Author Archives: Paul Older

Clinical Evaluation of Microneedle Biosensors for Continuous Lactate Monitoring in Critically Ill Patients.

Djassemi O; Department of Bioengineering,San Diego, USA
Chang AY; McGuire WC; Mitchell E;

ACS Sensors. 11(2):1413-1424, 2026 Feb 27. VI 1

management of sepsis, shock, and metabolic stress, yet current serum
assays remain invasive, intermittent, and resource-intensive. We present a
clinical evaluation of a minimally invasive microneedle-based
electrochemical biosensor for real-time interstitial fluid (ISF) lactate
monitoring. The microneedle biosensor features a platinum working
electrode modified with a lactate oxidase reagent layer and a polyvinyl
chloride anti-fouling membrane for H2O2-mediated amperometry, toward
highly selective and stable ISF lactate detection. In a pilot study of
twenty-one participants across an intensive care unit, emergency
department, cardiopulmonary exercise testing, and controlled laboratory
settings, two enzyme-based microneedle sensors placed on the forearm and
thigh continuously tracked lactate for 4 h. Sensor performance
demonstrated strong agreement with blood lactate assays (r = 0.94), high
diagnostic accuracy for hyperlactatemia (>4 mmol/L; receiver operating
characteristic analysis, area under the curve = 0.95), and minimal bias
(-0.028 mmol/L) over a wide dynamic range (0.7-22.9 mmol/L) with high
selectivity against interferents. No significant ISF-blood differences (p
> 0.05) or adverse events were observed. These findings establish
microneedle biosensors as a promising platform for precision medicine,
with considerable potential to transform sepsis care, guide resuscitation,
and improve assessment of exertional dyspnea.

Comprehensive Assessment of Left Ventricular Function and Exercise Endurance in Patients with Hypertrophic Cardiomyopathy: The Combined Application of Left Ventricular Pressure-Strain Loop and Cardiopulmonary Exercise Testing.

Lin Y; Department of Ultrasound, Fujian Medical University, Longyan, China.
Hou S; Lin J; Zhang T et al

Cardiology. 151(4):458-470, 2026. VI 1

Introduction: This study aims to assess left ventricular (LV) function and
exercise endurance in patients with hypertrophic cardiomyopathy (HCM)
using a combination of left ventricular pressure-strain loop (LV-PSL) and
cardiopulmonary exercise testing (CPET) and to explore the correlation of
the maximum left ventricular wall thickness (MWT) with clinical,
echocardiographic, and CPET parameters.

METHODS: A total of 55 patients with nonobstructive HCM, diagnosed
between January 2022 and March 2023 at Longyan First Affiliated Hospital
of Fujian Medical University, were included, along with 55 healthy
volunteers as a control group. Two-dimensional ultrasound speckle tracking
technology was used to obtain global longitudinal strain (GLS),
longitudinal strain peak time dispersion (PSD), as well as the myocardial
global work index (GWI), myocardial global constructive work (GCW), global
wasted work (GWW), and global work efficiency (GWE). The differences in
these parameters were compared between the two groups before and after
CPET. CPET was used to measure peak oxygen consumption (Peak VO2),
anaerobic threshold (AT), ventilation equivalent for carbon dioxide slope
(VE/VCO2 slope), oxygen pulse (VO2/HR), and metabolic equivalents (METs),
and the differences between the two groups were also compared.

RESULTS: Compared to the control group, the HCM group showed significant
reductions in GLS, GWI, GCW, and GWE, while GWW and PSD were significantly
increased, with statistical significance (p < 0.05). Peak VO2, AT, VO2/HR,
and METs were significantly lower in the HCM group compared to the control
group, while VE/VCO2 slope did not show a significant increase (p > 0.05).
CPET, GWI, and GCW did not increase significantly in the HCM group (p >
0.05), whereas GWW and PSD showed significant increases (p < 0.05). In
contrast, in the control group, GWI and GCW increased significantly after
CPET (p < 0.05), and no significant changes were observed in GWW and PSD
(p > 0.05). Univariable linear regression analysis showed that MWT was
correlated with NYHA class, GLS, PSD, GCW, GWW, Peak VO2, and AT (p <
0.05). Multivariate linear regression analysis confirmed the independent
associations of MWT with PSD, GCW, and GWW (p < 0.05).

CONCLUSION: LV-PSL combined with CPET is effective in early detection of
LV function and exercise endurance impairment in HCM

Left ventricular rehabilitation after Ross operation for critical aortic stenosis with endocardial fibroelastosis.

Jacob KA; Department of Pediatric Cardiac Surgery, Utrecht, the Netherland
Korsuize NA; van Wijk A; Slieker MG; et al

Journal of Thoracic & Cardiovascular Surgery. 172(4):1074-1082.e2, 2026  Vol 1 Oct.

OBJECTIVES: Congenital critical aortic stenosis is frequently accompanied
by endocardial fibroelastosis (EFE), impairing diastolic compliance and
long-term ventricular performance. An early Ross procedure, with or
without concomitant EFE resection may restore left ventricular (LV)
function; however, long-term functional outcomes remain poorly
characterized. We evaluated long-term clinical and functional outcomes
after Ross procedure in neonates and infants with and without EFE.

METHODS: Patients who underwent a Ross operation at <1 year of age
between January 2005 and January 2025 were included. Demographic,
echocardiographic, and long-term clinical data were analyzed. Subgroup
assessment was performed in patients with the most pathologic LV, that is,
with EFE, and included cardiac magnetic resonance imaging and
cardiopulmonary exercise testing. The primary outcome was survival;
secondary outcomes included LV function, EFE recurrence, and exercise
capacity.

RESULTS: Thirty-six patients underwent the Ross procedure (median age, 55
days; interquartile range, 20-136), and 17 patients (47%) had EFE.
Operative mortality was 5.6% (2/36), with no late deaths during follow-up
(10 +/- 4 years). Late echocardiography demonstrated unobstructed LV
outflow and normalized LV function at follow-up. Ten patients with EFE,
after we obtained consent for additional diagnostic evaluation, had mostly
normalized LV function confirmed on cardiac magnetic resonance imaging
with no evidence of recurrent EFE. In these 10 patients, cardiopulmonary
exercise testing demonstrated predominantly normal aerobic capacity.

CONCLUSIONS: Biventricular repair in neonates and infants with critical
aortic stenosis is associated with excellent survival and substantial LV
recovery even in the presence of severe EFE.

Baseline peak VO2 and treatment effect consistency of perioperative rehabilitation in cardiac valve surgery: an exploratory subgroup analysis of the PORT trial.

Wang R; chool of Medicine South China University of Technology, Guangzhou, China.
Huang Z; Jiang Z; Bai B;et al

BMC Anesthesiology. 26(1), 2026 Jul 06. VI 1

BACKGROUND: In the PORT trial (Perioperative Rehabilitation in Patients
Undergoing Elective Cardiac Valve Surgery: A Randomised Controlled Trial),
a short-term multidomain perioperative rehabilitation programme was
associated with a reduced incidence of postoperative pneumonia in patients
undergoing elective cardiac valve surgery. Whether baseline peak oxygen
consumption (peak VO2), a marker of cardiorespiratory reserve, modifies
the effect of this intervention remains uncertain.

OBJECTIVES: To evaluate whether the association between perioperative
rehabilitation and postoperative outcomes differs according to baseline
peak VO2 (<= 20 vs. > 20 mL.kg-1.min-1).

METHODS: This exploratory subgroup analysis included 702 participants
from the PORT trial who underwent preoperative cardiopulmonary exercise
testing. Patients were stratified by baseline peak VO2 and randomized to
perioperative rehabilitation-comprising education, inspiratory muscle
training, active cycle of breathing techniques, and early mobilization-or
usual care. The primary endpoint was a composite of in-hospital all-cause
mortality, postoperative pulmonary complications (PPCs), and prolonged
hospitalization (> 7 days). Logistic and Cox regression models adjusted
for prespecified covariates were used to estimate treatment effects within
peak VO2 strata, and treatment-by-peak VO2 interactions were tested.

RESULTS: Of 702 participants, 202 (29%) had peak VO2 >20 and 500 (71%)
had peak VO2 <=20 mL.kg-1.min-1. The composite primary endpoint did not
differ significantly between rehabilitation and usual care in either
stratum (interaction P = 0.62). Perioperative rehabilitation was
associated with a lower incidence of postoperative pneumonia in both peak
VO2 >20 mL.kg-1.min-1 (adjusted OR 0.30; 95% CI 0.13-0.71) and <= 20
mL.kg-1.min-1 (adjusted OR 0.65; 95% CI 0.47-0.90), with no significant
interaction between peak VO2 category and treatment effect (P for
interaction = 0.12). No significant effect modification was observed for
other outcomes, including SICU stay, total hospitalization duration, or
3-month mortality.

CONCLUSIONS: In this exploratory analysis of the PORT trial, the
reduction in postoperative pneumonia associated with short-term
perioperative rehabilitation was consistent across strata of baseline peak
VO2. These findings suggest that the pneumonia benefit of
respiratory-focused perioperative rehabilitation may not depend on
baseline cardiorespiratory fitness, although adequately powered studies
are required to definitively assess effect modification. Although the
observed reduction in pneumonia was statistically significant and
biologically plausible, it arose from a secondary exploratory analysis
without adjustment for multiple comparisons and should therefore be
interpreted with caution.

Inspiratory muscle training as part of multimodal prehabilitation improves maximal inspiratory pressure in elderly surgical patients: an exploratory secondary analysis of a randomised controlled trial. Source

Dueblin SW; Bern University Hospital, University of Bern,Switzerland
Wuethrich PY; Engel D; Eser P; et al

BMC Geriatrics. 26(1), 2026 Jul 07. VI 1

BACKGROUND: Older adults awaiting major surgery often present with reduced
physical fitness and respiratory muscle weakness, which are associated
with increased postoperative complications. Prehabilitation may improve
functional capacity, but evidence for its effect on inspiratory muscle
strength in high-risk older adults remains limited. The main objective was
to assess the change in maximal inspiratory pressure (MIP) in the
preoperative period in high-risk patients receiving home-based
tele-supervised prehabilitation compared to standard care.

METHODS: This exploratory analysis included a subset of secondary outcome
data from a prospective, two-arm, parallel-group randomised controlled
trial conducted at a single university hospital in Switzerland. Patients
aged >= 65 years awaiting elective cardiac or major non-cardiac surgery
with a proven fitness deficit measured by cardiopulmonary exercise testing
(CPET) were included. Participants randomized in the intervention arm
received a multimodal, home-based tele-supervised prehabilitation
programme over 2-4 weeks addressing deficits in physical fitness,
nutrition, and anaemia, while controls received standard preoperative
care.

RESULTS: Eighty eight participants were analysed (intervention n = 48;
control n = 40). Patients in the intervention group showed improvement in
MIP after the training period, whereas the control group demonstrated a
decline (median change + 10.5 [0.00; 16.2] vs. – 3.00 [-8.00; 1.50] cmH2O;

CONCLUSIONS: Home-based tele-supervised IMT, delivered as part of a
multimodal prehabilitation programme, improved maximal inspiratory
pressure over the preoperative period in elderly high-risk surgical
patients. The observed MIP decline in the control group suggests that the
preoperative waiting period itself may carry a risk of functional
deterioration in this population. Whether MIP improvements translate into
reduced postoperative morbidity will be addressed by the primary outcome
of the ongoing PREHABIL trial.

Persistent endothelial dysfunction is associated with exercise intolerance in adults despite preserved myocardial work 3 years after SARS-CoV-2 infection.

de Araujo Alves CC; Laboratory of Clinical Exercise Physiology, Brazil
Goulart CDL; D’Avila L; de Souza Silva et al

Physiological Reports. 14(19):e71103, 2026 Oct. VI 1

Long COVID is frequently associated with persistent exercise intolerance,
although the relative contributions of peripheral vascular dysfunction and
myocardial function remain unclear. We investigated whether persistent
endothelial dysfunction and altered myocardial work (MW) contribute to
exercise intolerance approximately 3 years after SARS-CoV-2 infection.
This case-control study included adults with Long COVID (n = 10) and
controls (n = 11) who underwent cardiopulmonary exercise testing (CPET),
transthoracic echocardiography with global longitudinal strain (GLS) and
MW analysis, and brachial artery flow-mediated dilation (FMD) with
hyperemic shear assessment. Compared with controls, Long COVID
participants exhibited lower peak VO2 (19.6 +/- 2.5 vs. 24.3 +/- 6.5
mL.kg-1.min-1, p = 0.04), percent-predicted peak VO2 (61.1 +/- 8.3 vs.
77.0 +/- 14.2%, p = 0.006), and VO2 at first ventilatory threshold (11.0
+/- 1.4 vs. 13.7 +/- 3.8 mL.kg-1.min-1, p = 0.04). Conventional
echocardiographic parameters and MW indices did not differ between groups
(all p > 0.05). In contrast, endothelial function was impaired in the Long
COVID group, with lower FMD (p < 0.001), peak shear rate (p = 0.01), AUCSR
(p = 0.04), and AUCmax (p = 0.001). FMD correlated positively with
exercise capacity in the Long COVID group (peak VO2: r = 0.68, p =
0.03;percent-predicted peak VO2: r = 0.64, p = 0.04). In conclusion, 3
years after infection, Long COVID remains characterized by endothelial
dysfunction and blunted hyperemic shear despite preserved MW, supporting a
predominantly peripheral vascular basis for persistent exercise
intolerance.

Impact of conotruncal anomalies on outcomes following total cavopulmonary connection.

Avgeridou S ; Department of Congenital and Pediatric Heart Surgery, Munich, Germany.
Matsubara M; Dumitru R; Schaeffer T et al

Cardiol Young. 2026 Jul;36(7):1479-1486.

OBJECTIVES: The impact of conotruncal anomalies on long-term outcomes after total cavopulmonary connection remains unclear, particularly regarding haemodynamic performance and dominant ventricular morphology.
METHODS: All patients who underwent total cavopulmonary connection between 1994 and 2023 at a single centre were reviewed. Conotruncal anomalies were defined as transposition of the great arteries, double outlet right ventricle, tetralogy of Fallot, truncus arteriosus, and interrupted aortic arch type B. Four endpoints were analysed: transplant-free survival, Fontan failure, tachyarrhythmia, and ventricular dysfunction. Multivariable Cox regression, inverse probability of treatment weighting, and subgroup analyses were performed to disentangle conotruncal anomaly effects from dominant ventricular morphology.
RESULTS: Among the 650 patients, 291 (44.8%) were identified with conotruncal anomalies. During a median follow-up of 6.3 years, no differences were observed in transplant-free survival (log-rank p = 0.136) or Fontan failure (p = 0.717) between groups. Dominant right ventricular morphology was independently associated with Fontan failure (hazard ratio: 2.20; p = 0.006) and tachyarrhythmia (hazard ratio: 3.22; p = 0.004). These findings were confirmed across all sensitivity analyses. No differences were detected in filling pressures, cardiac index, or peak oxygen uptake on post-operative catheterisation (n = 226) and cardiopulmonary exercise testing (n = 161). When stratified into four groups by conotruncal status and dominant ventricular morphology, freedom from Fontan failure clustered by morphology rather than diagnostic category (4-way log-rank p < 0.001).
CONCLUSIONS: Conotruncal anomalies are not independently associated with adverse outcomes following total cavopulmonary connection. Dominant right ventricular morphology, not diagnostic category, is the principal determinant of long-term Fontan outcomes

Right ventricular dysfunction in patients with symptomatic atrial fibrillation: Prevalence and functional implications

Dziano, J.K.,Centre for Heart Rhythm Disorders, Royal Adelaide Hospital, Australia
Ariyaratnam, J.P., Howie, J.,et al

Heart Rhythm 2026 10 e2456-e2465

BACKGROUND: Assessment of left ventricular (LV) function is an essential component of guideline-recommended management of atrial fibrillation (AF). However, the role and implications of right ventricular (RV) dysfunction in AF are poorly understood.
OBJECTIVE: This study aimed to determine the prevalence of RV dysfunction and evaluate its association with cardiorespiratory fitness (CRF) and symptom burden in patients with symptomatic AF.
METHODS: Consecutive adults with symptomatic paroxysmal or persistent AF and preserved LV ejection fraction scheduled for catheter ablation underwent transthoracic echocardiography, cardiopulmonary exercise testing, and AF symptom assessment. RV dysfunction was defined as tricuspid annular plane systolic excursion of </=1.7 cm and/or tissue Doppler s’ velocity of </=9.5 cm/s. CRF was determined by peak oxygen consumption (peak oxygen uptake [VO(2peak)]) during cardiopulmonary exercise testing.
RESULTS: Among 241 patients (mean age 66 +/- 10 years; 25% female), RV dysfunction was present in 35 patients (14.5%) despite preserved LV systolic function. Patients with RV dysfunction had lower CRF (VO(2peak) 17.9 +/- 6.7 vs 21.1 +/- 6.6 mL/kg/min; P = .01) independent of rhythm, with a greater proportion exhibiting severely reduced CRF (VO(2peak) <16 mL/kg/min: 43% vs 23%; P = .026). There was no association between RV dysfunction and AF symptom severity (P = .59). Structural chamber dimensions were comparable. Patients with RV dysfunction demonstrated higher E/e’ (P = .006), lower left atrial reservoir strain (P < .001), and LV global longitudinal strain (P < .001).
CONCLUSION: RV dysfunction is present in a substantial proportion of patients with symptomatic AF despite preserved LV systolic function and is independently associated with reduced CRF. Reduced RV function may be considered as a therapeutic target in the treatment of symptomatic AF.

Determinants of cardiorespiratory fitness after successfully reperfused ST-elevation myocardial infarction

Hogwood, A.C. Cardiovascular Research Center Virginia, United States.
Smarz, K., Golino, M., Tysarowski, M et al

Curr Probl Cardiol 2026 10 103382

BACKGROUND: Modern treatment of ST-elevation myocardial infarction (STEMI), emphasizing prompt reperfusion, has improved clinical outcomes by preserving cardiac function. Despite this, cardiorespiratory fitness remains impaired. The purpose of this study was to assess determinants of cardiorespiratory fitness in patients with reperfused STEMI and preserved cardiac function.
METHODS: We prospectively collected data from two patient cohorts with reperfused STEMI who underwent cardiopulmonary exercise testing on either a semi-supine cycle ergometer (Cohort 1) or treadmill (Cohort 2). Peak oxygen consumption (VO(2)) was measured as mL.kg(-1).min(-1) and as percent-predicted. Cardiac reserve was measured with Doppler echocardiography using heart rate (HR), stroke volume (SV), and cardiac output (CO) before and at peak exercise. Arterial-venous oxygen difference (a-v O(2)diff) was calculated using the Fick equation.
RESULTS: We included ninety-five patients (58 [51-65] years, 34% female) tested 41 [37-45] days after STEMI (Cohort 1: n = 39; Cohort 2: n = 56). Resting LVEF was 55 [50-59] %, with 2 (2%) having <40%. E’ velocity was 8.8 [7.3-10.5] and E/e’ was 7.6 [6.5-9.2]. Peak VO(2) was 20.0 [16.3-22.9] mL.kg(-1).min(-1), and 74 (78%) and 24 (25%) patients had reduced peak VO(2) at <80% and <60% of predicted, respectively. A significant positive correlation was observed between peak VO(2) and peak CO (R = 0.42, p = 0.0001), SV (R = 0.24, p = 0.02), HR (R = 0.36, p = 0.006), and a-v O(2)diff (R = 0.49, p < 0.0001). Peak HR and SV were each independent predictors of peak VO(2) using multivariate analyses (all p < 0.01).
CONCLUSION: Cardiorespiratory fitness remains impaired after successfully reperfused recent STEMI, despite rather preserved resting cardiac function. Cardiac and peripheral reserve partially explain the impairments, and preserving these may improve fitness after STEMI.

Physical activity and cardiorespiratory fitness in atherosclerotic cardiovascular disease risk prediction: integrating digital phenotyping, mechanistic insights, and multimodal clinical prediction for actionable stratification

Liu, R., Beijing,  China.
Arena, R., Santos-de-Araujo, A.D., Borghi-Silva, A. & Popovic, D.

Curr Probl Cardiol 2026 10 103399

BACKGROUND: Atherosclerotic cardiovascular disease remains a leading cause of morbidity and mortality worldwide. Established risk equations guide prevention but rely mainly on static, clinic-based variables and incompletely capture physical activity, sedentary behavior, and cardiorespiratory fitness. METHODS: This narrative review synthesizes evidence from epidemiological studies, clinical trials, and methodological frameworks on the roles of physical activity, sedentary behavior, and cardiorespiratory fitness in cardiovascular risk prediction, with emphasis on digital phenotyping, mechanistic exercise physiology, and multimodal clinical prediction models.
RESULTS: Cardiorespiratory fitness reflects integrated physiological reserve and is strongly associated with cardiovascular and all-cause outcomes. Cardiopulmonary exercise testing extends fitness assessment by identifying mechanisms of exercise limitation, including cardiac, ventilatory, autonomic, pulmonary vascular, and peripheral contributors. Wearable technologies provide longitudinal, real-world measures of physical activity and sedentary behavior that complement static clinical risk factors. Multimodal models integrating electronic health records, electrocardiography, imaging, wearable signals, and exercise testing may support more personalized and actionable risk stratification. However, the current evidence base remains limited by insufficient external and prospective validation, incomplete calibration reporting, limited decision-analytic evaluation, and inadequate assessment of subgroup performance and equity.
CONCLUSIONS: Physical activity and cardiorespiratory fitness should be considered clinically relevant and modifiable phenotypes in contemporary cardiovascular risk prediction. Future models should prioritize standardized measurement, mechanistic validation of digital phenotypes, calibration, external validation, subgroup evaluation, workflow feasibility, and prospective evidence of clinical utility before widespread implementation.