Wojciech Kosmala

Objectives: Exercise blood pressure response (EBPR) is influenced by arterial stiffness, reflected by pulse wave velocity (PWV). Adjustment for cardiorespiratory fitness may refine its interpretation. Brachial waveform-derived PWV remains underused due to concerns about age and SBP dependence, and single-point office PWV may inadequately represent the dynamic vascular load driving EBPR. We hypothesized that 24-h PWV would outperform office PWV in predicting EBPR, and that indexing exercise SBP to aerobic fitness would strengthen these associations. Methods: We studied 228 adults (46% men; age 53 ± 12 years) with adequately controlled blood pressure, irrespective of hypertension diagnosis. Individuals with coronary artery disease, valvular disease, or heart failure were excluded. All participants underwent office and 24-h blood pressure monitoring with integrated pulse wave analysis (Mobil-O-Graph), cardiopulmonary exercise testing, and echocardiography. Exercise SBP at submaximal and peak workloads was normalized to peak oxygen uptake (VO ₂ ). Results: Fitness-corrected SBP showed stronger associations with PWV than uncorrected values ( r = 0.64 vs. 0.15; P < 0.001). Both submaximal and peak SBP indexed to peak VO ₂ increased stepwise across 24-h PWV tertiles; this gradient was attenuated without fitness correction. After adjustment for age, sex, SBP, BMI, and left ventricular hypertrophy and diastolic dysfunction, 24-h PWV remained an independent predictor of fitness-corrected EBPR, whereas office PWV was not statistically significant. Conclusion: Brachial BP-waveform-derived PWV independently predicts EBPR. Ambulatory 24-h PWV demonstrates stronger associations with exercise BP behaviour compared with single-time-point office PWV, and fitness-corrected SBP outperforms conventional uncorrected measures.

BACKGROUND: Guidelines advocate the use of dobutamine stress echocardiography (DSE) in low-gradient aortic stenosis (aortic valve area [AVA] 2 with aortic valve mean gradient 2 and aortic valve mean gradient ≥40 mm Hg, moderate AS when AVA ≥1 cm ² , and indeterminate AS when AVA 2 and aortic valve mean gradient 2 at a flow rate ≥210 mL/s or projected AVA 2 ) were assessed. RESULTS: After DSE, 84 (29%) patients had severe AS, 81 (28%) had moderate AS, and 122 (43%) had indeterminate AS. Over the median follow-up of 12.0 (interquartile range, 5–33) months, more patients with severe AS (73%) underwent aortic valve intervention compared with those with moderate (40%) and indeterminate AS (44%; P P =0.03), whereas the benefit was uncertain in the remaining indeterminate AS group (HR, 0.77 [95% CI, 0.22–2.75]; P =0.69). After aortic valve intervention, patients with conventionally diagnosed severe AS had a better outcome compared with patients with reclassified severe AS (HR, 2.88 [95% CI, 1.34–6.21]; P =0.007). CONCLUSIONS: In this real-world study, the transvalvular flow–based criteria for severe AS markedly reduced the number of indeterminate DSE. Within the indeterminate AS group, patients with reclassified severe AS derived benefit from aortic valve intervention.

Aims: To characterize sex-specific patterns of bicuspid aortic valve (BAV) valvulo-aortopathy using consensus phenotyping and to assess how aortic normalization strategies influence sex-related differences in aortic dimensions. Methods and results: We analysed 808 adults with BAV (mean age 49.9 ± 17.5 years; 588 men) from the RE-BAV registry. Valve morphology, aortopathy phenotypes, and clinical valvulo-aortopathy categories were classified according to consensus definitions. Typical and uncomplicated forms were additionally analysed together as a non-complex category. Proximal aortic dimensions were defined as the aortic root and ascending aorta. Valve morphology distribution did not differ by sex. Although the prevalence of aortic dilatation was similar, phenotype distribution differed: women more frequently exhibited the extended phenotype (34.7% vs. 23.3%, P = 0.001), whereas the root phenotype was more common in men (15.1% vs. 7.8%, P = 0.006). Moderate-to-severe aortic regurgitation was more prevalent in men (50.3% vs. 29.1%, P < 0.001). Sex differences in proximal aortic dimensions varied by normalization strategy. For the ascending aorta, indexing to body surface area yielded larger values in women (21.1 ± 4.0 vs. 20.0 ± 4.0 mm/m², P = 0.001), whereas diameter/height showed no sex-related difference at this level. Conversely, the cross-sectional area-to-height ratio remained higher in men across proximal segments, most prominently at the sinuses of Valsalva (6.9 ± 2.0 vs. 5.6 ± 1.6 cm²/m, P < 0.001). Age was independently associated with larger proximal aortic dimensions across all strategies. Conclusion: Sex-related differences in BAV involved aortopathy phenotype, aortic regurgitation burden, and proximal aortic dimensions. Interpretation of proximal aortic dimensions depended on the normalization strategy used, indicating that indexing methods should not be treated as interchangeable.

Traditional left ventricle ejection fraction (LVEF)-centric approaches often detect cardiac dysfunction late and offer limited insights into myocardial mechanics. Myocardial strain imaging by two-dimensional speckle-tracking echocardiography has emerged as a high-sensitivity alternative for comprehensive evaluation of heart failure (HF). This synthesis evaluates the diagnostic, prognostic, and therapeutic monitoring capabilities of multi-chamber strain imaging across the HF spectrum. Based on current evidence, global longitudinal strain (GLS) provides superior sensitivity over LVEF in detecting subclinical myocardial injury. In preclinical settings (Stage B HF), a GLS <16% is an important diagnostic criterion, reclassifying 13% of asymptomatic patients and predicting a four-fold higher risk of HF hospitalization. In cardio-oncology, a 15% relative decline in GLS successfully identifies subclinical toxicity before LVEF drops. Across HF phenotypes, GLS <16% has been incorporated as a minor diagnostic criterion for heart failure with preserved ejection fraction (HFpEF). GLS is a 1.6-fold better prognostic marker than LVEF (particularly in preclinical stages and HFpEF) and exhibits a more linear relationship with mortality. Furthermore, left atrial reservoir strain (<18%) accurately grades diastolic dysfunction, while right ventricular free-wall longitudinal strain acts as a powerful independent predictor of death. In conclusion, strain imaging has expanded from a specialized technique to a part of contemporary HF evaluation. By capturing myocardial mechanics, it enables early detection, precise phenotyping, robust risk stratification, and timely therapy monitoring.

Atrial cardiomyopathy (AtCM) encompasses all forms of electrical atrial dysfunction in combination with mechanical atrial dysfunction, atrial enlargement, and/or excessive atrial fibrosis. A growing body of evidence suggests that AtCM not only represents a consequence of ventricular and valvular heart disease but also, critically, serves as the substrate driving atrial fibrillation (AF) and independently contributes to thromboembolic risk and heart failure (HF). Recent advances in cardiac imaging, electrocardiography, and electroanatomic mapping have enabled characterization of AtCM and quantification of its severity, defining a continuum from atrial health to overt atrial failure. This framework creates an opportunity for targeted interventions that may reverse AtCM and prevent progression to clinical disease. This scientific statement summarizes contemporary evidence regarding the natural history, determinants, and therapeutic modification of AtCM. We describe how targeted management of relevant lifestyle factors and comorbidities may prevent or attenuate AtCM progression and report the response of AtCM to pharmacological and structural interventions for HF and valve disease. Recognition of the bidirectional relationship between AtCM and AF has provided important insights into arrhythmia-mediated remodelling and generated the strongest evidence to date for reverse atrial remodelling following successful rhythm-control strategies. We also review emerging atrial-directed therapies targeting fibrosis, inflammation, metabolic dysfunction, and infiltrative disease. While AtCM appears to be, at least in part, a modifiable disease process, current evidence remains largely observational or mechanistic. We therefore highlight key evidence gaps and future research priorities to identify potentially reversible disease, develop targeted therapies, and translate state-of-the-art atrial phenotyping into improved patient outcomes.

Atrial cardiomyopathy (AtCM) is increasingly recognized as a distinct pathological entity characterized by structural, functional and electrical abnormalities that may predispose to atrial fibrillation, heart failure and other adverse cardiovascular outcomes. Early identification and longitudinal monitoring of atrial remodelling are therefore crucial to improve risk stratification, guide therapeutic decisions, and assess treatment response. However, clinical evaluation alone is often insufficient to capture the complexity and temporal evolution of atrial disease. Multimodality cardiac imaging plays a central role in the detection, characterization and surveillance of AtCM and atrial failure, the latter representing the advanced stage of this continuum. This scientific statement synthesizes the current evidence supporting the use of imaging techniques for monitoring AtCM across diverse clinical scenarios. The strengths and limitations of echocardiography, cardiac magnetic resonance, cardiac computed tomography and nuclear imaging are discussed with respect to atrial size, function, tissue characterization and substrate assessment, with particular emphasis on advanced imaging markers. Furthermore, pragmatic imaging-based algorithms are proposed for the evaluation and follow-up of AtCM in preclinical and overt heart failure, atrial fibrillation, cardiomyopathies, valvular heart disease, and peri-procedural settings. Knowledge gaps, unmet clinical needs and future research priorities are also highlighted. By integrating available evidence into a structured framework, this document aims to support a more standardized—yet personalized—approach to imaging-guided management of AtCM in clinical practice.

Clinical improvement and survival benefit after transcatheter aortic valve replacement (TAVR) are difficult to predict. Despite the identification of multiple predictors of both endpoints, prognostic algorithms in patients undergoing TAVR are not well defined. Aim: To explore factors determining the lack of significant improvement in exercise capacity after TAVR, and investigate whether the predictive profile for poor functional response to TAVR (PFR) could also predict mortality. Methods and results: We enrolled 220 patients (78.0±6.4 yrs) with severe aortic stenosis who underwent TAVR. Pre- and post-procedural (3 months) data were collected, including clinical information, echocardiography with myocardial work assessment, and 6-minute walk test (6MWT). PFR was defined as an increase in 6MWT distance <40m. Only age and atrial fibrillation were independent predictors of both mortality and PFR. Mortality was associated with lower global work index (HR 0.99; p<0.001) and shorter 6MWT distance (HR 0.99; p=0.008). PFR was associated with higher global wasted work (OR 1.003; p=0.026) and less impaired 6MWT relative to predicted values (OR 0.19; p<0.001 for 6MWT <80% predicted). Unsupervised machine learning-based analysis (Partition Around Medoids algorithm) identified clusters associated with mortality but not with PFR. Conclusions: The predictive profiles for PFR and mortality after TAVR show only limited overlap, indicating that these two outcomes warrant distinct prognostic evaluations. The 6MWT may be useful in predicting the likelihood of both outcomes, with lower absolute values being associated with mortality, while higher percentage predicted values – with limited symptomatic benefit. Myocardial work analysis may further enhance prognostic assessment in this population. Abstract Figure:

Exaggerated systolic blood pressure (SBP) during submaximal exercise is associated with increased cardiovascular (CV) risk. However, findings are mixed and new evidence indicates that cardiorespiratory fitness should be considered for proper clinical interpretation of exercise SBP responses. This study aimed to determine the relationship between exercise SBP during submaximal effort corrected and uncorrected for fitness, as well as at peak effort and abnormalities of cardiac structure and function. Each of 231 participants with controlled BP (with or without previously diagnosed hypertension), no evidence for ischemic or valvular heart disease, or heart failure underwent cardiopulmonary exercise testing and resting and exercise echocardiography. Submaximal exercise SBP (measured at the 2^nd stage of Bruce protocol) and peak exercise SBP was corrected for peak VO₂. Associations with TOD – target organ damage (left ventricular [LV] mass, relative wall thickness, diastolic function, LV exercise reserve) were stronger for fitness-corrected than uncorrected exercise SBP. There was a progressive deterioration of cardiac function and structure parameters across the submaximal exercise SBP/peak VO₂ tertiles. Multivariable models demonstrated that fitness-corrected SBP was more closely associated with LV hypertrophy and diastolic dysfunction than uncorrected SBP, and ROC analysis revealed better performance of fitness-corrected SBP than uncorrected SBP (AUC 0.792 vs. 0.627, and 0.808 vs. 0.662, both p < 0.001, for LV hypertrophy and diastolic dysfunction, respectively). Fitness-corrected SBP responses to submaximal exercise can identify more profound target organ damage with respect to cardiac function and structure even among patients with controlled clinic BP. Exaggerated BP response to exercise must be considered relative to fitness for proper clinical interpretation of BP responses to exercise testing.

Background: Cardiac magnetic resonance (CMR) is widely used to determine the underlying cause of left ventricular (LV) systolic dysfunction. Patients with ischemic disease are less frequently referred for CMR, as the underlying disease is often presumed to explain LV systolic dysfunction. However, various etiologies of myocardial impairment may coexist. Late gadolinium enhancement (LGE) is a technique used for tissue characterization, particularly visualization of myocardial fibrosis. Objectives: The aim of this study was to assess the prevalence of LGE patterns suggesting ischemic or non-ischemic etiology of myocardial damage in patients with LV systolic dysfunction with and without known coronary artery disease (CAD). Methods: 131 patients (76% male, 55 ± 15 years old) with LV ejection fraction (LVEF) ≤ 50% in echocardiography underwent CMR between December 2021 and November 2022. Patients were divided according to the known history of CAD. Regional subendocardial and transmural LGE was interpreted as ischemic etiology, whereas midmyocardial and subepicardial LGE was non-ischemic. Results: The mean LVEF assessed in CMR was 35 ± 10%. A total of 122 patients underwent CMR with LGE sequence. LGE was detected in 62% of patients: 34% had a non-ischemic pattern, 16% ischemic, and 11% mixed. LGE patterns did not differ between patients with and without CAD. In every third patient with CAD and almost every second patient without CAD, no myocardial fibrosis was detected. A completely normal CMR study was found in 6% of patients without CAD and 1% of patients with CAD (all p NS). Conclusions: The LGE patterns suggesting ischemic or non-ischemic myocardial damage are similarly prevalent in patients with and without known CAD. The diagnosis based solely on clinical information may be unreliable, as LV dysfunction might have multifactorial origins. The absence of local myocardial fibrosis is relatively common in patients with LV dysfunction, irrespective of its etiology.