Jain B, All India Institute of Medical Sciences, New Delhi, INDIA
Chakrawarty A, Chatterjee P, Dey AB, Khan M

Cureus. 2026 Apr 26;18(4):e107740. doi: 10.7759/cureus.107740. eCollection 2026 Apr.

Background Frailty, intrinsic capacity (IC), and cardiorespiratory fitness each reflect physiological reserve in aging, yet integrated data combining standardized cardiopulmonary exercise testing (CPET) with the World Health Organization (WHO) Integrated Care for Older People (ICOPE) framework and the Fried phenotype are scarce, particularly in South Asian older adults, where the burden of chronic disease may accelerate functional decline.
Methods This cross-sectional study included 130 healthcare-seeking adults aged ≥65 years attending a tertiary geriatric outpatient clinic in India. Frailty was assessed using the Fried phenotype, intrinsic capacity using the World Health Organization Integrated Care for Older People framework across five domains, and cardiorespiratory fitness using CPET to determine maximal oxygen uptake (VO₂max). Associations between IC, frailty, and VO₂max were examined using univariate and multivariable linear regression analyses.
Results Frailty prevalence was 73.1% (95/130 participants). Frail participants demonstrated significantly lower skeletal muscle mass, poorer functional performance, and reduced cardiorespiratory fitness compared with non-frail individuals. Higher IC impairment scores were associated with older age, poorer anthropometric measures, reduced physical performance, and lower absolute VO₂max (all p < 0.05). In univariate analyses, several variables, including age, skeletal muscle mass, handgrip strength, gait speed, physical activity, and IC domains, were associated with VO₂max. In a prespecified multivariable regression model adjusting for age, sex, and frailty status, IC total score remained independently associated with lower absolute VO₂max (β ≈ -31 mL/min per point, p ≈ 0.03). Frailty demonstrated a borderline association but did not retain statistical significance after adjustment.
Conclusions Impairment of intrinsic capacity was independently associated with lower cardiorespiratory fitness in older adults, independent of age, sex, and frailty status. These cross-sectional findings are hypothesis-generating, and prospective studies are required to determine whether intrinsic capacity precedes decline in aerobic fitness and frailty. Integrating intrinsic capacity assessment with objective measures of aerobic fitness may improve early identification of vulnerable older adults and inform preventive geriatric care strategies.

Guerra E; Carlo Poma Hospital, Mantova, Italy.
Segreti A; Carpenito M; Ciancio M; Guarino L; Ricciardi D; Fossati C; Suma S; Gaibazzi N;
Rosiello R; Lettieri C; Papalia R; Pigozzi F; Boriani G; Grigioni F

Echocardiography. 43(5):e70505, 2026 May.

PURPOSE: This study investigated standard and advanced echocardiographic
parameters in endurance athletes with different training profiles, and
their association with exercise performance.

METHODS: Consecutive endurance athletes undergoing cardiological
screening or orthopedic evaluation for knee injuries at Campus Bio-Medico
University Hospital underwent advanced echocardiography and
cardiopulmonary exercise testing. Athletes were categorized into three
groups: (1) Long-Distance (marathon and ultramarathon runners, n = 30);
(2) Mid-Distance (middle-distance runners, n = 27); and (3) Detrained (>=
6 months training interruption, n = 31).

RESULTS: Left ventricular ejection fraction did not differ among groups.
The Long-Distance group had the highest stroke volume index, followed by
the Mid-Distance and Detrained groups (p <0.001). Long-Distance athletes
showed lower left ventricular global longitudinal strain (p = 0.003) and
left atrial reservoir strain (p = 0.003) compared to the other groups,
with no differences in right ventricular free wall strain. Myocardial work
analysis showed higher work index and constructive work, and lower wasted
work, leading to greater global work efficiency in the Long-Distance group
(p <0.001). In multivariable linear regression analysis, stroke volume
index (beta = 1.02, p < 0.001) and global work efficiency (beta = 1.00, p
= 0.001) were independently associated with Peak VO2, whereas global
longitudinal strain was not.

CONCLUSION: Advanced echocardiography provides additional insights into
the athlete’s heart. Myocardial work indices reflect training-related
cardiac adaptations, and left atrial reservoir strain is influenced by
training status. These findings, together with the association of stroke
volume index and global work efficiency with Peak VO2, support the
integration of advanced echocardiographic parameters into athlete
evaluation and monitoring.

Martinez-Otero S; Department of Anaesthesia and ICU, Hospital Clinic de Barcelona, Spain.
Gimenez-Mila M; Arguis MJ; Regueiro A; Rodriguez-Arias
JJ; Sanz de la Garza M; Berenguel A; Gadella A; Kenneally LF;
Martinez-Palli G

PLoS ONE [Electronic Resource]. 21(5):e0348568, 2026.

INTRODUCTION: Transcatheter Aortic Valve Implantation (TAVI) has emerged
as a less invasive alternative to surgical aortic valve replacement,
especially for high-risk patients. While TAVI is expected to improve
symptoms and functional status, clinical recovery is often heterogeneous,
and subjective assessments may not fully capture the degree of
improvement. To our knowledge, the changes in functional capacity
following TAVI have not been well explored using cardiopulmonary exercise
testing (CPET). The study aims to characterise mid-term changes in
exercise tolerance after TAVI and identify clinical and functional
predictors of improvement in exercise capacity and complications after
TAVI.

METHODS AND ANALYSIS: A total of 161 patients with severe aortic stenosis
scheduled for TAVI will be prospectively enrolled across three expert
centres. Each will undergo clinical assessment and incremental CPET within
two weeks before and four to six weeks after the procedure. The primary
outcome is a change in VO2 peak and VO2 at the anaerobic threshold.
Secondary outcomes include exploratory associations between baseline
characteristics and observed changes in functional capacity, quality of
life and complications.

ETHICS AND DISSEMINATION: The bioethics committee of the Hospital Clinic
de Barcelona, Spain, approved this protocol (HCB/2024/0782). All the
participating centres obtained local approval prior to patient
recruitment. The findings will be published in a peer-reviewed journal and
submitted to relevant conferences.

Janssens K; St. Vincent’s Institute of Medical Research, Fitzroy, Australia.
Howden EJ; Mitchell AM; Wright L; Climie RE; Parr EB;
Haykowsky MJ; La Gerche A; Foulkes SJ

American Journal of Physiology – Heart & Circulatory Physiology.
330(6):H1841-H1852, 2026 Jun 01.

During exercise, vascular resistance, the ratio of arterial pressure to
blood flow [i.e., cardiac output (CO)], is an important component of the
hemodynamic response determining peak oxygen uptake (Vo2peak). However,
how systolic blood pressure (SBP) responses reflect this pressure-flow
relationship, and their association with Vo2peak remain incompletely
understood. We performed cardiopulmonary exercise testing in 135 females
(51 +/- 8 yr) across a broad fitness spectrum to evaluate Vo2peak and SBP
responses. SBP responses were stratified by maximal SBP (SBPmax <190 mmHg
or >=190 mmHg) and workload-indexed SBP (SBP/W-slope; low vs. high based
on sex- and age-specific median values). Peak CO (COpeak) was quantified
from exercise cardiac magnetic resonance imaging. SBPmax >=190 mmHg
occurred in 74 participants (55%), high SBP/W-slope in 41 (30%), and 26
(19%) had both. A high SBP/W-slope was associated with lower Vo2peak (1.7
+/- 0.4 vs. 2.1 +/- 0.6 L/min; P < 0.001) and COpeak (12.8 +/- 2.3 vs.
15.7 +/- 3.5 L/min; P < 0.001) and higher total peripheral resistance
(TPRpeak; 11.2 +/- 2.3 vs. 9.0 +/- 2.0 mmHg.min/L; P < 0.001). In
contrast, a low SBP/W-slope despite SBPmax >=190 mmHg had the highest
Vo2peak and COpeak and larger reductions in TPR compared with high
SBP/W-slope groups. SBPmax >=190 mmHg in isolation was associated with
higher Vo2peak and COpeak, although it also identified females with low
fitness and COpeak. Thus, SBP/W-slope provides a framework for
interpreting SBP relative to flow, with higher slopes indicating an
unfavorable pressure-flow profile characterized by higher vascular
resistance, lower COpeak, and reduced Vo2peak. In contrast, SBPmax
reflects both flow and resistance. Incorporating SBP/W-slope may therefore
improve identification of females with impaired pressure-flow regulation.
NEW & NOTEWORTHY In females, a higher workload-indexed systolic blood
pressure (SBP/W)-slope during exercise was associated with greater
peripheral vascular resistance, lower cardiac output, and lower
cardiorespiratory fitness, irrespective of maximal systolic blood pressure
(SBPmax). In contrast, an exaggerated SBPmax alone reflected differing
contributions of increased flow (i.e., cardiac output) or increased
vascular resistance across individuals. Evaluating the SBP/W-slope
provides a more physiologically informed interpretation of exercise blood
pressure and may improve identification of females with impaired
pressure-flow regulation and reduced cardiovascular reserve.

Mielniczuk M; National Research Institute, Warsaw, Poland.
Krzesinski P; Uzieblo-Zyczkowska B; Kwiatkowski P; Kowal J;
Dziuk M; Wlochacz A; Maciorowska M; Malinowski M; Banak M; Surmacz E;
Gielerak G

Cardiology Journal. 33:e00226055, 2026.

BACKGROUND: Chronic total occlusion (CTO) is a common finding on coronary
angiograms of patients diagnosed with coronary artery disease, with an
incidence ranging from 15 to 25%. Despite its high incidence, this type of
coronary lesion is rarely treated with percutaneous coronary intervention.
The key to success appears to be appropriate qualification for
revascularization. Asymptomatic patients should be assessed for inducible
ischemia within the occluded vessel territory to detect patients with a
high ischemic burden, defined as inducible ischemia involving > 10% of the
myocardium. Single-photon emission computed tomography (SPECT) is a
well-established method of myocardial perfusion assessment; however, it is
not widely available, especially in less developed regions. The aim of the
study was to evaluate CTO patients to identify clinical parameters that
could predict the presence of relevant inducible ischemia measured by
SPECT.

METHODS: The study included 50 patients with a single-vessel CTO and
without any other significant coronary artery stenosis. Patients underwent
clinical examination, laboratory tests, echocardiography, 6-minute walk
test, cardiopulmonary exercise testing, exercise impedance cardiography,
and SPECT.

RESULTS: The only parameters associated with a high ischemic burden were
CTO location (in the left anterior descending artery and circumflex
artery) and one echocardiographic parameter: myocardial lateral wall
longitudinal strain.

CONCLUSIONS: Given the high incidence of CTO, there is an increasing need
to define non-invasive markers that could predict the presence of a high
ischemic burden and good clinical outcome after revascularization.
Echocardiographic longitudinal strains are worth further research in terms
of their utility in predicting inducible ischemia.

Koble K; Technical University Munich, Munchen, Germany.
Willinger L; Engl T; Muhlbauer F; Huber S; Dettenhofer M;
Oberhoffer R

International journal of sports physiology & performance. 21(6):748-757,
2026 Jun 01.

PURPOSE: While the development of cardiorespiratory fitness in normally
active children and adolescents is well-documented, longitudinal data on
physiological adaptations to training in youth athletes remain limited.
This study aimed to investigate the long-term development of
cardiorespiratory fitness in young competitive athletes over a period of
2-6 years.

METHODS: A total of 397 young athletes (48 girls), aged 8-20 years, from
a variety of sports underwent up to 6 repeated assessments between 2012
and 2024. Peak exercise performance (Wmax) and peak aerobic power
(VO2peak), both were measured via cardiopulmonary exercise testing on an
electronically braked cycle ergometer. A linear mixed model analysis was
used to evaluate longitudinal changes in VO2peak and Wmax (both normalized
to body mass), including body surface area and training intensity
(MET-hours/week) as fixed effects, with sex-stratified analyses.

RESULTS: A total of 1009 cardiopulmonary exercise testing were analyzed.
At baseline, boys showed higher age-specific VO2peak and Wmax, while girls
had higher age-specific VO2peak despite similar training intensity.
Longitudinally, VO2peak increased significantly with age in mid-adolescent
girls and boys, particularly in endurance athletes, and was positively
associated with training intensity. Wmax rose with age but was less
influenced by training or sport type, showing a stronger relationship with
growth-related factors like body surface area.

CONCLUSIONS: VO2peak development in youth athletes is influenced by age,
body size, training intensity, and sport type, making it a sensitive
marker of aerobic adaptation. In contrast, Wmax reflects primarily
maturational growth and is less responsive to training-specific factors.

Huang R;  Guangzhou Medical University, China.
Deng Y; Li M; Chen L; Lv M; Liao L; Ma L; Huang Z

Trials [Electronic Resource]. 27(1), 2026 Apr 07.

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF)
constitutes nearly half of patients with heart failure, but there is still
a lack of treatment options to improve prognosis. Empagliflozin is a new
hypoglycemic medication classified as sodium glucose cotransporter 2
inhibitors (SGLT2i); nonetheless, its effects on exercise tolerance in
HFpEF remain ambiguous. Additional clinical studies are necessary to
clarify the effect of SGLT2i in HFpEF. This study aims to evaluate the
efficacy and safety of empagliflozin on exercise tolerance in patients
with heart failure with preserved ejection fraction without diabetes,
using cardiopulmonary exercise testing.

METHODS AND ANALYSIS: This study is a single-center, open-label,
randomized controlled trial. We will randomly (1:1) assign 86 patients
with an ejection fraction of more than 40% and class II-III heart failure
to receive empagliflozin (10 mg once daily) or to maintain their original
treatment regimen. The treatment duration will be 12 weeks. The primary
endpoint is the evaluation of changes in peak oxygen uptake (peak VO2)
after a 12-week period using cardiopulmonary exercise testing (CPET). The
secondary endpoints encompassed additional parameters of CPET and
echocardiography, N-terminal pro-B-type natriuretic peptide level, alanine
aminotransferase level, aspartate transaminase level, estimated glomerular
filtration rate level, New York Heart Association functional
classification, and scores from the Minnesota Living with Heart Failure
Questionnaire. Safety events associated with empagliflozin and CPET will
be monitored.

DISCUSSION: We used peak oxygen uptake, the gold standard for assessing
exercise tolerance, to evaluate the efficacy and safety of empagliflozin
in treating non-diabetic patients with HFpEF. The improvement in quality
of life of heart failure patients by SGLT2i will be objectively assessed.

Heinz V;  University Medicine Berlin, Berlin, Germany.
Pilz N; Fesseler L; Lindner T; Malotka L; Opatz O; Blottner D;
Anosov O; Patzak A; Fahling M; Bothe TL

Scientific Reports. 16(1), 2026 May 19.
Headings by Dr Older

Background A ubiquitously available and accurate non-invasive ventilatory threshold
assessment (NIVA) would substantially improve real-world performance
assessment evaluation in both clinical and elite sports settings. We
hypothesised that ECG-derived ventilatory phase analysis achieves
reference-standard accuracy for second ventilatory threshold (VT2)
determination.
Methods 74 healthy adults performed stepwise cardiopulmonary
exercise testing with simultaneous lactate sampling to retrieve VT2 and
lactate-based (Dmax; LT2) thresholds. Threshold agreement was evaluated
for heart rate (HR) and exercise load (W) between VT2, LT2, age-estimated
HR (HR-Est) and NIVA.
Results In 66 assessable datasets, NIVA and VT2 yielded
equivalent threshold estimates for HR (- 0.46 bpm; 90% CI [- 2.10;1.17])
and exercise load (0.46 W; 90% CI [- 2.35; 3.27]). VT2 and HR-Est diverged
(HR – 7.22 bpm, p < 0.001; load – 6.26 W; p < 0.001). LT2 was available in
58 subjects and differed from both VT2 (p < 0.001) and NIVA (p < 0.001).
Correlations supported these findings, with close associations between VT2
and NIVA (HR r = 0.84; load r = 0.96). NIVA derived a high-intensity
performance threshold from ECG signals with reference-standard fidelity
and showed close agreement with CPET-derived VT2.
Conclusions Its performance and
accessibility make it attractive for frequent reassessment of a
VT2-aligned threshold without the need for spiroergometry or lactate
measurements. Validation across devices, protocols, populations, and
real-world signal conditions is warranted.

Lyons S;  Department of Neurology, University Hospital Waterford, Ireland.
Kearney M; Fahey MC; Janjal P; Pandolfo M; Patton P

Cochrane Database of Systematic Reviews. 5:CD007791, 2026 05 12.VI 1

RATIONALE: Friedreich ataxia (FRDA) is a rare inherited autosomal
recessive neurological disorder, characterised initially by unsteadiness
in standing and walking, and slowly progressing to wheelchair dependency,
usually in the late teens or early twenties. Scoliosis, pes cavus and
cardiomyopathy are often present at diagnosis. As the disease progresses,
individuals usually develop slurred speech, auditory impairment
(especially in a noisy environment), urinary tract morbidity, diabetes,
anxiety, depression, muscle spasticity and visual disturbances. Cardiac
abnormalities cause premature death in 60% of people with FRDA. There is
no easily defined clinical or biochemical marker to assess progression and
no known curative treatment. This is the third update of a review
published in 2009 and updated in 2012 and 2016.

OBJECTIVES: To assess the effects of pharmacological treatments for
people with Friedreich ataxia (FRDA) after 12 months of treatment.

SEARCH METHODS: To identify studies for inclusion in this review, we
searched CENTRAL, MEDLINE, Embase, CINAHL Plus, TRIP, Orphanet, WHO
International Clinical Trials Registry Platform (ICTRP) and
ClinicalTrials.gov. We also checked reference lists of relevant studies
and contacted study authors. The most recent search was on 4 February
2025.

ELIGIBILITY CRITERIA: We were interested in randomised controlled trials
(RCTs) and quasi-RCTs of pharmacological treatments (including vitamins)
in people with genetically-confirmed FRDA. To be included in the review,
studies had to last at least 12 months.

OUTCOMES: We assessed the following outcomes after 12 months of
treatment: change in score on a validated ataxia rating scale; change in
interventricular septal thickness in diastole (IVSTd) by cardiac magnetic
resonance imaging or echocardiogram; change in activities of daily living
(ADL) using a validated questionnaire; change in upper limb dexterity; and
change in cardiopulmonary exercise testing (CPET). We also assessed
treatment-related adverse events with medication continued for the study
period, and treatment-emergent adverse events leading to cessation of
medication or death during the study period.

RISK OF BIAS: Using the Cochrane risk of bias tool RoB 2, we assessed the
risk of bias in the seven outcomes reported in our summary of findings
tables.

SYNTHESIS METHODS: We synthesised the results of the studies for each
outcome using meta-analysis, where possible. We calculated the mean
difference (MD) or standardised mean difference (SMD) for continuous
outcomes, and the risk ratio (RR) for dichotomous outcomes, all with 95%
confidence intervals (CIs). We used GRADE to assess the certainty of
evidence for our prespecified outcomes as high, moderate, low or very low.

INCLUDED STUDIES: We included eight RCTs in this updated review. We
included seven of them in meta-analysis, and these studies enroled a total
of 574 participants, with sample sizes ranging from 29 to 232 participants
per study. One study was international, with centres in North America,
Europe and Australia. There were four other multicentre studies (three in
Europe and one in North America). Single-centre studies were conducted in
the UK, Italy and France. Participants in the studies ranged from eight to
70 years of age at enrolment, with the mean age in each study being
between 18 years and 35 years (with an unweighted pooled mean age across
studies of 25.9 years). All of the studies enroled both males and females,
with the proportion of female participants ranging from 21% to 58%.
Sixty-eight per cent of participants had severe ataxia, while the other
32% had moderate ataxia. The studies tested epoetin alpha, CoQ10 and
vitamin E, idebenone, leriglitazone, omaveloxolone, and RT001. One study
tested pioglitazone but has not published any results. Four of the studies
were pharmaceutical-industry-controlled.

RATIONALE: Friedreich ataxia (FRDA) is a rare inherited autosomal
recessive neurological disorder, characterised initially by unsteadiness
in standing and walking, and slowly progressing to wheelchair dependency,
usually in the late teens or early twenties. Scoliosis, pes cavus and
cardiomyopathy are often present at diagnosis. As the disease progresses,
individuals usually develop slurred speech, auditory impairment
(especially in a noisy environment), urinary tract morbidity, diabetes,
anxiety, depression, muscle spasticity and visual disturbances. Cardiac
abnormalities cause premature death in 60% of people with FRDA. There is
no easily defined clinical or biochemical marker to assess progression and
no known curative treatment. This is the third update of a review
published in 2009 and updated in 2012 and 2016.

OBJECTIVES: To assess the effects of pharmacological treatments for
people with Friedreich ataxia (FRDA) after 12 months of treatment.

SEARCH METHODS: To identify studies for inclusion in this review, we
searched CENTRAL, MEDLINE, Embase, CINAHL Plus, TRIP, Orphanet, WHO
International Clinical Trials Registry Platform (ICTRP) and
ClinicalTrials.gov. We also checked reference lists of relevant studies
and contacted study authors. The most recent search was on 4 February
2025.

ELIGIBILITY CRITERIA: We were interested in randomised controlled trials
(RCTs) and quasi-RCTs of pharmacological treatments (including vitamins)
in people with genetically-confirmed FRDA. To be included in the review,
studies had to last at least 12 months.

OUTCOMES: We assessed the following outcomes after 12 months of
treatment: change in score on a validated ataxia rating scale; change in
interventricular septal thickness in diastole (IVSTd) by cardiac magnetic
resonance imaging or echocardiogram; change in activities of daily living
(ADL) using a validated questionnaire; change in upper limb dexterity; and
change in cardiopulmonary exercise testing (CPET). We also assessed
treatment-related adverse events with medication continued for the study
period, and treatment-emergent adverse events leading to cessation of
medication or death during the study period.

RISK OF BIAS: Using the Cochrane risk of bias tool RoB 2, we assessed the
risk of bias in the seven outcomes reported in our summary of findings
tables.

SYNTHESIS METHODS: We synthesised the results of the studies for each
outcome using meta-analysis, where possible. We calculated the mean
difference (MD) or standardised mean difference (SMD) for continuous
outcomes, and the risk ratio (RR) for dichotomous outcomes, all with 95%
confidence intervals (CIs). We used GRADE to assess the certainty of
evidence for our prespecified outcomes as high, moderate, low or very low.

INCLUDED STUDIES: We included eight RCTs in this updated review. We
included seven of them in meta-analysis, and these studies enroled a total
of 574 participants, with sample sizes ranging from 29 to 232 participants
per study. One study was international, with centres in North America,
Europe and Australia. There were four other multicentre studies (three in
Europe and one in North America). Single-centre studies were conducted in
the UK, Italy and France. Participants in the studies ranged from eight to
70 years of age at enrolment, with the mean age in each study being
between 18 years and 35 years (with an unweighted pooled mean age across
studies of 25.9 years). All of the studies enroled both males and females,
with the proportion of female participants ranging from 21% to 58%.
Sixty-eight per cent of participants had severe ataxia, while the other
32% had moderate ataxia. The studies tested epoetin alpha, CoQ10 and
vitamin E, idebenone, leriglitazone, omaveloxolone, and RT001. One study
tested pioglitazone but has not published any results. Four of the studies
were pharmaceutical-industry-controlled.