Cardiopulmonary Stress Testing Research Articles

Hemodynamic determinants of left atrial strain in patients with hypertrophic cardiomyopathy: A combined echocardiography and CMR study.

BackgroundLeft atrial (LA) strain is associated with symptomatic status and atrial fibrillation in patients with hypertrophic cardiomyopathy (HCM). However, hemodynamic determinants of LA reservoir (LARS), conduit, and pump strains have not been examined and data are needed on the relation of LA strain with exercise tolerance in HCM.MethodsFifty HCM patients with echocardiographic and CMR imaging within 30 days were included. Left ventricular (LV) volumes, mass, EF, scar extent, extracellular volume fraction (ECV), and LA maximum volume were measured by CMR. Echo studies were analyzed for mitral inflow, pulmonary vein flow, mitral annulus tissue Doppler velocities, LV global longitudinal strain, and LA strain. Twenty six patients able and willing to exercise underwent cardiopulmonary stress testing for peak oxygen consumption (MVO2), and VE/VCO2 slope. Patients were followed for clinical events.FindingsLARS was significantly associated with indices of LA systolic function, LV GLS, and LV filling pressures (P<0.05). Conduit strain was significantly associated with mitral annulus early diastolic velocity and ECV, whereas LA pump strain was determined by LA systolic function and indices of LV end diastolic pressure (all P<0.05). LARS and conduit strain were significantly higher in patients who achieved ≥80% of MVO2. LARS, conduit, and pump strains were significantly associated with atrial fibrillation (P<0.05).ConclusionsLV structure, systolic and diastolic function, and LA systolic function determine the 3 components of LA strain. LA strain is associated with exercise tolerance and clinical events in patients with HCM.

Predicting heart failure transition and progression: a weighted risk score from bio-humoral, cardiopulmonary and echocardiographic stress testing

Abstract Funding Acknowledgements Type of funding sources: None. Aims. We tested the prognostic role of a risk score including bio-humoral evaluation, cardiopulmonary-echocardiographic stress (CPET-ESE) and lung ultrasound, in patients with heart failure (HF) with reduced and preserved ejection fraction (HFrEF and HFpEF), and subjects at risk of developing HF (American College of Cardiology/American Heart Association Stages A and B). Methods and results. We evaluated 318 subjects: 94 in Stages A-B, 194 in Stage C (85 HFpEF and 109 HFrEF), and 30 age and sex-matched controls (Stage 0). During a median follow-up of 18.5 months, we reported 40 urgent HF visits, 31 HF hospitalisations and 10 cardiovascular deaths. Cox proportional-hazards regression for predicting adverse events identified five independent predictors and each was assigned a number of points proportional to its regression coefficient: Δstress-rest B-lines &amp;gt;10 (3 points), peak oxygen consumption &amp;lt;16 mL/kg/min (2 points), minute ventilation/carbon dioxide production slope ≥36 (2 points), peak systolic pulmonary artery pressure ≥50 mmHg (1 point) and resting N-terminal pro-brain natriuretic peptide (NT-proBNP) &amp;gt;900 pg/mL (1 point). We defined three risk categories: low-risk (&amp;lt;3 points), intermediate-risk (3-6 points), and high-risk (&amp;gt;6 points). The event-free survival probability for these three groups were 93%, 52% and 20%, respectively. Hazard Ratio was 4.55 for each risk category upgrade (95% confidence interval [CI], 3.44-5.93). The area-under-curve for the scoring system to predict events was 0.92 (95% CI 0.88-0.96). Conclusion. A multiparametric risk score including indices of exercise-induced pulmonary congestion, markers of cardiopulmonary dysfunction and NT-proBNP identifies patients at increased risk for HF events across the HF spectrum. Table 1 Variable EPYC score EPYC score &amp;lt;3 (low risk) n = 217 EPYC score 3-6 (intermediate risk) n = 70 EPYC score &amp;gt;6 (high risk) n = 31 p-value (between risk categories) Event-free (n = 244) 0 (0 - 2) 210 (97) 32 (46) 2 (6) &amp;lt;0.0001 With events (n = 74) 6 (4 - 9) 7 (3) 38 (54) 29 (94) &amp;lt;0.0001 p-value (event-free vs with events) &amp;lt;0.0001 &amp;lt;0.0001 &amp;lt;0.0001 &amp;lt;0.0001 Stage 0-Controls (n = 30) 0 (0 - 1) 30 0 0 &amp;lt;0.0001 Stages A-B (n = 94) 1 (0 - 2) 85 (45) 6 (9) 3 (10) &amp;lt;0.0001 Stage C-HFpEF (n = 85) 3 (1 - 6)*† 46 (25) 29 (41) 10 (32) &amp;lt;0.0001 Stage C-HFrEF (n = 109) 4 (2 - 7)*† 56 (30) 35 (50) 18 (58) &amp;lt;0.0001 p-value (between HF Stages) &amp;lt;0.0001 &amp;lt;0.0001 &amp;lt;0.0001 &amp;lt;0.0001 Values are mean ± standard deviation, n (%), or median [25th quartile, 75th quartile]. * p &amp;lt; 0.01 vs Stage 0-Controls; † p &amp;lt; 0.01 vs Stages A-B. Abstract Figure 1

Cardiac reserve and exercise capacity: insights from combined cardiopulmonary and exercise echocardiography stress testing

Abstract Funding Acknowledgements Type of funding sources: None. Aims. Combined cardiopulmonary exercise test (CPET) and exercise stress echocardiography (ESE) provides a non-invasive tool to study cardiopulmonary pathophysiology. We analyzed how cardiac functional reserve during exercise relates to peak oxygen consumption (VO2). Methods and Results. We performed a symptom-limited graded ramp bicycle CPET-ESE in 30 healthy controls and 357 patients: 113 at risk of developing heart failure (American College of Cardiology/American Heart Association HF Stages A-B) and 244 in HF Stage C with preserved (HFpEF, n = 101) or reduced ejection fraction (HFrEF, n = 143). Peak VO2 significantly decreased from controls to Stage A-B and Stage C (Table 1). A multivariable regression model to predict peak VO2 revealed peak left ventricular systolic annulus tissue velocity (S"), peak TAPSE/PAPs (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) and low-load left atrial reservoir strain/E/e’ were independent predictors, in addition to peak heart rate, stroke volume and workload (adjusted R²=0.76, p &amp;lt; 0.0001). The model was successfully tested in subjects with atrial fibrillation (n = 49), and with (n = 224) and without (n = 163) beta-blockers (all p &amp;lt; 0.01). Peak S’ showed the highest accuracy in predicting peak VO2 &amp;lt; 10 mL/kg/min (cut-point ≤ 7.5 cm/s; AUC = 0.92, p &amp;lt; 0.0001) and peak VO2 &amp;gt; 20 mL/kg/min (cut-point &amp;gt; 12.5 cm/s; AUC = 0.84, p &amp;lt; 0.0001) in comparison to the other cardiac variables of the model (p &amp;lt; 0.05). Conclusions. A model incorporating different measures of cardiac mechanics is strongly related to peak aerobic capacity and may help in identifying different causes of effort intolerance from HF Stage A to C. Table 1 Variable Overall population (n = 387) Controls (n = 30) Stage A-B (n = 113) Stage C-HFpEF (n = 101) Stage c-HFrEF (n = 143) p-value Age, years 68.9 ± 11.1 67.1 ± 10.6 67.7 ± 10.4 70.5 ± 10.1 68.5 ± 11 0.1 Male, n (%) 247 (64) 18 (60) 70 (62) 57 (56) 102 (71) 0.1 VO2 @peak, mL/min/kg 15.7 (12.1-19.6) 23 (21.7- 29.7) 18 (15.4- 20.7)* 13.6 (11.8- 16.8)*† 14.2 (10.7- 17.5)*† &amp;lt;0.0001 Workload @peak, W 90 (65-120) 130 (115-195) 110 (84-130)* 70 (55-100)*† 80 (60-110)*† &amp;lt;0.0001 Heart rate @peak, bpm 123 ± 22 142 ± 12 130 ± 20* 115 ± 17*† 119 ± 23*† &amp;lt;0.0001 Stroke volume @peak, mL 83 (71-99) 98 (85-114) 86 (76-107) 83 (74-97)* 75 (63-95)*† &amp;lt;0.0001 Average S" @peak, cm/s 11.2 ± 3.8 17.1 ± 3.9 13.3 ± 2.9* 10.6 ± 2.5*† 8.7 ± 2.7*†‡ &amp;lt;0.0001 TAPSE/PAPs @peak, mm/mmHg 0.75 (0.46-0.97) 1.05 (0.93- 1.16) 0.81 (0.52- 0.91)* 0.52 (0.38- 0.83)*† 0.58 (0.41- 0.89)*† &amp;lt;0.0001 Left atrial reservoir strain/E/e" @low-load, % 2.25 (1.17-5.04) 6.23 (4.45-6.77) 4.34 (3.89- 5.58)* 2.23 (1.31- 2.86)*† 1.91 (1.07-2.44)*†‡ &amp;lt;0.0001 * p &amp;lt; 0.01 vs Controls; † p &amp;lt; 0.01 vs Stage A-B; ‡ p &amp;lt; 0.01 vs Stage C-HFpEF. PAPs systolic pulmonary artery pressure; TAPSE: tricuspid annular plane systolic excursion; VO2: oxygen consumption. Abstract Figure 1

The Physiological Burden of the 6-Minute Walk Test Compared With Cardiopulmonary Exercise Stress Test in Patients With Severe Aortic Stenosis

BackgroundManagement of aortic stenosis (AS) relies on symptoms. Exercise testing is recommended for asymptomatic patients with significant AS but is often experienced as forbidding and/or technically unrealistic for patients who are often frail, deconditioned, and intimidated by the exercise test. We compared the physiological burden assessed with gas exchange assessments to gauge and respiratory exchange ratio (RER) of a 6-minute walk test (6MWT) to a cardiopulmonary exercise stress test (CPET) in patients with severe AS. peak oxygen utilization MethodsAdults with equivocal symptoms and severe AS (1-aortic valve area [AVA] ≤ 1.0 cm2 or AVA index ≤ 0.6 cm2/m2, 2-peak aortic jet velocity ≥ 4.0 m/sec, 3-mean transvalvular pressure gradient ≥ 40 mm Hg by rest or dobutamine stress echocardiography, or 4-aortic valve calcification ≥ 1200 in women or ≥ 2000 AU in men) were studied. All participants completed both a 6MWT and symptom-limited progressive bicycle exercise testing. Breath-by-breath gas analysis and 12-lead electrocardiography were completed during 6MWT and CPET. Results: Eleven patients were studied. Patients walked on average 330 ± 75 m during the 6MWT and achieved a maximal workload of 48 ± 14 watts during the CPET. During the 6MWT, peak maximal oxygen uptake (V˙O2peak) was 12.8 ± 2.5 vs 10.8 ± 4.2 mL/kg/min during the CPET. Respiratory exchange ratio exceeded 1.1 in both the 6MWT and CPET indicating similarly high exertion. Compared with the CPET, a larger proportion of the 6MWT was performed at a high intensity level (78% ± 28% vs 33% ± 24% at > 85% V̇O2peak; P = 0.004). ConclusionsThe 6MWT with breath-by-breath gas analysis was well tolerated and able to achieve a physiological intense RER and V˙O2peak that are similar to symptom-limited CPET in patients with severe AS.

Exercise Ventricular Rates, Cardiopulmonary Exercise Performance, and Mortality in Patients With Heart Failure With Atrial Fibrillation.

In heart failure (HF) with sinus rhythm, resting and exercise heart rates correlate with exercise capacity and mortality. However, in HF with atrial fibrillation (AF), this correlation is unknown. Our aim is to investigate the association of resting and exercise ventricular rates (VRs) with exercise capacity and mortality in HF with AF. We identified 903 patients with HF and AF referred for cardiopulmonary stress testing. AF was defined as history of AF and AF during cardiopulmonary stress testing. We constructed multivariable models to evaluate the association of resting VR, peak exercise VR, VR reserve (peak VR-resting VR), and chronotropic index with (1) peak oxygen consumption (PVO2) ≤18 mL/kg per minute, (2) continuous PVO2, and (3) 10-year all-cause mortality. Median (25th-75th percentile) age was 60 (52-67) years, left ventricular ejection fraction was 25 (15-50)%, and 76.1% were males. Patients with lower (quartile 1) compared with higher (quartile 4) peak VR, VR reserve, and chronotropic index were more likely to have PVO2 ≤18 mL/kg per min (adjusted odds ratio [95% CI]: 14.92 [8.07-27.58], 24.60 [12.36-48.98], and 22.31 [11.24-44.27], respectively), and higher all-cause mortality (adjusted hazard ratio [95% CI]: 2.56 [1.62-4.04], 2.29 [1.47-3.59], and 2.30 [1.51-3.49], respectively). For every 10 beats per minute increase in VR reserve, PVO2 increased by 1.05 mL/kg per minute (B-coefficient [95% CI]: 1.05 [0.94-1.15]) and mortality decreased by 12% (adjusted hazard ratio [95% CI]: 0.88 [0.83-0.94]). Resting VR was associated with PVO2 (B-coefficient [95% CI]: -0.46 [-0.70 to -0.23]) but not mortality (adjusted hazard ratio [95% CI]: 0.97 [0.88-1.06]). In patients with HF and AF, higher resting VR and lower peak exercise VR, VR reserve, and chronotropic index were all associated with worse peak exercise capacity, but only lower exercise VR parameters were associated with higher mortality. Dedicated studies are needed to gauge whether modulating exercise VR enhances exercise performance and outcomes.

Cardiopulmonary Response to Exercise at High Altitude in Adolescents with Congenital Heart Disease

Objective: To extend our knowledge on tolerance of acute high-altitude exposure and hemodynamic response to exercise in adolescents with congenital heart disease (AscCHD) without meaningful clinical or functional restriction. Methods: A symptom limited cardiopulmonary exercise stress test and a non-invasive cardiac output measurement during steady state exercise were performed at 540 m and at 3454 m a.s.l. Symptoms of acute mountain sickness were noted. Results: We recruited 21 healthy controls and 16 AscCHD (59% male, mean age 14.7 ± 1.1 years). Three subjects (2 controls, 1 AscCHD) presented light symptoms of acute mountain sickness (dizziness and headache). During the symptom limited exercise test at lowland, control subjects showed a significantly higher power to weight index (3.5 ± 0.6 W/kg vs. 3.0 ± 0.7 W/kg, p < 0.001), heart rate (188.8 ± 10.4 1/min vs. 179.4 ± 13.1 1/min, p < 0.050) and ventilation (92.8 ± 22.9 l/min vs. 75.4 ± 18.6 l/min,

Predicting the transition to and progression of heart failure with preserved ejection fraction: a weighted risk score using bio-humoural, cardiopulmonary, and echocardiographic stress testing.

Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment. We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B). Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment. We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B). We performed a resting clinical/bio-humoural evaluation and a symptom-limited CPET-ESE in 274 patients (45 Stage A, 68 Stage B, and 161 Stage C-HFpEF) and 30 age- and sex-matched healthy controls. During a median follow-up of 18.5 months, we reported 71 HF hospitalizations and 10 cardiovascular deaths. Cox proportional-hazards regression identified five independent predictors and each was assigned a number of points proportional to its regression coefficient: stress-rest ΔB-lines >10 (3 points), peak oxygen consumption <16 mL/kg/min (2 points), minute ventilation/carbon dioxide production slope ≥36 (2 points), peak systolic pulmonary artery pressure ≥50 mmHg (1 point) and resting N-terminal pro-brain natriuretic peptide (NT-proBNP) >900 pg/mL (1 point). The event-free survival probability for low risk (<3 points), intermediate risk (3-6 points), and high risk (>6 points) were 93%, 52%, and 20%, respectively. The area under the curve (AUC) for the scoring system to predict events was 0.92 (95% CI 0.88-0.96), with an accuracy significantly higher than the individual components of the score (all P < 0.01 vs. individual AUCs). A weighted risk score including NT-proBNP, markers of cardiopulmonary dysfunction and indices of exercise-induced pulmonary congestion identifies HFpEF patients at increased risk for adverse events and Stage A and B subjects more likely to progress towards more advanced HF stages.

Comparative study of cardiorespiratory adaptations in elite basketball players of different age groups.

Systematic training of basketball causes morphological cardiac and cardiorespiratory adaptations. Previous studies have mainly focused either on only cardiac or respiratory changes. However, the extent of these cardiac adaptations and their relationship with aerobic capacity remain unclear in basketball athletes of different ages. Eighty male basketball players participated in the experimental group and 80 healthy and sedentary male individuals served as controls. All participants underwent to athletic history, anthropometric measurements, 12-lead resting electrocardiogram (ECG), echocardiography, resting spirometry and cardiopulmonary exercise stress test. Left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular end-diastolic internal dimension (LVIDd), end-diastolic volume (EDV), stroke volume (SV) and interventricular septal thickness at diastole (IVSd) were significantly higher in all groups of athletes compared to controls (P<0.05). End-diastolic volume index (EDVI) was significantly higher only in adult players compared to controls (P<0.05). Posterior wall thickness at diastole (PWd) was significantly greater in groups of children and adult players compared to controls (P<0.05). Maximal oxygen uptake (V̇O<inf>2max</inf>) in relative values was higher in all groups of athletes compared to controls (P<0.05). The increased LVM is attributed to concentric hypertrophy. This is further supported by the finding that there was no relationship between V̇O<inf>2max</inf> and echo parameters. The results of the present study indicate that the cardiorespiratory adaptations caused by basketball training are mainly formed at the early age stages without further increase throughout the years of action.

Abstract 15381: Subjective and Objective Impact of Angiotensin Receptor-neprilysin Inhibitor on Systemic Right Ventricle Patients

Introduction: Adult Congenital Heart Disease (ACHD) patients have increased mortality and morbidity from heart failure. Angiotensin receptor-Neprilysin Inhibitors (ARNI) have emerged as a standard of therapy for adults with heart failure. These medicines have not been studied in ACHD patients. Hypothesis: ARNIs are associated with subjective and objective improvements in systemic right ventricle (SRV) patients. Methods: Eighteen SRV patients were prescribed ARNI at our institution in the last 3 years. Data including demographics, medical history, New York Heart Association functional class (NYHA FC), labs, 3D imaging, echocardiograms, cardiopulmonary stress test (CPET), and hospitalization were obtained by retrospective electronic chart review. Statistical analysis was performed using paired t and Wilcoxon rank sum tests. Results: Eighteen SRV patients (mean age 40 years, 72% male) were treated with ARNI (median 13 months) and conventional therapy (beta blocker (83%), loop diuretic (89%), antiarrhythmics (33%), and anticoagulation (50%)). Baseline data include: Mean blood pressure 118/75 mmHg, pulse 75 bpm, creatinine 0.86 mg/dL, potassium 4 meq/L, B-type natriuretic peptide (BNP) 322 pg/mL, and NT-Pro BNP 1091 pg/mL. Nine patients were NYHA FC 2, 7 FC 3, and 2 FC 4. High dose was achieved in 3 (17%) patients, and moderate in 3 (17%). CPET and imaging data were: VO2 18 mL/kg/min, VE/VCO2 38, RVEF 32%, FAC 21%, significant TR (12.5% moderate, and 12.5% severe) and TAPSE 9.4. There was no statistically significant difference pre vs post-ARNI in blood pressure, labs (creatinine, potassium, BNP and NT-ProBNP), or testing (VO2 18 vs 17, p=0.432; VEVCO2 38 vs 39, p=0.850; RVEF 32 vs 32%, p=0.648; FAC 18 vs 21%, p=0.489; TR p=0.317; and TAPSE 9.2 vs 9.1, p=0.906). There was a statistically significant improvement in median NYHA FC (2 vs 2.5, p=0.005), especially if baseline NYHA FC&gt;2 (2 vs 3, p=0.011). There was a noted decrease in cardiac hospitalization (4 vs 9) that did not reach statistical significance (p=0.313). Conclusions: ARNIs are associated with noticeable improvement in functional class without impact on objective measures in SRV patients. The study findings are promising and highlight the need for larger, prospective, multicenter studies.

Abstract 15784: Left Ventricular Structural Remodeling and Cardiomyopathy in Duchenne Muscular Dystrophy Carriers

Introduction: Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder. DMD-associated cardiomyopathy is the primary mode of premature death in the majority of male DMD patients, but the prevalence of cardiomyopathy and its clinical significance in female DMD carriers is less well characterized. Hypothesis: We hypothesized that a significant proportion of DMD carriers develop maladaptive left ventricular (LV) structural remodeling and cardiomyopathy over time. Methods: A cross-sectional study was undertaken comparing cardiac magnetic resonance imaging (cMRI) and cardiopulmonary stress test (CPX) parameters between DMD carriers and healthy age- and sex-matched controls from the Dallas Heart Study (DHS). Demographic data, cMRI parameters, and CPX parameters were collected retrospectively on 30 consecutive DMD carriers and 26 control DHS subjects. Results: Overall, DMD carriers had a significantly lower LVEF compared to DHS controls (58+8% vs 70+7%, p&lt; 0.0001). The overall prevalence of reduced LVEF in DMD carriers (defined as LVEF &lt;60%) was 63% compared to 8% in DHS controls. The volumetric variables indexed to body surface area (LVEDVi and LVESVi) were significantly higher in DMD carriers compared to control subjects (72+14 ml/m 2 vs 58+7, p&lt; 0.0001; 31+10 ml/m 2 vs 17+5, p&lt; 0.0001; respectively). LV concentricity was also significantly lower among all DMD carriers compared to DHS controls (3.10+0.65 g/mL 0.67 vs 3.73+0.79, p =0.002). LV concentricity was significantly lower in DMD carriers with reduced EF compared to controls (3.09+0.51 g/mL 0.67 vs 3.73+0.79, p = 0.012), while DMD carriers with preserved EF also had reduced concentricity compared to controls (3.12+0.86 vs 3.73+0.79, p = 0.054). Finally, peak VO 2 was lower in DMD carriers compared to DHS controls (23+6 ml/kg/min vs 25+4, p =0.076), though this difference did not reach statistical significance. Conclusions: Collectively, the data suggest that middle-aged female DMD carriers are at greater risk of developing left ventricular systolic dysfunction and cardiomyopathy associated with decreased exercise capacity. A possible mechanism driving the development of this cardiomyopathy is progressive, maladaptive left ventricular dilatation and cardiac atrophy.

Cardiac Reserve and Exercise Capacity: Insights from Combined Cardiopulmonary and Exercise Echocardiography Stress Testing

Cardiopulmonary exercise testing (CPET) represents the gold standard to estimate peak oxygen consumption (VO2) noninvasively. To improve the analysis of the mechanisms behind effort intolerance, we examined whether exercise stress echocardiography measurements relate to directly measured peak VO2 during exercise in a large cohort of patients within the heart failure (HF) spectrum. We performed a symptom-limited graded ramp bicycle CPET exercise stress echocardiography in 30 healthy controls and 357 patients: 113 at risk of developing HF (American College of Cardiology/American Heart Association stage A-B) and 244 in HF stage C with preserved (HFpEF, n=101) or reduced ejection fraction (HFrEF, n=143). Peak VO2 significantly decreased from controls (23, 21.7-29.7mL/kg/minute; median, interquartile range) to stage A-B (18, 15.4-20.7mL/kg/minute) and stage C (HFpEF: 13.6, 11.8-16.8mL/kg/minute; HFrEF: 14.2, 10.7-17.5mL/kg/minute). A regression model to predict peak VO2 revealed that peak left ventricular (LV) systolic annulus tissue velocity (S'), peak tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (right ventricle-pulmonary artery coupling), and low-load left atrial (LA) reservoir strain/E/e' (LA compliance) were independent predictors, in addition to peak heart rate, stroke volume, and workload (adjusted R2=0.76, P<.0001). The model was successfully tested in subjects with atrial fibrillation (n=49) and with (n=224) and without (n=163) beta-blockers (all P<.01). Peak S' showed the highest accuracy in predicting peak VO2<10mL/kg/minute (cut point≤7.5cm/sec, area under the curve=0.92, P<.0001) and peak VO2>20mL/kg/minute (cut point>12.5cm/sec, area under the curve=0.84, P<.0001) in comparison with the other cardiac variables of the model (P<.05). Peak VO2 is directly related to measures of LV systolic function, LA compliance, and right ventricle-pulmonary artery coupling, in addition to heart rate and stroke volume and independently of workload, age, and sex. The evaluation of cardiac mechanics may provide more insights into the causes of effort intolerance in subjects from HF stages A-C.

TOO MUCH TESTOSTERONE CAN MAKE IT HARD TO BREATHE

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Testosterone replacement therapy for hypogonadism can be prescribed through topical/transdermal and intramuscular injections. Recognized treatment risks include prostate cancer, benign prostatic hypertrophy, erythrocytosis, and venous thromboembolism. There have been concerns for possible cardiovascular side effects from testosterone supplementation as well. Here we discuss a patient with worsening shortness of breath and subthreshold erythrocytosis in the setting of intramuscular (IM) testosterone supplementation. CASE PRESENTATION: A 43 year old man with a history of hypertension, CPAP-treated obstructive sleep apnea, and hypogonadism presented with 2 months of slowly progressive dyspnea on exertion and flushing occurring with activity or after a shower. He reported no chest pain, wheezing, cough, headache or dizziness. His physical exam was normal. Extensive evaluation included a resting echocardiogram showing preserved ejection fraction, no valvular dysfunction, and no signs of pulmonary hypertension. Cardiopulmonary exercise stress test was normal. PFTs excluded obstructive or restrictive ventilatory defects; lung volumes were normal and DLCO was 101% predicted. CT chest showed a 1 cm RML endobronchial nodule; subsequent PET scan showed no FDG uptake in the nodule or elsewhere. A hemoglobin of 17.7 g/dl, elevated compared with prior values, decreased to 14.3 g/dl over three months following cessation of IM testosterone therapy and his dyspnea improved without other changes in therapy or management. He was switched to a topical testosterone supplement with no rise in hemoglobin nor return of dyspnea. DISCUSSION: Polycythemia is a well-known side effect from testosterone injections and monitoring is advised with guidelines suggesting holding testosterone for a hemoglobin of 18 g/dl or a hematocrit of 54%. Erythrocytosis is of concern due to the increased risk of hyperviscosity syndrome whose symptoms including blurred vision, headaches, chest pain, weakness, and paresthesia. Case reports have associated IM testosterone with lower extremity edema too. This patient’s successful transition to transdermal testosterone is concordant with prior reports of a reduced risk of elevated hemoglobin with transdermal therapy. CONCLUSIONS: Testosterone supplementation requires routine monitoring due to risk of erythrocytosis and associated hyperviscosity syndrome, prostate cancer, and thromboembolism. In this patient, a new manifestation of dyspnea and subthreshold polycythemia co-occurred with IM testosterone and abated with discontinuation and transition to transdermal forms. A thorough review of other medical history and medications continues to be needed in patient on testosterone when present with cardiorespiratory symptoms to ensure accurate identification of the underlying cause. Reference #1: Keohane, C., et al. “The Diagnosis and Management of Erythrocytosis.” Bmj, vol. 347, no. nov18 1, 2013, doi:10.1136/bmj.f6667 Reference #2: Basaria, Shehzad, et al. “Adverse Events Associated with Testosterone Administration.” New England Journal of Medicine, vol. 363, no. 2, 2010, pp. 109–122., doi:10.1056/nejmoa1000485 Reference #3: Surampudi, Prasanth N., et al. “Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy.” International Journal of Endocrinology, vol. 2012, 2012, pp. 1–20., doi:10.1155/2012/625434 DISCLOSURES: Site PI for pharmaceutical trials relationship with Boehringer-Ingelheim Please note: $1001 - $5000 Added 06/01/2020 by Rebecca Bascom, source=Web Response, value=Travel Site PI for pharmaceutical study relationship with Nitto Denko Please note: $1001 - $5000 Added 06/01/2020 by Rebecca Bascom, source=Web Response, value=Travel Site PI for pharmaceutical study relationship with Galapagos Please note: $1001 - $5000 Added 06/01/2020 by Rebecca Bascom, source=Web Response, value=Travel Other relationship with Nitto Denko Please note: $1001 - $5000 by Rebecca Bascom, source=Web Response, value=Travel Other relationship with Galapagos Please note: $1001 - $5000 by Rebecca Bascom, source=Web Response, value=Travel attended investigator meeting relationship with Nitto Denko Please note: $1001 - $5000 by Rebecca Bascom, source=Web Response, value=Travel attended investigator meeting relationship with Galapagos Please note: $1001 - $5000 by Rebecca Bascom, source=Web Response, value=Travel No relevant relationships by Ibrahim Ismail-Sayed, source=Web Response No relevant relationships by Kathleen Twomey, source=Web Response

Myocardial Recovery in Dilated Cardiomyopathy with Goal Directed Medical Therapy

Background Dilated cardiomyopathy (DCM) is a common cause of heart failure (HF). Goal Directed Medical Therapy (GDMT) for HF has been shown to improve mortality and morbidity but rate of myocardial recovery is not well known. Methods In this retrospective study, 325 patients with newly diagnosed systolic heart failure (LVEF 10% and maintained >6 months. At baseline, all patients underwent echocardiogram; additionally, 22% underwent cardiac MRI, 7% cardiopulmonary stress test and 14% right heart catherization. GDMT was initiated inpatient and titrated weekly the first month, biweekly for the second month and monthly thereafter in our HF clinic. At discharge, 25% of the patients were sent home with wearable cardioverter-defibrillator (WCD). Results Of the 325 patients, 148 patients (45.5%) had myocardial recovery. In the recovery group, average age was 55.0 years, 58.8% were males, 64.9% Caucasians and 30.0% African Americans. At baseline, average LVEF was 27.3% and NYHA class 2.3. Average time for myocardial recovery was four months post initiation of GDMT. At one-year follow-up, average LVEF was 48.6% and NYHA class 1.7. In the recovery group, 84.0% were on ACEI/ARB/ARNI, 95.3% BB, 59.5% MRA, 4.7% Hydralazine, 2.7% Nitrates and 13.4% on Digoxin. No malignant arrhythmias were noted in patients discharged with WCD. The 30-day HF readmission rate in the myocardial recovery group was Conclusion GDMT for HF is well established and with aggressive medication titration in newly diagnosed systolic HF due to DCM and NICM, myocardial recovery is possible with rates as high as 45.5% at one-year.

Tolerability and Effect of Angiotensin Receptor Neprilysin Inhibitors in Adult Congenital Patients with Systemic Right Ventricle

Introduction Adult Congenital Heart Disease (ACHD) patients have an increased mortality and morbidity from heart failure. Angiotensin Receptor-Neprilysin Inhibitors (ARNI) have emerged as a standard of therapy for adults with heart failure. However, the effects of these medicines have not been studied in ACHD patients. Hypothesis ARNI's are well tolerated and have beneficial cardiovascular effects in ACHD patients. Method Twenty-one ACHD patients with systemic right ventricle were prescribed ARNI at our institution. Demographics, vital signs, laboratory results, functional status, imaging data, and outcomes were collected by retrospective electronic review. Statistical analysis was performed using paired t test. Results Twenty-one patients with systemic right ventricle were treated with ARNI: 16 D-Transposition of great arteries (TGA) with atrial switch, 1 congenitally corrected TGA, and 1 Taussig Bing transposition type and atrial switch. Fifteen (71.4%) were male, mean age 39.8±6.5 years. Baseline RVEF was 33.4+/-8.6%. Baseline peak VO2 was 18.1+/-4.3 mL/min/kg. By functional status, 10 were in NYHA class II (50%), 7 in class III (35%), and 2 in class IV (one unknown). Median follow-up was 14.1 (9.4-27.8) months. All patients tolerated Entresto for at least six months. High dose Entresto was achieved in 4 (19%) patients, 3 (14.3%) were on moderate dose, and 14 (66.7%) were on low dose. Only 2 (9.5%) patients discontinued Entresto after 9 and 11 months due to hypotension. There was no significant change in creatinine (0.8±0.4 mg/dL versus 1.0±0.3 mg/dL, p=NS), no incidence of hyperkalemia, angioedema, or major side effect including death. Systolic blood pressure was 118.2+/-14.2 mmHg at baseline and decreased with ARNI use (112.4+/-16.4 mmHg at 0-3 months, 112.4+/-12.8mmHg at 3-6 months and 108.5+/-10.3mmHg at 6-12 months, p values by paired t test 0.02, NS, and NS respectively). Corresponding values for diastolic blood pressure were 74.5+/-9.6mmHg (baseline), 72.4+/-14.3mmHg, 62.8+/-10.1 and 70.45+/-10.9mmHg (p values by paired t test NS, 0.009, and NS respectively). Mean NYHA class improved from 2.65+/-0.74 to 2.21+/-0.71 (p=0.008 by paired t-test). 5/12 (42%) of patients had an improvement in peak oxygen consumption on cardiopulmonary stress test, though this was not statistically significant. (16.8+/-4.8 mL/kg/min versus baseline 18.1+/-4.3 mL/min/kg, p=NS). Conclusion ARNI's are safe and well tolerated in ACHD patients. It is associated with mild decrease in blood pressure and improvement in functional class. The study findings are promising and highlight the need for larger, prospective, multicenter studies.

Hypotensive Response on Cardiopulmonary Stress Test Predicts Elevated Pulmonary Capillary Wedge Pressure and Reduced Cardiac Output in Patients Undergoing Evaluation for Left Ventricular Assist Device

Purpose Cardiopulmonary stress test (CPX) and right heart catheterization (RHC) are integral part of the routine evaluation for ventricular assist device (LVAD) therapy. A hypotensive response, or failure to augment systolic blood pressure at peak stress above resting values might be a marker of high-risk physiology. We sought to evaluate the association between hypotensive response on CPX and invasive hemodynamics in patients undergoing LVAD evaluation. Methods This was a retrospective single center study of consecutive adult patients who underwent LVAD surgery at our center between 1/2011 and 1/2019. Only patients with both CPX and RHC performed within 12 months of implantation were included. Hypotensive response was defined as a peak exercise systolic blood pressure lower than the resting systolic blood pressure. Central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP) and cardiac index determined using the thermodilution method (CI) were collected from RHC data. Multivariable Cox regression analysis was performed to evaluate the association between CPX data and hemodynamics. Results A total of 313 patients were included in the study and 115 met inclusion criteria. The mean age was 60.1 years, 66% were designated bridge to transplant (BTT) and the majority (85%) were classified as INTERMACS 3-5. Forty seven percent (54/115) developed a hypotensive response during testing. The group had a mean PCWP of 23.7 mmHg and a mean CI of 1.7 L/min/m2. In contrast, patients with normal blood pressure response had a significantly lower PCWP (19.8 mmHg; P=0.011) and significantly higher CI (2.0 L/min/m2; p=0.030). There was no difference in CVP values between the groups. Mean exercise duration was 6 minutes and 1 seconds in the hypotensive group, and 7 minutes 8 seconds in the group with normal blood pressure response. Conclusion A hypotensive response on CPX performed prior to LVAD implantation is associated with more severely abnormal hemodynamics. Identification of this high risk feature earlier has the potential to improve outcomes by preventing late LVAD implantation.

Hypotensive Response on Cardiopulmonary Stress Test is Associated with Increased One Year Mortality After Continuous Flow Left Ventricular Assist Device Implantation

Purpose Cardiopulmonary stress testing (CPX) is widely used to evaluate patients with end stage heart failure who may benefit from advanced therapies, such as durable left ventricular assist devices (LVAD). A hypotensive systolic blood pressure response on CPX may identify a subpopulation with the highest risk physiology. We sought to evaluate long term outcomes among LVAD recipients with a pre-implantation hypotensive response. Methods This was a retrospective single center study using consecutive patients implanted with a continuous flow LVAD between 1/2011 and 1/2019 at our Institution. Patients with CPX performed within 12 months before implantation were included. Hypotensive response was defined as a peak exercise systolic blood pressure lower than the resting systolic blood pressure. The primary outcome was 1-year mortality. Multivariable cox regression analysis was performed to evaluate the relationship between hypotensive exercise blood pressure response and mortality. Multivariate linear regression analysis was used to determine pre-implant variables and mortality. Results 313 patients were enrolled in the study and 123 were identified to meet our inclusion criteria. The mean age was 60.1 years, 58% had ischemic cardiomyopathy and 85% were classified as INTERMACS 3-5. 54 patients had a hypotensive response on CPX (44%). A total of 14 patients died at 1 year, 10 from the hypotensive cohort (p=0.043), hazard ratio 3.54 with 95% CI (1.1, 11.3, p=0.033). Post-implantation ICU and overall hospital length of stay were similar to the group with normal blood pressure response. There was also no significant difference in post-operative complications and the risk of re-hospitalization at 1 month, 6 months and 1 year. Conclusion Hypotensive blood pressure response on the CPX performed pre-LVAD implantation is independently associated with increased 1-year mortality. Additional studies are needed to further characterize this high-risk patient population and to identify strategies to improve survival rates.

Exercise Oscillatory Ventilation is Independently Associated with Right Ventricular Systolic Dysfunction in Patients with Chronic Heart Failure

Background Exercise Oscillatory Ventilation (EOV) is a crucial marker for disease severity and prognosis in chronic heart failure (HF) patients. Although the presence of EOV in chronic HF patients has been demonstrated the association with worse left ventricular (LV) function, the evidence regarding with right ventricular (RV) function is still lacking. This study aim was to determine the association of EOV and RV systolic function in chronic heart failure patients. Method We retrospectively analyzed a cardiopulmonary exercise stress testing (CPET) database in 709 chronic HF patients at Cleveland Clinic, between April 2018 and June 2019. RV systolic dysfunction was determined by tricuspid annular plane systolic excursion (TAPSE) Results The prevalence of EOV in chronic HF patients with RV systolic dysfunction was significantly higher than those without RV systolic dysfunction (75.7% vs. 24.3%, p Conclusion In the large contemporary cohort, exercise oscillatory ventilation was independently associated with RV systolic dysfunction in chronic heart failure patients.

Normative Values for Cardiopulmonary Exercise Stress Testing Using Ramp Cycle Ergometry in Children and Adolescents

To provide sex, age, and race specific reference values for ramp cycle ergometer cardiopulmonary exercise test (CPET) in children in the US. Retrospective review was conducted of all cardiopulmonary CPET data from our Exercise Physiology Laboratory on healthy children and adolescents (6-18years) with body mass index between the 5th and 95th percentiles and structurally normal hearts who performed a ramp cycle ergometry stress test between 1999 and 2015. Twenty-eight exercise variables were included: peak oxygen consumption, oxygen consumption at ventilatory anaerobic threshold, peak work rate, resting and peak heart rate and blood pressure, resting pulmonary function testing, and ventilatory responses to progressive exercise using breath-by-breath gas exchange. Owing to the nonlinear association between CPET results and age, fractional polynomials were used in the mixed-effects regression models to describe the sex- and age-specific normative values with 95% CIs, after adjusting for race and body mass index. We analyzed data on 1829 children (average age, 13.6±2.6years; 52% male). After 12years of age, males generally had higher peak values for aerobic capacity and work rate. There were progressive increases with age for both sexes in resting pulmonary function and ventilatory response to exercise, peak aerobic and work rate, and oxygen pulse. Notably, there was an age-related decrease in ventilatory equivalents of oxygen and carbon dioxide at the ventilatory anaerobic threshold. Future research using prospective, inclusive, and statistically planned cohorts with standardized laboratory approaches and confirmed interoperability should be considered as a focus for validating normative pediatric CPET values in the future.

Do Cheyne and Stokes have an important message for modern‐day patients with heart failure? Yes, they do

Do <scp>C</scp>heyne and <scp>S</scp>tokes have an important message for modern‐day patients with heart failure? <scp>Y</scp>es, they do

Sacubitril/Valsartan Improves Autonomic Function and Cardiopulmonary Parameters in Patients with Heart Failure with Reduced Ejection Fraction

Background: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. Methods: Patients with HFrEF admitted to outpatients’ services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. Results: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO2slope (r = −0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO2slope (Beta (B) = −0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = −0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = −2.065, SE = 0.354, p < 0.001). Conclusions: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.