, further significant reductions were observed in both longitudinal (LASr) and circumferential strain (LASr-c, LASct-c) (P &amp;lt; 0.05). Univariate regression demonstrated that both E/e'/LASr and E/e'/LASr-c were significantly correlated with metabolic equivalents (METs) (r = −0.462, P &amp;lt; 0.001; r = −0.381, P &amp;lt; 0.001). The E/e'/LASr demonstrates comparable diagnostic efficacy to exercise-E/e' in assessing exercise intolerance in HT-HFpEF patients (AUC: 0.836 vs. 0.867, P = 0.239).ConclusionProgressive LA remodeling contributes to decreased atrioventricular compliance in HT and HT-HFpEF patients.E/e'/LASr serves as an independent indicator of exercise intolerance in patients with HT-HFpEF.

Abnormal blood pressure response to exercise and ventricular arrhythmias: a suspicious association in athletes.

Abnormal blood pressure response to exercise (ABPR) in athletes is considered a risk for incident hypertension, conferring a higher cardiovascular risk profile. We sought to describe the clinical cardiovascular features of athletes with ABPR and, moreover, the relationship of ABPR with occurrence of exercise-induced ventricular ectopic beats (VEBs). We enrolled 1460 elite athletes (56.1% male; mean age 25.8 ± 5.1 years old), engaged in skills, power, mixed and endurance sport, who underwent clinical examination, transthoracic echocardiogram (TTE) and exercise stress testing. ABPR was defined as >220/85 mmHg in males and >200/80 mmHg in females. ABPR was found in 8% (n = 117) of athletes, being older (P = 0.049) and presenting higher cardiovascular risk profile (obesity, P = 0.007; glucose intolerance, P = 0.043 and familiarity for cardiovascular disease, P = 0.026). Athletes with ABPR had higher prevalence of exercise-induced VEBs (19.6% vs. 11.9% in normotensive athletes, P = 0.015). Uncommon VEBs morphology was more frequent in athletes with ABPR (64.7% vs. 19% in the normotensive, P = 0.0002). Finally, in those with ABPR and VEBs, TTE revealed greater left ventricular end-diastolic diameter indexed (P = 0-006), LVEDVi (P = 0.017) and LVMi (P = 0.04) compared to those without VEBs. A not small group of elite athletes (8%) presented an exaggerated blood pressure response to exercise and exhibited higher cardiovascular risk profile compared to their normotensive counterparts. Moreover, athletes with ABPR showed higher prevalence of ventricular arrhythmias on effort and the combination of ABPR and ventricular arrhythmias was associated with more pronounced cardiac remodelling.

Evaluating Risk Factors and the Burden of Silent Myocardial Ischemia Among Diabetic Patients.

Silent myocardial ischemia (SMI) is a significant concern for diabetic patients, often remaining undetected until severe complications arise. Prolonged hyperglycemia, poor glycemic control, and lifestyle factors contribute to its risk, with older adults and those with long-standing diabetes particularly vulnerable. To assess the prevalence and predictors of SMI in adults with diabetes, emphasizing long-term management and monitoring. A longitudinal observational study was conducted at Nishtar Medical University, Multan, from October 2020 to September 2022, involving 388 adults with diabetes for at least five years. Patients with significant cardiovascular diseases or recent medication-affecting biomarkers were excluded. Data collection included demographics, medical history, and clinical assessments such as HbA1c levels, 12-lead resting ECGs, and treadmill exercise stress tests, with myocardial perfusion imaging (MPI) for those unable to perform stress tests. Statistical analyses using IBM SPSS (version 22) incorporated univariate and multivariate logistic regression to identify predictors of SMI, adjusting for confounders such as age, sex, smoking, and blood pressure. Thresholds included microalbuminuria at 30-300 mg/24 hours and HbA1c ≥7%, with missing data addressed through multiple imputations. Among the participants, the prevalence of SMI was 48%, increasing to 58% in those with microalbuminuria. Significant predictors included the duration of diabetes (OR 1.28, 95% CI: 1.08-1.52, p=0.001), HbA1c levels (OR 1.75, 95% CI: 1.42-2.16, p<0.001), age (OR 1.05, 95% CI: 1.01-1.09, p=0.035), and smoking status (OR 1.42, 95% CI: 1.05-1.92, p=0.025). Smoking status was based on self-report. Notably, microalbuminuria showed a strong association with SMI (OR 2.89, 95% CI: 2.10-3.98, p<0.001). The distribution of participants was balanced in terms of age and gender, with a mean age of 58 years (SD 9.4), and 52% were male. No unexpected findings were observed, and the results aligned with the anticipated relationships between the variables. This study highlights a concerning prevalence of SMI among diabetic patients, emphasizing the importance of monitoring diabetes duration and glycemic control, particularly in individuals with microalbuminuria. Regular follow-up care, including routine ECGs, stress tests, and biomarker assessments, is crucial for improving cardiovascular outcomes in this high-risk population. Limitations such as the observational design and potential self-report bias in smoking status may affect the generalizability of the findings. Future research should focus on large-scale, multicenter studies to validate these findings and explore interventions that could reduce the burden of SMI in diabetic patients.

Electrocardiographic Characteristics of Brugada Syndrome Type I During Exercise Stress Test.

Brugada syndrome (BS) is a genetic channelopathy characterized by an increased risk of sudden cardiac death (SCD) in the absence of structural heart disease. Prognostic stratification is necessary to determine which patients are candidates for implantable cardioverter defibrillator (ICD). The present study aims to evaluate EKG changes during exercise stress tests in patients with BS and to identify any poor prognosis variables. This was an observational, case-control study. Three comparison groups were created: patients with Type 1 BS with or without prior arrhythmic events (BE and BNoE subgroups) and age- and sex-matched healthy individuals. Patients underwent EST and electrocardiographic variables were analyzed. The study recruited 36 patients with type 1 BS, 12 with prior Event (BE) and 24 without (BNoE). Patients in the BE group, in all postexercise recordings, had lower heart rates, notably in the first minute. A significant difference was also observed in the HR drop in the recovery phase, with a greater drop in relation to maximum HR in the first minute in the group of patients who had events. BS patients with prior events had a lower capacity to increase heart rate at peak effort and a greater proportional drop in the recovery phase. No relationship was observed between the occurrence of arrhythmic events and ST-segment elevation during the exercise test.

Abstract 4146301: Relationship Between Calf Muscle Pump Function and Exercise Stress Testing

Background: Exercise stress testing uses metabolic equivalents of tasks (METs) to measure the energy cost of activities, aiding in the assessment of exercise capacity and cardiovascular health. Despite its significance, the correlation between calf muscle pump function (CPF) and exercise stress testing remains unexplored. We aimed to evaluate the relationship between CPF and peak METs as determined by cardiopulmonary treadmill exercise stress testing. Methods: The study included adults who underwent exercise cardiopulmonary stress testing and venous plethysmography at Mayo Clinic between April 2017 and March 2020. The protocols other than Bruce, Mayo, Modified Naughton, and Naughton protocols were excluded. The CPF ejection fraction (EF) was calculated per leg based on refill volumes post-exercise as a percentage of passive drain refill. The classification of CEAP (Clinical-Etiology-Anatomy-Pathophysiology) was utilized to better understand chronic venous insufficiency (CVI). Results: A total of 155 patients who underwent both exercise stress testing and venous plethysmography were included, with a mean age of 61.31 ± 14.03 years, and 84 (54.2%) were male. The peak measured METs for normal, unilaterally reduced, and bilaterally reduced CPF were 8.5 (2.5), 7.3 (2.1), and 7.1 (2.4), respectively (p=0.004, Figure 1). Multiple linear regression models were developed with METs as the outcome to determine if CPF was an independent predictor of METs on cardiopulmonary exercise stress testing. IIn model 1, the following independent variables were included: resting heart rate, peak heart rate, peak systolic blood pressure, recovery heart rate at minute 1, and worst EF (Table 1). In model 1, with only exercise parameters, lower EF was associated with lower METs (p=0.03). In a second analysis, variables identified as statistically significant with METs in the initial model were included, along with CEAP class (model 2) and CCI (model 3) (Table 2). In model 2, CEAP class 3 or higher was associated with decreased METs on the exercise stress test. This correlation implies that individuals with moderate to severe CVI may influence exercise capacity, demonstrating the interconnectedness of the cardiovascular system. Moreover, in model 3, the CCI, a predictor for mortality, was not significantly associated with METs. Conclusion: Our findings revealed that more severe CVI (CEAP class and reduced CPF) was associated with reduced exercise capacity after accounting for other factors.

Abstract 4125701: Race and Ethnicity Are Associated with Diagnosis and Management of Wolff-Parkinson-White Pattern in Children

Background: Racial and ethnic disparities have been reported in catheter ablation in adults. There are limited data on the impact of race/ethnicity on the diagnosis and management of children with Wolff-Parkinson-White pattern (WPW). Hypothesis: Diagnosis of WPW by electrocardiogram (ECG) and risk stratification by exercise stress test (EST) and electrophysiology study (EPS) will differ by race/ethnicity in children. Methods: We performed a retrospective cohort study of patients 0-21 years old, excluding those with congenital heart disease, at a children’s hospital from 1991-2021. The primary exposure was race/ethnicity. Outcomes were 1) diagnosis of WPW on ECG, 2) undergoing EST, and 3) undergoing EPS. Likelihood and time to outcome were assessed with multivariable logistic regression adjusted for birth year and Cox regression, respectively. Results: The cohort consisted of 1,638,746 patients (White 53.0%, Black 21.0%, Hispanic 6.8%, Asian 4.2%, Multi-racial 2.0%, Other 11.0%, and Missing 1.7%). WPW was diagnosed in 898 patients (0.05%). After adjusting for birth year, Asian, Black, and Other race were associated with lower odds of WPW diagnosis compared to White patients (OR 0.57, 0.66, 0.70; p≤0.01). There was no association between race and age at first diagnosis (p=0.2). A total of 616 WPW patients (69%) underwent EST. Compared with White patients, Asian, Hispanic, and Other race were less likely to undergo EST (OR 0.39, 0.59, 0.62; p≤0.04), and those who did had their EST at later ages (HR 0.59, 0.65, 0.46; p≤0.04). A total of 739 WPW patients (82%) underwent EPS. Compared with White patients, Black, Hispanic, and Other race were less likely to undergo EPS (OR 0.44, 0.53, 0.59; p≤0.02), and those who did had their EPS at later ages (HR 0.60, 0.63, 0.66; p≤0.004). Conclusion: This analysis found that non-White racial and ethnic groups are less likely to be diagnosed with WPW. This may reflect differences in WPW prevalence by race/ethnicity, but differential access to ECG cannot be ruled out. Among WPW patients, however, Asian and Hispanic patients are approximately half as likely to undergo EST, while Black and Hispanic patients are approximately half as likely to undergo EPS, compared to White patients.

Abstract 4138424: Ring of Power: Unraveling a Rare Diagnosis in a Young Male with Palpitations

Case Description: A 36-year-old male presented for an outpatient treadmill ECG stress test for further evaluation of palpitations exacerbated by exercise. He had no ischemic ECG changes, but developed a sustained episode of polymorphic VT at 13 minutes (Figure 1a). The test was stopped and the VT self-terminated after 43 seconds. The patient was admitted for further workup. Lab workup was unremarkable; baseline ECG demonstrated no ST-T wave changes and displayed normal QT and QRS duration. TTE showed mild biventricular dysfunction. Coronary CT angiogram showed type 3 subtype of Vieussens’ arterial ring (VAR), with an absent left main and super-dominant RCA supplying both LAD and LCx. FFR-CT showed non-hemodynamically significant stenosis in the mid-distal LAD (Figure 1b). Left heart catheterization confirmed presence of VAR and mild diffuse disease in a small-caliber mid-distal LAD (Figures 1c&amp;d). No malignant course or dynamic coronary compression was present. Cardiac MRI revealed normal biventricular function and the absence of late gadolinium enhancement. An exercise stress test, now with myocardial perfusion, was performed and was entirely normal without evidence of myocardial ischemia. Genetic testing for catecholaminergic polymorphic VT was negative. After a multidisciplinary discussion, it was decided not to pursue CABG in the absence of demonstrable ischemia at peak exercise. He underwent an ICD placement for secondary prevention and was discharged on beta blockers. Discussion: Three distinct subtypes of VAR have been described, with type 3 being the rarest. The coronary anomaly was first described by Raymond de Vieussens in 1706, and represents an embryologic remnant of the conotruncal circle. It may be diagnosed incidentally in asymptomatic patients or present with angina especially if underlying CAD, aneurysms or fistulae are present. We report the first case of exercise-induced polymorphic VT in a type 3 VAR patient, theorizing that intermittent myocardial ischemia at peak exercise may induce VT in these patients. Surgical revascularization may be considered if myocardial ischemia is demonstrated on stress testing, although its benefit in patients without such evidence of ischemia is unknown.

Abstract 4132657: Age-related Differences in Peak Oxygen Uptake in Patients with Multimorbidity Undergoing Cardiac Rehabilitation

Background: Cardiac rehabilitation (CR) patients demonstrate a high burden of chronic conditions (CC). Both multimorbidity (MM; ≥2 coexisting CC) and aging negatively impact functional capacity, whereas CR improves performance. Age-related difference in cardiorespiratory fitness (CRF, peak oxygen uptake (VO 2 )) in CR patients with MM has not been studied. Hypothesis: We hypothesized improvement in CRF will be attenuated by MM with increasing age in CR patients. Aims: We aimed to identify age-related differences in CRF improvement in CR patients with MM. Methods: Patients ≥18 yrs old who attended ≥1 CR sessions from 1999-2017 and completed cardiopulmonary exercise stress test before and after CR were included. The prevalence of CC was assessed using Rochester Epidemiology Project records-linkage system. Age categories included: Younger (18-49 yrs), Midlife (50-64 yrs) and Older (≥65 yrs). CRF categories included: &lt;0%, 0-8% and &gt;8%. Analysis included Kruskal-Wallis and Chi-squared. Results: Of 622 patients, 75.4% were male. Mean age: 62.9±11.2 yrs; Younger (n=70) age: 42.7±6.8 yrs, 67.1% male; Midlife (n=283) age: 58.3±4.3 yrs, 78.8% male; Older (n=269) age: 73.0±5.2 yrs, 74.0% male. BMI was 29.9±5.4 kg/m 2 (Younger: 30.0±6.7, Midlife: 30.4±5.6, Older: 29.3±4.7; p&lt;.05). Median (Q1, Q3) no. of CR sessions attended was 33(22, 35), with lower attendance in the Younger group: 25(16,34) vs Midlife: 33(20,35) and Older: 34 (29,35), p&lt;.05. Overall, percent change in peak VO 2 was 11.5±21.6% (Younger: 18.8±22.8%, Midlife: 11.6±19.5%, Older: 9.4±23.1%; p&lt;.01). The median number of CC was 7(5,8) with significant differences across groups: Younger: 5(3,7), Midlife: 6(5,8), Older: 7(6,9), p&lt;.01. Number of CC increased with age across all CRF categories (p&lt;.01, Fig. 1). However, there was no difference in number of CC within age groups across categories of CRF, Table 1. Conclusions: Our results suggest that MM increases with age in patients attending CR; however, within a given age group, improvement in CRF does not appear dependent on MM. The impact of age appears to have a greater impact than MM on CRF improvement. Individualized treatment plans should focus on the impact of age-related disparities on CRF improvement among CR patients with MM.

Associations of the serum n-6 PUFA concentrations with exercise-induced myocardial ischaemia in middle-aged and older men.

n-6 PUFA, especially linoleic acid (LA) but also arachidonic acid (AA), have been inversely associated with CHD. However, mechanisms underlying these associations are not fully known. We investigated the associations of the serum concentrations of total n-6 PUFA, LA, AA, γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA), with the odds of myocardial ischaemia during exercise, a predictor of future cardiac events. A total of 1871 men without a history of CHD from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) aged 42-60 years were included. All participants performed a maximal symptom-limited exercise stress test, using an electrically braked bicycle ergometer. Multivariable-adjusted logistic regression was used to assess the OR for exercise-induced myocardial ischaemia in quartiles of the serum n-6 PUFA concentrations. After multivariable adjustment, men in the highest v. the lowest serum AA concentration had 50 % lower odds for exercise-induced myocardial ischaemia (OR 0·50, 95 % CI 0·34, 0·76; P-trend across quartiles < 0·001). For the other PUFA, the OR (95 % CI) were 1·00 (0·69, 1·46; P-trend = 0·89) for LA, 1·07 (0·75, 1·53; P-trend = 0·40) for GLA and 0·74 (0·51, 1·07; P-trend = 0·16) for DGLA. Among the n-6 PUFA, higher serum concentration of AA was associated with lower odds for myocardial ischaemia during an exercise test in middle-aged and older men. This may provide one mechanism for the previously observed possible cardioprotective properties of AA. Our findings also suggest that n-6 PUFA should not be considered as one homogenous group.

Effects of concentric and eccentric exercise regimens on bioenergetic efficiency of lymphocytes in sedentary males.

Eccentric exercise training (EET) increases physical performance while having lower metabolic demand than concentric exercise training (CET). Whether EET influences bioenergetic efficiency in peripheral blood mononuclear cells (PBMCs) remains unclear. This study investigates the effects of EET and CET on PBMC phenotypes and mitochondrial functions in blood. Thirty three sedentary healthy males were randomly assigned to either EET (n=11) or CET (n=11) that performed at progressively increased from 60% to 80% of maximal absolute workload for 30min/day, 5days/week for 6weeks, or a control group (n=11) that did not receive any exercise intervention. A graded exercise stress test (GXT) was performed before and after the intervention. PBMC phenotypes and mitochondrial respiratory capacity were analyzed using flowcytometry and high-resolution respirometry, respectively. In the same absolute workload, EET elicited lower heart rate and rating of perceived exertion than CET. However, EET as CET increased the VO2 level at the ventilatory threshold. Notably, both EET and CET increased central memory (CD45RO+/CD62+/CD3+) T cells and decreased effector memory T cells reexpressing CD45RA (CD45RA+/CD62-/CD3+). Moreover, the two exercise regimens diminished the loss of mitochondrial membrane potential (ΔΨm) caused by GXT, increased maximal/reserve O2 consumption rates (OCR), and bioenergetic health index in intact PBMCs and enhanced complex I-/II-related OCR in PBMCs with a substrate-rich environment. EET improves aerobic fitness with a lower cardiovascular response to exercise than CET. Moreover, EET as CET reduces senescent T-cell distribution in blood and improves PBMC bioenergetic efficiency by stabilizing ΔΨm and increasing capacity of oxidative phosphorylation.

Performance Evaluation of QT-RR Adaptation Time Lag Estimation in Exercise Stress Testing.

Slower adaptation of the QT interval to sudden changes in heart rate has been identified as a risk marker of ventricular arrhythmia. The gradual changes observed in exercise stress testing facilitates the estimation of the QT-RR adaptation time lag. The time lag estimation is based on the delay between the observed QT intervals and the QT intervals derived from the observed RR intervals using a memoryless transformation. Assuming that the two types of QT interval are corrupted with either Gaussian or Laplacian noise, the respective maximum likelihood time lag estimators are derived. Estimation performance is evaluated using an ECG simulator which models change in RR and QT intervals with a known time lag, muscle noise level, respiratory rate, and more. The accuracy of T-wave end delineation and the influence of the learning window positioning for model parameter estimation are also investigated. Using simulated datasets, the results show that the proposed approach to estimation can be applied to any changes in heart rate trend as long as the frequency content of the trend is below a certain frequency. Moreover, using a proper position of the learning window for exercise so that data compensation reduces the effect of nonstationarity, a lower mean estimation error results for a wide range of time lags. Using a clinical dataset, the Laplacian-based estimator shows a better discrimination between patients grouped according to the risk of suffering from coronary artery disease. Using simulated ECGs, the performance evaluation of the proposed method shows that the estimated time lag agrees well with the true time lag.

Sex-related differences in demographics, diagnosis and management of patients with chronic coronary syndromes.

The impact of sex-related factors on current clinical management and outcomes of chronic coronary syndromes (CCS) are unclear. All patients belonging to the prospective, nationwide START registry were included. Their baseline characteristics, diagnostic workup, revascularization strategy, pharmacological treatment and 1-year clinical outcomes were compared with respect to sex overall and in age tertiles. A total of 5070 consecutive patients were included. Most patients were males (80.1%). As expected, the prevalence of females increased with age. Distribution of risk factors and history of cardiovascular disease were different depending on sex, as well as diagnostic workup, with lower use of exercise stress testing in women (25.1% vs. 36.7%, P < 0.0001). The use of coronary angiography was similar in the two groups. Women had lower rates of multivessel coronary artery disease (CAD) (33.0% vs. 40.6% P < 0.0001) and higher rates of nonobstructive CAD (18.3% vs. 11.3%, P < 0.0001). Rates of myocardial revascularization were similar, but women were more likely to receive percutaneous coronary intervention than men (84.3% vs. 77.8%, P < 0.0001) and less likely to receive surgical/hybrid revascularization (10.0% vs. 15.1%, P < 0.0001). At 12-month follow-up, no differences were observed for the combined endpoint of all-cause mortality, re-hospitalization for myocardial infarction, heart failure, stroke or myocardial revascularization between males and females; however, a significantly worse perceived quality of life was observed in women. In a large nationwide cohort of patients with CCS, clinical outcomes were not different depending on sex. However, several differences in the diagnostic work-up, treatment strategies and quality of life were found between sexes.

From the armchair to contemporary cardiac rehabilitation: the remarkable ongoing journey of exercise training in ischemic heart disease.

Exercise is an important physiological activity with several health benefits. In the setting of ischemic heart disease (IHD), the view toward exercise has greatly evolved throughout the years, concurrently to several major advances in the management of this complex entity. Currently, exercise training has broad applications across the IHD continuum as a powerful tool in its overall management, being a core component of comprehensive cardiac rehabilitation programs. Beyond this, exercise has also been incorporated as an integral part of contemporary methodologies aiming to provide diagnostic and prognostic data, such as cardiopulmonary exercise stress testing or stress echocardiography. In this article, we provide a pragmatic overview concerning the role of exercise in IHD, with a focus on its incorporation in cardiac rehabilitation frameworks, while also discussing some of the challenges and unmet needs concerning these interventions.

Predicting physical fitness levels from resting ECG data: a machine learning approach in cardiovascular assessment

Abstract Background Exercise Stress Testing (EST), an inexpensive noninvasive modality, is widely used for preliminary cardiovascular evaluation and ongoing monitoring of cardiac patients. The MET (Metabolic Equivalent of Task) score from EST, indicating physical fitness, is associated with overall mortality risk and is extremely helpful for preoperative evaluation. Artificial Intelligence (AI) advances, particularly Deep Learning (DL) for resting ECG analysis, have significantly improved cardiac diagnostic accuracy. Objectives This study explores AI's ability to predict MET scores from resting ECGs, aiming to streamline fitness assessments and detect early changes in fitness levels. Methods The current analysis encompasses 45,518 consecutive EST evaluations from 31,532 individual patients from 2017 to 2023. MET scores were automatically computed using an established formula, while interpretations by certified cardiologists provided a benchmark for the AI model. Poor fitness was defined as being within the lowest quartile of MET scores, adjusted for sex and age. A deep learning framework was developed to process a 10-second snippet of resting phase ECG in raw waveform, predicting the likelihood of diminished fitness and thus acting as a binary classifier. The efficacy of this Poor Fitness AI model (PF-AI model) was assessed through metrics such as the area under the receiver operating characteristic curve (AUROC), along with sensitivity, specificity, and accuracy rates. Results The average age of the study group was 55±10 years, predominantly male (68.8%, n = 31,337). Among them, 1,152 were identified as having poor fitness. Applying the model to the entire cohort through 5-fold cross-validation yielded a sensitivity of 78%, a specificity of 81%, and an AUROC of 0.87 in predicting poor fitness. Conclusions Leveraging merely 10 seconds of resting ECG data, the PF-AI model proves to be a robust tool in predicting poor fitness levels, comparable to the outcomes of comprehensive stress testing.

LCoRL Regulates Growth and Metabolism.

Genome-wide association studies (GWAS) in humans and livestock have identified genes associated with metabolic traits. However, the causality of many of these genes on metabolic homeostasis is largely unclear due to a lack of detailed functional analyses. Here we report ligand-dependent corepressor-like (LCoRL) as a metabolic regulator for body weight and glucose homeostasis. Although GWAS data show that LCoRL is strongly associated with body size, glucose homeostasis, and other metabolic traits in humans and livestock, functional investigations had not been performed. We generated Lcorl knockout mice (Lcorl-/-) and characterized the metabolic traits. We found that Lcorl-/- pups are born smaller than the wild-type (WT) littermates before reaching normal weight by 7 to 9 weeks of age. While aging, Lcorl-/- mice remain lean compared to WT mice, which is associated with a decrease in daily food intake. Glucose tolerance and insulin sensitivity are improved in Lcorl-/- mice. Mechanistically, this stunted growth is linked to a reduction of circulating levels of IGF-1. The expression of the genes downstream of GH signaling and the genes involved in glucose and lipid metabolism are altered in the liver of Lcorl-/- mice. Furthermore, Lcorl-/- mice are protected against a high-fat diet challenge and show reduced exercise capacity in an exercise stress test. Collectively, our results are congruent with many of the metabolic parameters linked to the Lcorl locus as reported in GWAS in humans and livestock.

Machine learning and traditional analysis of the interaction between cardiovascular diseases and hematological malignancies

Abstract Background Cardiovascular diseases and clonal hematopoiesis of indetermine potential (CHIP), the premalignant state of hematological cancers, exhibit reciprocal interactions. While the presence of CHIP confer a risk for heart failure, it is unclear if cardiovascular diseases are associated with elevated risk hematological cancers. Purpose To determine the association between cardiovascular diseases (CVD) and cardiovascular risk, and hematological cancer. Methods We evaluated 27,231 adults, free of CVD and cancer, who participated in preventive healthcare program between 2000-2018. Each participant underwent a complete physical evaluation, blood test and exercise stress test at baseline. CVD was defines as ischemic heart disease, stroke, atrial fibrillation or hypertension. Then, we used machine learning and traditional survival analysis to evaluate the association between CVD and hematological cancer. For machine learning, we used the random forest method using Curat package in r, and incorporated all continuous variables gathered into the model (70% training, 30% test). For survival analysis, we first matches each CVD patient to a control patient by propensity scores to balance for age, sex, smoking, diabeles mellitus, renal function, body mass index and length of follow-up. Then, we compared the CVD and non-CVD patients using cox proportional hazard regression. Results Using machine learning, we found that the strongest predictors for hematological cancer in our cohort are low eGFR, age, high atherosclerosis cardiovascular disease score (ASCVD) and BMI. Of note, systolic and diastolic blood pressure were also strong predictors of hematological cancer (Figure A). Then, we matched 5500 CVD patients to controls with median follow-up of 9.2 years (Interquartile range 5-15 years). During follow-up, 1380 developed cancer. Of them, 186 developed hematological cancer. We used cox proportional hazard regression and Kaplan Mayer method to determine the risk and hazard ratio of developing hematological cancer (Figure B-C). Compared with subjected without CVD, patients with CVD were 91% more likely to develop cancer during follow-up, and 62% more likely to develop hematological cancer (Figure C, HR=1.61. 95%CI 1.21-2.16). Moreover, the 10-year risk to develop hematological cancer was 1.9% for patients with CVD and 1.0% for individuals without CVD (Figure D). Notably, the increased incidence of hematological cancers included 38% increase in cases of leukemia but only 11% increase in cases of lymphoma. Conclusions Using machine learning and traditional analysis we show that CVD risk and CVD were associated with increased incidence of hematological cancer. Understanding this relationship could lead to advances in cardiovascular and cancer treatment and could ultimately help to improve patient outcomes.

The association between exercise-induced ventricular premature contractions and long-term mortality in patients without coronary artery disease

Abstract Background/Introduction The treadmill exercise test is widely used clinical test to determine cardiovascular risk and mortality, regardless of clinical risk factors (1). ST-segment changes detected in the exercise test are shown to predict myocardial ischemia (2) and premature ventricular complexes (PVCs) are frequently observed during exercise stress testing (3). Exercise-related PVC is observed in 14% to 23% of healthy individuals without significant heart disease (4,5). The literature on the role of PVCs observed during treadmill exercise testing in predicting prognosis is controversial. Purpose Therefore, we aimed to evaluate the clinical results of PVCs seen during exercise testing in patients who had been diagnosed with non-obstructive coronary artery disease after coronary angiography. Methods The study population consisted of 1624 consecutive patients who were considered high risk according to the Duke treadmill risk score and had no significant stenosis on coronary angiogram from January 2016 to April 2021. Patients with previous history of coronary revascularization, previous myocardial infraction, heart failure, moderate or severe heart valve disease, congenital heart disease, cardiomyopathy, bundle branch block, and left ventricular hypertrophy were excluded from the study. The primary endpoints of the study were long-term all-cause mortality of patients who had PVCs during the exercise test or during the resting phase. Results The long-term mortality was observed in 53 patients out of 1624 patients in the mean follow-up of 47 months. PVCs was observed in 293 (18.7%) patients without long-term mortality, while PVCs was observed in 24 (45.3%) patients with long-term mortality (p&amp;lt;0.001). The model adjusted for all covariates showed that the presence of PVCs in the recovery phase (p&amp;lt;0.007, HR (95% CI) 2.244 (1.244 – 4.047)) and advanced age (p&amp;lt;0.001, HR (95% CI) 1.194 (1.143 – 1.247)) were associated with long-term all-cause mortality (Figure 1). Considering Kaplan-Meier curve, individuals with PVCs in recovery had significantly higher risk of long-term mortality compared with those with without PVCs (log-rank statistic: 22.47, p&amp;lt;0.001) (Figure 2). Conclusion(s) The study highlights that PVCs monitored in the recovery phase of the treadmill exercise test were associated with long -term mortality in patients without structural heart disease and coronary artery disease.Figure 2Figure 1

Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) measurement in the detection of significant CAD in acute chest pain patients triaged using the No Objective Testing (NOT) rule

Abstract Background After rule-out of MI in ED chest pain patients, uncertainty exists with respect to which remaining patients would benefit from objective functional/anatomical testing to detect potential underlying CAD. Using proteomics, we experimentally identified IGFBP-3 as a biomarker to assist this risk stratification and applied its measurement to &amp;gt;3,000 ED patients from 3 separate studies. Methods An isolated rat heart perfusate model coupled to mass spectrometry identified markers of cardiac ischemia. Human cardiac ischemia was carried out using cardiac exercise stress testing (EST, n=12). Temporal changes in IGFBP-3 during experimental MI were determined in patients undergoing septal alcohol ablation (SAA, n=12) and arterio-venous gradients of IGFBP-3 were determined from cases of proscribed cardiac catheterisation (CC, n=14). The ability of IGFBP-3 to assist clinical assessment (ROC analyses, logistic regression, C-statistic, pathways analyses) and ED risk assessment by the No Objective Testing (NOT) rule was carried out on samples from 3 prospectively recruited studies (SPACE, NZ, n=766; APACE, CH, n=1,056; FAST-TRAC, USA, n=1,230). Results IGFBP-3 identified by MS was present in perfusates of ischemic hearts only (n=3). In human cardiac EST, a delta of IGFBP-3 (∆IGFBP-3) between 0-150minutes was seen in positive ischemic tests, but not in controls (n=6 per group, p=0.026). In SAA patients, peripheral IGFBP-3 levels did not change over 24 hours (n=12, p=0.573) whereas in CC patients, significant extraction gradients of IGFBP-3 were seen across the heart and liver (p=0.013, n=14). In ED chest pain patients identified by the NOT rule (n=1,708), ΔIGFBP-3 between presentation and +2 hours (∆ IGFBP-3) was an independent logistic model predictor of unstable angina (n=123) alongside age, sex, cholesterol and Hx of CAD/MI. At 90% specificity, ∆IGFBP-3 improved the sensitivity of the model from 31% to 43%, the PPV 20% to 25% and the NPV from 94% to 95% (p=0.020). IGFBP-3 made a small improvement in "low risk" NOT rule patient identification (29% to 30%), but made a larger improvement to the ROC curve based identification in NOT rule patients for the finding of stenosis &amp;gt;70% on angiography (n=101, AUC clinical model = 0.682; model plus ∆ IGFBP-3 = 0.725, p=0.044). Pathways analyses (that included hs-TnT) in angiography patients (n=224) revealed ∆IGFBP-3 generated a 28% relative increase in low risk case identification (n=46 to 59). Conclusions IGFBP-3 is identified as a novel potential biomarker of cardiac ischemia, that is taken up/degraded across the heart and appears less responsive to complete infarction (MI). 0-2 hour changes in IGFBP-3 (∆ IGFBP-3) in patients identified as eligible for ED based NOT rule inclusion show promise as a useful tool to identify those with significant CAD, evidenced by the diagnosis of unstable angina, positive EST results or findings of 70% occlusion on angiography.

Exercise stress testing recovery kinetics: the forgotten phase

Abstract Background Impaired exercise capacity is a cardinal feature of heart failure (HF). Peak oxygen uptake (pVO2) and ventilatory efficiency (VE/VCO2 slope) during exercise are well-consolidated prognostic markers in patients with HF. A previous study suggested that abnormally prolonged VO2 recovery, specifically the failure to decrease VO2 from peak exercise by 10.5 mL/kg/min at 180 seconds of the recovery phase, predicts adverse outcomes in HF. However, it is unknown to what extent the recovery of VEqCO2, a marker of ventilation/perfusion mismatch, adds prognostic value to the already existing parameters. Purpose The aim of this study was to characterize the functional and prognostic significance of VEqCO2 kinetics following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (&amp;gt;3 months) and stable HF with left ventricular ejection fraction (LVEF) &amp;lt;50% who underwent cardiopulmonary exercise testing (CPET) between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sittng passively for 2 minutes). VO2 and VEqCO2 kinetics during recovery, described as the absolute difference to peak VO2 (difVO2) and VEqCO2 (difVEqCO2), were measured at 30, 60, 120, and 180 seconds. Outcomes were assessed as a composite of cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) implantation at 1 year. Results A total of 238 patients were included (mean age 58 ± 12 years; 82% males; mean LVEF 34 ± 10%; 68% with ischemic HF; 75% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean VE/VCO2 slope 41 ± 12). During the 1-year follow-up, 19 patients met the endpoint (8 CV deaths, 8 urgent heart transplants, and 3 LVAD). ROC curve analysis showed that the best correlation between difVEqCO2 and outcomes was apparent at difVEqCO2 of 180 seconds (AUC 0.83) with a cut-off value of 1 (sensitivity 93%, specificity 58%). These patients, who had a decrease in VEqCO2 (difVEqCO2 &amp;gt;1) at 180 seconds, were significantly older (p=0.02), had a lower LVEF (p&amp;lt;0.001), and higher NYHA (p&amp;lt;0.001). They were at an increased risk of cardiovascular events compared to those with an increase in VEqCO2 (difVEqCO2 &amp;lt;1) at 180 seconds (event-free survival at 1 year 86% vs. 98%, log-rank p&amp;lt;0.001). In multivariate analysis, the statistical association between difVEqCO2 and outcomes remained significant, even after adjusting for difVO2 at 180 seconds (HR 4.315, CI95% (1.349-13.804), p=0.014). Conclusion Abnormal VEqCO2 kinetics in the recovery period of CPET is an easily recognizable non-invasively derived measurement that predicts outcomes in HF. VEqCO2 may complement the evaluation of VO2 and other parameters during recovery to further improve prognostic risk stratification in HF.