PLoS One. 2017 Jun 15;12(6):e0179534

Bahls M, Groß S, Ittermann T, Busch R, Gläser S, Ewert
R, Völzke H, Felix SB, Dörr M

BACKGROUND: Exercise and statins reduce cardiovascular disease (CVD). Exercise
capacity may be assessed using cardiopulmonary exercise testing (CPET). Whether
statin medication is associated with CPET parameters is unclear. We investigated
if statins are related with exercise capacity during CPET in the general
population.
METHODS: Cross-sectional data of two independent cohorts of the Study of Health
in Pomerania (SHIP) were merged (n = 3,500; 50% males). Oxygen consumption (VO2)
at peak exercise (VO2peak) and anaerobic threshold (VO2@AT) was assessed during
symptom-limited CPET. Two linear regression models related VO2peak with statin
usage were calculated. Model 1 adjusted for age, sex, previous myocardial
infarction, and physical inactivity and model 2 additionally for body mass index,
smoking, hypertension, diabetes and estimated glomerular filtration rate.
Propensity score matching was used for validation.
RESULTS: Statin usage was associated with lower VO2peak (no statin: 2336;
95%-confidence interval [CI]: 2287-2,385 vs. statin 2090; 95%-CI: 2,031-2149
ml/min; P < .0001) and VO2@AT (no statin: 1,172; 95%-CI: 1,142-1,202 vs. statin:
1,111; 95%-CI: 1,075-1,147 ml/min; P = .0061) in males but not females (VO2peak:
no statin: 1,467; 95%-CI: 1,417-1,517 vs. statin: 1,503; 95%-CI: 1,426-1,579
ml/min; P = 1.00 and VO2@AT: no statin: 854; 95%-CI: 824-885 vs. statin 864;
95%-CI: 817-911 ml/min; P = 1.00). Model 2 revealed similar results. Propensity
scores analysis confirmed the results.
CONCLUSION: In the general population present statin medication was related with
impaired exercise capacity in males but not females. Sex specific effects of
statins on cardiopulmonary exercise capacity deserve further research

Pediatr Cardiol. 2017 Aug;38(6):1097-1105. doi: 10.1007/s00246-017-1656-z. Epub
2017 Jun 16.

Dallaire F, Wald RM, Marelli A.

Tetralogy of Fallot is the most common form of cyanotic congenital heart disease.
As a result of the surgical strategies employed at the time of initial repair,
chronic pulmonary regurgitation (PR) is prevalent in this population. Despite
sustained research efforts, patient selection and timing of pulmonary valve
replacement (PVR) to address PR in young asymptomatic patients with repaired
tetralogy of Fallot (rToF) remain a fundamental but as yet unanswered question in
the field of congenital heart disease. The ability of the heart to compensate for
the chronic volume overload imposed by PR is critical in the evaluation of the
risks and benefits of PVR. The difficulty in clarifying the functional impact of
PR on the cardiovascular capacity may be in part responsible for the uncertainty
surrounding the timing of PVR. Cardiopulmonary exercise testing (CPET) may be
used to assess abnormal cardiovascular response to increased physiologic demands.
However, its use as a tool for risk stratification in asymptomatic adolescents
and young adults with rToF is still ill-defined. In this paper, we review the
role of CPET as a potentially valuable adjunct to current risk stratification
strategies with a focus on asymptomatic rToF adolescents and young adults being
considered for PVR. The role of maximal and submaximal exercise measurements to
identify young patients with a decreased or borderline low peak VO2 resulting
from impaired ventricular function is explored. Current knowledge gaps and
research perspectives are highlighted.

PLoS One. 2017 Sep 14;12(9):e0183926

Rogan A, McCarthy K, McGregor G, Hamborg T, Evans G, Hewins
S, Aldridge N, Fletcher S, Krishnan N, Higgins R, Zehnder D,
Ting SM

BACKGROUND: Patients with advanced chronic kidney disease (CKD) experience
complex functional and structural changes of the cardiopulmonary and
musculoskeletal system. This results in reduced exercise tolerance, quality of
life and ultimately premature death. We investigated the relationship between
subjective measures of health related quality of life and objective, standardised
functional measures for cardiovascular and pulmonary health.
METHODS: Between April 2010 and January 2013, 143 CKD stage-5 or CKD5d patients
(age 46.0±1.1y, 62.2% male), were recruited prospectively. A control group of 83
healthy individuals treated for essential hypertension (HTN; age 53.2±0.9y,
48.22% male) were recruited at random. All patients completed the SF-36 health
survey questionnaire, echocardiography, vascular tonometry and cardiopulmonary
exercise testing.
RESULTS: Patients with CKD had significantly lower SF-36 scores than the HTN
group; for physical component score (PCS; 45.0 vs 53.9, p<0.001) and mental
component score (MCS; 46.9 vs. 54.9, p<0.001). CKD subjects had significantly
poorer exercise tolerance and cardiorespiratory performance compared with HTN
(maximal oxygen uptake; VO2peak 19.9 vs 25.0ml/kg/min, p<0.001). VO2peak was a
significant independent predictor of PCS in both groups (CKD: b = 0.35, p = 0.02
vs HTN: b = 0.27, p = 0.001). No associations were noted between PCS scores and
echocardiographic characteristics, vascular elasticity and cardiac biomarkers in
either group. No associations were noted between MCS and any variable. The
interaction effect of study group with VO2peak on PCS was not significant (ΔB =
0.08; 95%CI -0.28-0.45, p = 0.7). However, overall for a given VO2peak, the
measured PCS was much lower for patients with CKD than for HTN cohort, a likely
consequence of systemic uremia effects.
CONCLUSION: In CKD and HTN, objective physical performance has a significant
effect on quality of life; particularly self-reported physical health and
functioning. Therefore, these quality of life measures are indeed a good
reflection of physical health correlating highly with objective physical
performance measures.

Onofre T; Carlos R; Oliver N; Felismino A; Fialho D; Corte R; da Silva EP; Godoy E; Bruno S,

Obesity Surgery [Obes Surg], ISSN: 1708-0428, 2017 Aug; Vol. 27 (8), pp. 2026-2033; Publisher:
Springer Science + Business Media; PMID: 28386756;

Background:
In severely obese individuals, reducing body weight induced by bariatric
surgery is able to promote a reduction in comorbidities and improve
respiratory symptoms. However, cardiorespiratory fitness (CRF)
reflected by peak oxygen uptake (VO2peak) may not improve in
individuals who remain sedentary post-surgery. The objective of this
study was to evaluate the effects of a physical training program on CRF
and pulmonary function in obese women after bariatric surgery, and to
compare them to a control group.
Methods: Twelve obese female candidates for bariatric surgery were evaluated in the preoperative, 3 months
postoperative (3MPO), and 6 months postoperative (6MPO) periods through
anthropometry, spirometry, and cardiopulmonary exercise testing (CPX).
In the 3MPO period, patients were divided into control group (CG,
n = 6) and intervention group (IG, n = 6). CG received only general
guidelines while IG underwent a structured and supervised physical
training program involving aerobic and resistance exercises, lasting
12 weeks.
Results: All patients had a significant reduction in
anthropometric measurements and an increase in lung function after
surgery, with no difference between groups. However, only IG presented
a significant increase (p < 0.05) in VO2peak and total CPX duration of
5.9 mL/kg/min (23.8%) and 4.9 min (42.9%), respectively.Conclusions:
Applying a physical training program to a group of obese women after
3 months of bariatric surgery could promote a significant increase in
CRF only in the trained group, yet also showing that bariatric surgery
alone caused an improvement in the lung function of both groups.

Kahn SR; Akaberi A; Granton JT; Anderson DR; Wells PS; Rodger MA; Solymoss S; Kovacs MJ; Rudski L; Shimony A; Dennie C; Rush C; Hernandez P; Aaron SD; Hirsch AM,

The American Journal Of Medicine [Am J Med], ISSN: 1555-7162, 2017 Aug; Vol. 130 (8), pp.
990.e9-990.e21; Publisher: Excerpta Medica; PMID: 28400247;

Background:
We aimed to evaluate health-related quality of life (QOL), dyspnea, and
functional exercise capacity during the year following the diagnosis of
a first episode of pulmonary embolism.
Methods: This was a prospective
multicenter cohort study of 100 patients with acute pulmonary embolism
recruited at 5 Canadian hospitals from 2010-2013. We measured the
outcomes QOL (by Short-Form Health Survey-36 [SF-36] and Pulmonary
Embolism Quality of Life [PEmb-QoL] measures), dyspnea (by the
University of California San Diego Shortness of Breath Questionnaire
[SOBQ]) and 6-minute walk distance at baseline and 1, 3, 6, and 12
months after acute pulmonary embolism. Computed tomography pulmonary
angiography was performed at baseline, echocardiogram was performed
within 10 days, and cardiopulmonary exercise testing was performed at 1
and 12 months. Predictors of change in QOL, dyspnea, and 6-minute walk
distance were assessed by repeated-measures mixed-effects models
analysis.Results: Mean age was 50.0 years; 57% were male and 80% were
treated as outpatients. Mean scores for all outcomes improved during
1-year follow-up: from baseline to 12 months, mean SF-36 physical
component score improved by 8.8 points, SF-36 mental component score by
5.3 points, PEmb-QoL by -32.1 points, and SOBQ by -16.3 points, and
6-minute walk distance improved by 40 m. Independent predictors of
reduced improvement over time were female sex, higher body mass index,
and percent-predicted VO2 peak <80% on 1 month cardiopulmonary exercise
test for all outcomes; prior lung disease and higher pulmonary artery
systolic pressure on 10-day echocardiogram for the outcomes SF-36
physical component score and dyspnea score; and higher main pulmonary
artery diameter on baseline computed tomography pulmonary angiography
for the outcome PEmb-QoL score.Conclusions: On average, QOL, dyspnea,
and walking distance improve during the year after pulmonary embolism.
However, a number of clinical and physiological predictors of reduced
improvement over time were identified, most notably female sex, higher
body mass index, and exercise limitation on 1-month cardiopulmonary
exercise test. Our results provide new information on patient-relevant
prognosis after pulmonary embolism.

Le VD; Jensen GV; Kjøller-Hansen L,

The American Journal Of Cardiology [Am J Cardiol], ISSN: 1879-1913, 2017 Sep 01; Vol. 120 (5), pp. 844-849;
Publisher: Excerpta Medica; PMID: 28705379;

The approach to managing
asymptomatic or questionably symptomatic patients for aortic stenosis
is difficult. We aimed to determine whether cardiopulmonary exercise
testing (CPET) is prognostically useful in such patients. Patients
judged asymptomatic or questionably symptomatic for aortic stenosis
with aortic valve area index <0.6 cm2/m2 and left ventricular ejection
fraction ≥0.50 were managed conservatively provided they had either
(group 1) normal peak oxygen consumption and peak oxygen pulse (>83%
and >95% of the predicted values, respectively) or (group 2) subnormal
peak oxygen consumption or peak oxygen pulse but with CPET data
pointing to pathologies other than hemodynamic compromise from aortic
stenosis. Increase in systolic blood pressure <20 mm Hg, ST
depression ≥2 mm, or symptoms during the exercise test were allowed.
Unexpected events included cardiac death or hospitalization with heart
failure in patients who had not been recommended valve replacement. The
median age of the study population (n = 101) was 75 years
(interquartile range 65 to 79 years), and 67% were judged questionably
symptomatic. During a follow-up at 24 ± 6 months, the rate of
unexpected cardiac death and unexpected hospitalization with heart
failure was 0% and 6.0%, respectively. All-cause mortality was 4.0%
compared with 8.0% in the age- and gender-matched population. For group
1, 26 of 70 (37.1%) succumbed to cardiac death, or were hospitalized
because of heart failure, or underwent valve replacement, and for group
2 this was 12 of 31 (38.7%). In conclusion, if CPET does not indicate a
significant hemodynamic compromise because of aortic stenosis, an
initially conservative strategy results in a good prognosis and an
acceptable event rate.

Trankle, C., Canada, J. M., Buckley, L., Carbone, S., Dixon, D., Arena, R., Van Tassell, B., Abbate, A.

ESC Heart Fail. 2017;4(3):351-355.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by impaired exercise capacity due to shortness of breath and/or fatigue. Assessment of diastolic dysfunction at rest and with exercise may provide insight into the pathophysiology of exercise intolerance in HFpEF.
AIMS: To measure echocardio-Doppler-derived parameters of diastolic function as they relate to various indices of aerobic exercise capacity in HFpEF.
METHODS: We selected 16 subjects with clinically stable HFpEF, no evidence of volume overload, but impaired functional capacity by cardiopulmonary exercise testing [peak oxygen consumption (VO2 )]. We measured the transmitral E and A flow velocities, E/A ratio, and E deceleration time (DT) and tissue Doppler E’ velocity. We also indexed the E’ to the DT, as additional measure of impaired relaxation (E’DT ), and calculated the diastolic functional reserve index (DFRI), as the product of E’ at rest and change in E’ with exercise.
RESULTS: E’ velocity, at rest and peak exercise, as well as the DFRI positively correlated with peak VO2 , whereas DT, E’DT , and E/E’ with exercise inversely correlated with peak VO2 . Of note, the E’DT at rest also significantly predicted E’ velocity at peak exercise (R = +0.81, P < 0.001). Exercise E’ was the only independent predictor of peak VO2 at multivariable analysis (R = +0.67, P = 0.005).
CONCLUSIONS: The E’ velocity at peak exercise is a strong and independent predictor of aerobic exercise capacity as measured by peak VO2 in patients with HFpEF, providing the link between abnormal myocardial relaxation with exercise and impaired aerobic exercise capacity in HFpEF.

Shen L, Jhund PS, Petrie MC, et al.

N Engl J Med. 2017;377(1):41-51.

BACKGROUND: The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail.
METHODS: We analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014. Patients who had an implantable cardioverter-defibrillator at the time of trial enrollment were excluded. Weighted multivariable regression was used to examine trends in rates of sudden death over time. Adjusted hazard ratios for sudden death in each trial group were calculated with the use of Cox regression models. The cumulative incidence rates of sudden death were assessed at different time points after randomization and according to the length of time between the diagnosis of heart failure and randomization.
RESULTS: Sudden death was reported in 3583 patients. Such patients were older and were more often male, with an ischemic cause of heart failure and worse cardiac function, than those in whom sudden death did not occur. There was a 44% decline in the rate of sudden death across the trials (P=0.03). The cumulative incidence of sudden death at 90 days after randomization was 2.4% in the earliest trial and 1.0% in the most recent trial. The rate of sudden death was not higher among patients with a recent diagnosis of heart failure than among those with a longer-standing diagnosis.
CONCLUSIONS: Rates of sudden death declined substantially over time among ambulatory patients with heart failure with reduced ejection fraction who were enrolled in clinical trials, a finding that is consistent with a cumulative benefit of evidence-based medications on this cause of death. (Funded by the China Scholarship Council and the University of Glasgow.).

ESC Heart Fail. 2017 Aug;4(3):351-355. doi: 10.1002/ehf2.12147. Epub 2017 May 6.

Trankle C, Canada JM, Buckley L, Carbone S, Dixon D, Arena
R, Van Tassell B, Abbate A

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a clinical
syndrome characterized by impaired exercise capacity due to shortness of breath
and/or fatigue. Assessment of diastolic dysfunction at rest and with exercise may
provide insight into the pathophysiology of exercise intolerance in HFpEF.
AIMS: To measure echocardio-Doppler-derived parameters of diastolic function as
they relate to various indices of aerobic exercise capacity in HFpEF.
METHODS: We selected 16 subjects with clinically stable HFpEF, no evidence of
volume overload, but impaired functional capacity by cardiopulmonary exercise
testing [peak oxygen consumption (VO2 )]. We measured the transmitral E and A
flow velocities, E/A ratio, and E deceleration time (DT) and tissue Doppler E’
velocity. We also indexed the E’ to the DT, as additional measure of impaired
relaxation (E’DT ), and calculated the diastolic functional reserve index (DFRI),
as the product of E’ at rest and change in E’ with exercise.
RESULTS: E’ velocity, at rest and peak exercise, as well as the DFRI positively
correlated with peak VO2 , whereas DT, E’DT , and E/E’ with exercise inversely
correlated with peak VO2 . Of note, the E’DT at rest also significantly predicted
E’ velocity at peak exercise (R = +0.81, P < 0.001). Exercise E’ was the only
independent predictor of peak VO2 at multivariable analysis (R = +0.67,
P = 0.005).
CONCLUSIONS: The E’ velocity at peak exercise is a strong and independent
predictor of aerobic exercise capacity as measured by peak VO2 in patients with
HFpEF, providing the link between abnormal myocardial relaxation with exercise
and impaired aerobic exercise capacity in HFpEF..

Pediatr Cardiol. 2017 Aug 3. doi: 10.1007/s00246-017-1697-3. [Epub ahead of
print]

Meierhofer C, Tavakkoli T, Kühn A, Ulm K, Hager A, Müller J,
Martinoff S, Ewert P, Stern H.

Good quality of life correlates with a good exercise capacity in daily life in
patients with tetralogy of Fallot (ToF). Patients after correction of ToF usually
develop residual defects such as pulmonary regurgitation or stenosis of variable
severity. However, the importance of different hemodynamic parameters and their
impact on exercise capacity is unclear. We investigated several hemodynamic
parameters measured by cardiovascular magnetic resonance (CMR) and
echocardiography and evaluated which parameter has the most pronounced effect on
maximal exercise capacity determined by cardiopulmonary exercise testing (CPET).
132 patients with ToF-like hemodynamics were tested during routine follow-up with
CMR, echocardiography and CPET. Right and left ventricular volume data,
ventricular ejection fraction and pulmonary regurgitation were evaluated by CMR.
Echocardiographic pressure gradients in the right ventricular outflow tract and
through the tricuspid valve were measured. All data were classified and
correlated with the results of CPET evaluations of these patients. The analysis
was performed using the Random Forest model. In this way, we calculated the
importance of the different hemodynamic variables related to the maximal oxygen
uptake in CPET (VO2%predicted). Right ventricular pressure showed the most
important influence on maximal oxygen uptake, whereas pulmonary regurgitation and
right ventricular enddiastolic volume were not important hemodynamic variables to
predict maximal oxygen uptake in CPET. Maximal exercise capacity was only very
weakly influenced by right ventricular enddiastolic volume and not at all by
pulmonary regurgitation in patients with ToF. The variable with the most
pronounced influence was the right ventricular pressure.