Author Archives: Paul Older

Determinants of Cardiorespiratory Fitness in Patients with Heart Failure Across a Wide Range of Ejection Fractions.

The American Journal Of Cardiology [Am J Cardiol] 2019 Oct 10. Date of Electronic Publication: 2019 Oct 10.

van Wezenbeek J; Canada JM; Ravindra K; Carbone S; Kadariya D; Trankle CR; Wohlford G; Buckley L; Del Buono MG; Viscusi M; Tchoukina I; Shah KB; VCU Arena R; Van Tassell B; Abbate A;

The American Journal Of Cardiology [Am J Cardiol] 2019 Oct 10. Date of Electronic Publication: 2019 Oct 10.

Impaired cardiorespiratory fitness (CRF) in heart failure (HF) is influenced by a complex array of cardiac and extracardiac factors. The study aimed to identify clinical determinants of CRF measured as peak oxygen consumption (peak VO2) in HF patients, and to determine a peak VO2 prediction model using regression equations. Retrospective analysis of 200 HF patients who completed treadmill cardiopulmonary exercise testing and underwent Doppler echocardiography and/or biomarker analysis on the same day was performed. After univariate linear regression analysis, a multivariate peak VO2 prediction model was developed using significant variables in a stepwise linear regression analysis. In subjects with repeated testing, Pearson’s correlation was used to assess correlations between measured and predicted change in peak VO2 (Δpeak VO2) over time. Mean age was 57 years, with 55% being male. Stepwise linear regression was used to generate a weighted model for peak VO2: 30.895 + (-0.112•age[years]) + (0.296•hemoglobin [g/dl]) + (-0.101•E/e'[unit change]) + (-0.202• body mass index [kg/m2]) + (-0.593• N-terminal pro-brain natriuretic peptide [logN pg/ml])) + (-1.349•CRP [log mg/L]). Predicted peak VO2 correlated strongly with measured peak VO2 in HF with reduced ejection fraction and HF with preserved ejection fraction patients (r = +0.63, p <0.001; r = +0.64, p <0.001, respectively). Predicted Δpeak VO2 correlated with measured Δpeak VO2 (r = +0.23, p <0.001).
In conclusion, in patients with HF across a wide range of left ventricular ejection fraction, age, systemic inflammation, oxygen carrying capacity, obesity, and elevated filling pressures are the strongest predictors of impaired CRF. The proposed CRF model allows prediction of peak VO2 in HF patients and may be used to estimate peak VO2 changes over time.

Cardiorespiratory fitness and right ventricular mechanics in uncomplicated diabetic patients: Is there any relationship?

Vukomanovic V; Suzic-Lazic J; Celic V; Cuspidi C; Skokic D; Esposito A; Grassi G; Tadic M;

Acta Diabetologica [Acta Diabetol] 2019 Nov 08. Date of Electronic Publication: 2019 Nov 08.

Aims: This study investigated the association between cardiorespiratory fitness and right ventricular (RV) strain in uncomplicated diabetic patients.
Methods: This cross-sectional study involved 70 controls and 61 uncomplicated patients with type 2 diabetes, who underwent laboratory analysis, comprehensive echocardiographic study and cardiopulmonary exercise testing.
Results: RV endocardial and mid-myocardial longitudinal strains were significantly reduced in diabetic subjects (- 27.5 ± 4.2% vs. - 25.3 ± 4.3%, p = 0.004 for endocardial strain; - 25.6 ± 3.5% vs. - 24.1 ± 3.2%, p = 0.012 for mid-myocardial strain). The same was revealed for endocardial and mid-myocardial of RV free wall. There was no difference in RV epicardial strain. VO2 was significantly lower in the diabetic group (27.8 ± 4.5 ml/kg/min vs. 21.5 ± 4.2 ml/kg/min, p < 0.001), whereas ventilation/carbon dioxide slope was significantly higher in diabetic subjects (25.4 ± 2.9 vs. 28.6 ± 3.3). Heart rate recovery was significantly lower in diabetic patients. HbA1c and global RV endocardial longitudinal strain were independently associated with peak VO2 and oxygen pulse in the whole study population.
Conclusion: Diabetes impacts RV mechanics, but endocardial and mid-myocardial layers are more affected than epicardial layer. RV endocardial strain and HbA1c were independently associated with cardiorespiratory fitness in the whole study population. Our findings show that impairment in RV strain and cardiorespiratory fitness may be useful indicators in early type 2 diabetes, prior to the development of further complications.

Incidence and Predictors of Clinically Important and Dangerous Arrhythmias During Exercise Tests in Pediatric and Congenital Heart Disease Patients.

Barry OM; Gauvreau K; Reichman JR; Bourette L; Curran T; O’Neill J; Pymm JL; Alexander ME;

JACC. Clinical Electrophysiology [JACC Clin Electrophysiol] 2018 Oct; Vol. 4 (10), pp. 1319-1327. Date of Electronic Publication: 2018 Jul 25.

Objectives: This study quantified the incidence of arrhythmias during pediatric exercise stress tests (ESTs) and evaluated criteria to identify patients at risk of clinically important arrhythmias.
Background: The incidence of clinically important arrhythmias during pediatric ESTs and criteria for identifying high-risk patients are poorly characterized.
Methods: A retrospective review of ESTs performed from 2013 to 2015 was studied. Arrhythmias were categorized into 4 classes based on need for test termination and intervention. Risk factors evaluated included having an implantable cardioverter-defibrillator (ICD), cardiomyopathy, severe ventricular dysfunction, complex arrhythmia history, coronary disease with concern for ischemia, pulmonary hypertension, select poorly palliated congenital heart disease (CHD), and concerning symptoms. Negative predictive values (NPVs) were calculated.
Results: During the study period, 5307 ESTs were performed. Median age of the subjects was 16 years (interquartile range: 13 to 24 years); 20% had complex CHD. At least 1 high-risk criterion was present in 507 tests (10%); having an ICD (37%) and cardiomyopathy (36%) were the most common criteria. Some arrhythmias were seen in 46% of tests, but only 33 events (0.6%) required test termination. Three events (0.06%) required cardiopulmonary resuscitation, all with high-risk criteria. Absence of a high-risk criterion had a 99.7% (95% confidence interval [CI]: 99.5% to 99.8%) NPV for an arrhythmia that required test termination and a 99.96% (95% CI: 99.85% to 99.99%) NPV for an arrhythmia that required intervention beyond test termination.
Conclusions: Although self-terminating arrhythmias are common, dangerous arrhythmias are rare during ESTs in a high-volume pediatric cardiology program. Pre-defined high-risk criteria identified all patients with the most serious events. The absence of any criteria predicted a low risk for arrhythmias that required test termination. These data permitted informed choices regarding supervision of ESTs.

Peak Work Rate during Exercise Could Detect Frailty Status in Elderly Patients with Stable Heart Failure.

Kawashima K; Hirashiki A; Nomoto K; Kokubo M; Shimizu A; Sakurai T; Kondo I; Arai H; Toba K; Murohara T;

International Heart Journal [Int Heart J] 2019 Nov 15. Date of Electronic Publication: 2019 Nov 15.

The Kihon Checklist (KCL) is a reliable tool for determining frailty status in the elderly. However, there is no information in the literature about the relationship between frailty status and exercise capacity. Here, we examined the associations between cardiopulmonary exercise testing parameters and frailty status in elderly patients with stable heart failure (HF).Ninety-two elderly patients with stable HF were evaluated using cardiopulmonary exercise testing and the KCL. A KCL score of 0-3 was classified as robust, 4-7 as pre-frail, and ≥ 8 as frail. Mean age, peak VO2, and KCL score were 81.7 years, 13.2 mL/kg/minute, and 10.7, respectively. KCL score was significantly correlated with peak VO2 (r = -0.527, P < 0.001) and peak work rate (r = -0.632, P < 0.001). In patients with frailty (n = 63), the peak work rate (WR) was significantly lower than it was in patients without frailty (n = 29; 39.9 versus 69.5 W, respectively; P < 0.001). Multivariate analysis revealed that peak WR and peak systolic blood pressure were significant, independent predictors of frailty (β = -0.108 and -0.045, respectively). In a diagnostic performance plot analysis, a cutoff value for peak WR of 51.9 W was the best predictor of frailty.Frailty status was significantly associated with peak WR and peak systolic blood pressure in elderly patients with stable HF. Therefore, cardiopulmonary exercise testing may be useful for assessing frailty status in this patient population.

Type 2 Diabetes Mellitus, Glycated Hemoglobin Levels, and Cardiopulmonary Exercise Capacity in Patients With Ischemic Heart Disease.

Uribe-Heredia G; Arroyo-Espliguero R; Viana-Llamas MC; Piccone-Saponara LG; Álvaro-Fernández H;
García-Magallón B; Torán-Martínez C; Silva-Obregón A; Izquierdo-Alonso JL

Journal Of Cardiopulmonary Rehabilitation And Prevention [J Cardiopulm Rehabil Prev] 2019 Nov 08. Date of Electronic Publication: 2019 Nov 08.

Purpose: Diabetes mellitus (DM) is associated with long-term cardiovascular complications, including ischemic heart disease (IHD). Nonetheless, DM may directly impair myocardial and lung structure and function. The aim of this study was to assess the impact of type 2 DM (T2DM) and glycemic control on cardiopulmonary exercise capacity in patients with IHD.
Methods: The study involved a cross-sectional analysis of 91 consecutive patients (57 ± 10 yr, 90% men) who underwent a cardiopulmonary exercise test at the beginning of an exercise-based standard phase-II cardiac rehabilitation program, 2 to 3 mo after an acute coronary syndrome. Association of T2DM with cardiopulmonary exercise test parameters was assessed using multiple linear regression analysis controlling for prespecified potential confounders.
Results: There were 26 (29%) diabetic subjects among IHD patients included in the study. After adjustment, T2DM was an independent predictor of a reduced peak oxygen uptake (VO2peak) (P = .005), a reduced pulse O2 trajectory (P = .001), a steeper minute ventilation to carbon dioxide output (VE/VCO2) slope (P = .046), and an increased dead space-to-tidal volume ratio (VD/VT) at peak exercise (P = .049). Glycated hemoglobin (HbA1c) levels were significantly associated with a reduced forced expiratory volume in the first second of expiration (FEV1) (P = .013), VE (P = .001), and VT (P = .007). VO2peak (P trend < .001), VO2 at anaerobic threshold (P trend < .001), and pulse O2 trajectory (P trend < .001) decreased among HbA1c tertiles.
Conclusions: Patients with IHD and a previous diagnosis of T2DM had a reduced aerobic capacity and a ventilation-perfusion mismatch compared with nondiabetic patients. Poor glycemic control in men further deteriorates aerobic capacity probably due to ventilatory inefficiency

Veterans with Gulf War Illness exhibit distinct respiratory patterns during maximal cardiopulmonary exercise.

Lindheimer JB; Cook DB; Klein-Adams JC; Qian W; Hill HZ; Lange G; Ndirangu DS; Wylie GR; Falvo MJ;

Plos One [PLoS One] 2019 Nov 12; Vol. 14 (11), pp. e0224833. Date of Electronic Publication: 20191112 (Print Publication: 2019).

Introduction: The components of minute ventilation, respiratory frequency and tidal volume, appear differentially regulated and thereby afford unique insight into the ventilatory response to exercise. However, respiratory frequency and tidal volume are infrequently reported, and have not previously been considered among military veterans with Gulf War Illness. Our purpose was to evaluate respiratory frequency and tidal volume in response to a maximal cardiopulmonary exercise test in individuals with and without Gulf War Illness.
Materials and Methods: 20 cases with Gulf War Illness and 14 controls participated in this study and performed maximal cardiopulmonary exercise test on a cycle ergometer. Ventilatory variables (minute ventilation, respiratory frequency and tidal volume) were obtained and normalized to peak exercise capacity. Using mixed-design analysis of variance models, with group and time as factors, we analyzed exercise ventilatory patterns for the entire sample and for 11 subjects from each group matched for race, age, sex, and height.
Results: Despite similar minute ventilation (p = 0.57, η2p = 0.01), tidal volume was greater (p = 0.02, η2p = 0.16) and respiratory frequency was lower (p = 0.004, η2p = 0.24) in Veterans with Gulf War Illness than controls. The findings for respiratory frequency remained significant in the matched subgroup (p = 0.004, η2p = 0.35).
Conclusion: In our sample, veterans with Gulf War Illness adopt a unique exercise ventilatory pattern characterized by reduced respiratory frequency, despite similar ventilation relative to controls. Although the mechanism(s) by which this pattern is achieved remains unresolved, our findings suggest that the components of ventilation should be considered when evaluating clinical conditions with unexplained exertional symptoms.

Limited Exercise Capacity in Patients with Systemic Sclerosis: Identifying Contributing Factors with Cardiopulmonary Exercise Testing.

Martis N, Queyrel-Moranne V, Launay D, Neviere R, Fuzibet JG, Marquette CH, Leroy S

J Rheumatol. 2018 Jan;45(1):95-102. doi: 10.3899/jrheum.161349. Epub 2017 Nov 1.

OBJECTIVE: Exercise limitation in patients with systemic sclerosis (SSc) is often
multifactorial and related to complications such as interstitial lung disease
(ILD), pulmonary vasculopathy (PV), left ventricular dysfunction (LVD), and/or
peripheral/muscular limitation (PML). We hypothesized that cardiopulmonary
exercise testing (CPET) could not only suggest and rank competing etiologies, but
also highlight peripheral impairment.
METHODS: Clinical, resting pulmonary function testing, and CPET data from
patients with SSc referred for exercise limitation between October 2009 and
November 2015 were retrospectively analyzed in this bi-center study. Patients
were categorized as having ILD, PV, LVD, and/or PML based on CPET response
patterns and the diagnoses were matched with results from the reference
investigations. The latter consisted of transthoracic echocardiography, chest
computed tomography scan, and right heart catheterization (RHC).
RESULTS: Twenty-seven patients presented with CPET profiles consistent with ILD
(n = 16), PV (n = 15), LVD (n = 5), and PML (n = 19). None of the subjects had a
normal CPET profile. There was a statistically significant negative correlation
between resting DLCO, on the one hand, and dead space to tidal volume ratio and
alveolar-arterial gradient [P(Ai-a)O2] on the other (p < 0.005). CPET identified
90% of patients with a mean pulmonary arterial pressure at rest ≥ 21 mmHg
measured by RHC (n = 10). Peak P(Ai-a)O2, taken independently from other
variables, was crucial in distinguishing subjects with ILD from those without ILD
(p < 0.05).
CONCLUSION: CPET is useful for the characterization of multifactorial exercise
limitation in patients with SSc and in identifying SSc-related complications such
as ILD and PV. This study also identifies PML as an underestimated cause of
exercise limitation.

Exercise testing for assessment of heart failure in adults with congenital heart disease.

Burstein DS; Menachem JN; Opotowsky AR;

Heart Failure Reviews [Heart Fail Rev] 2019 Nov 04. Date of Electronic Publication: 2019 Nov 04.

Congenital heart disease (CHD)-related heart failure is common and associated with significant morbidity, mortality, and resource utilization. In adults with CHD (ACHD), exercise limitation is often underestimated. Quantitative assessment with cardiopulmonary exercise testing (CPET) provides a comprehensive evaluation of exercise capacity and can help risk stratify patients, particularly across serial testing. CPET parameters must be interpreted within the context of the underlying anatomy, specifically for patients with either single ventricle physiology and/or cyanosis. Acknowledging differences in CPET parameters between ACHD and non-ACHD patients with heart failure are also important considerations when evaluating the overall benefit of advanced heart failure therapies. CPET testing can also guide safe exercise recommendation, including those with ACHD-related heart failure.

Post-discharge impact and cost-consequence analysis of prehabilitation in high-risk patients undergoing major abdominal surgery: secondary results from a randomised controlled trial

Barberan-Garcia, A.Ubre, M.Pascual-Argente, N.Risco, R.Faner, J.Balust, J.Lacy, A. M.Puig-Junoy, J.Roca,
Martinez-Palli, G.

Br J Anaesth. 2019;123(4):450-456.

BACKGROUND: Prehabilitation may reduce postoperative complications, but sustainability of its health benefits and impact on costs needs further evaluation. Our aim was to assess the midterm clinical impact and costs from a hospital perspective of an endurance-exercise-training-based prehabilitation programme in high-risk patients undergoing major digestive surgery.
METHODS: A cost-consequence analysis was performed using secondary data from a randomised, blinded clinical trial. The main outcomes assessed were (i) 30-day hospital readmissions, (ii) endurance time (ET) during an exercise testing, and (iii) physical activity by the Yale Physical Activity Survey (YPAS). Healthcare use for the cost analysis included costs of the prehabilitation programme, hospitalisation, and 30-day emergency room visits and hospital readmissions.
RESULTS: We included 125 patients in an intention-to-treat analysis. Prehabilitation showed a protective effect for 30-day hospital readmissions (relative risk: 6.4; 95% confidence interval [CI]: 1.4-30.0). Prehabilitation-induced enhancement of ET and YPAS remained statistically significant between groups at the end of the 3 and 6 month follow-up periods, respectively (DeltaET 205 [151] s; P=0.048) (DeltaYPAS 7 [2]; P=0.016). The mean cost of the programme was euro389 per patient and did not increment the total costs of the surgical process (euro812; CI: 95% -878 – 2642; P=0.365).
CONCLUSIONS: Prehabilitation may result in health value generation. Moreover, it appears to be a protective intervention for 30-day hospital readmissions, and its effects on aerobic capacity and physical activity may show sustainability at midterm.

Sex Differences in Cardiometabolic Traits and Determinants of Exercise Capacity in Heart Failure With Preserved Ejection Fraction.

Lau ES, Cunningham T, Hardin KM, Liu E, Malhotra R, Nayor M, Lewis GD, Ho JE

JAMA Cardiol. 2019 Oct 30. doi: 10.1001/jamacardio.2019.4150. [Epub ahead of

Importance: Sex differences in heart failure with preserved ejection fraction
(HFpEF) have been established, but insights into the mechanistic drivers of these
differences are limited.
Objective: To examine sex differences in cardiometabolic profiles and exercise
hemodynamic profiles among individuals with HFpEF.
Design, Setting, and Participants: This cross-sectional study was conducted at a
single-center tertiary care referral hospital from December 2006 to June 2017 and
included 295 participants who met hemodynamic criteria for HFpEF based on
invasive cardiopulmonary exercise testing results. We examined sex differences in
distinct components of oxygen transport and utilization during exercise using
linear and logistic regression models. The data were analyzed from June 2018 to
May 2019.
Main Outcomes and Measures: Resting and exercise gas exchange and hemodynamic
parameters obtained during cardiopulmonary exercise testing.
Results: Of 295 participants, 121 (41.0%) were men (mean [SD] age, 64 [12] years)
and 174 (59.0%) were women (mean [SD] age, 61 [13] years). Compared with men,
women with HFpEF in this tertiary referral cohort had fewer comorbidities,
including diabetes, insulin resistance, and hypertension, and a more favorable
adipokine profile. Exercise capacity was similar in men and women (percent
predicted peak oxygen [O2] consumption: 66% in women vs 68% in men; P = .38), but
women had distinct deficits in components of the O2 pathway, including worse
biventricular systolic reserve (multivariable-adjusted analyses: ΔLVEF β = -1.70;
SE, 0.86; P < .05; ΔRVEF β = -2.39, SE=0.80; P = .003), diastolic reserve
(PCWP/CO: β = 0.63; SE, 0.31; P = .04), and peripheral O2 extraction (C(a-v)O2
β=-0.90, SE=0.22; P < .001)).
Conclusions and Relevance: Despite a lower burden of cardiometabolic disease and
a similar percent predicted exercise capacity, women with HFpEF demonstrated
greater cardiac and extracardiac deficits, including systolic reserve, diastolic
reserve, and peripheral O2 extraction. These sex differences in cardiac and
skeletal muscle responses to exercise may illuminate the pathophysiology
underlying the development of HFpEF and should be investigated further.