INTRODUCTION:In heart failure (HF) patients, guidelines recommend scores for assessing outcomes and heart transplant (HTX) eligibility. However, scores use remains limited and cut-off values for HTX listing not well established.Among the available tools, MECKI score is easy to calculate and likely offers the best prognostic accuracy. Compare MECKI score-based survival with that of HTX recipients and identify a MECKI threshold above which survival is inferior to that of HTX recipients at 5-year. METHODS:Consecutive ambulatory HF patients enrolled in MECKI score programme between January 2010 and January 2022 were evaluated. Primary endpoint was a composite of cardiovascular death, HTX, or left ventricular assist device implantation. Heart transplant survival data were obtained from the International Society of Heart and Lung Transplantation registry updated through 2023. To identify the MECKI score threshold beyond which prognosis is worse than that of HTX recipients, patients were stratified by deciles of MECKI score. RESULTS:We analysed 3865 HF patients (mean age 62.4 ± 12.6 years). Peak VO₂ was 58.2 ± 18.3% predicted; VE/VCO₂ slope 33.2 ± 8.2, haemoglobin 13.5 ± 1.7 g/dL, Na⁺ 139 ± 3 mmol/L, LVEF 33.7 ± 10.4%, and eGFR 73 ± 26 mL/min/1.73 m². Periodic breathing occurred in 15.8% of patients. At 5 years, mean survival was 83.7%.The average 5-year survival of HTX recipients (71.2%) lies between the eighth and ninth MECKI score deciles suggesting a MECKI score value ≥0.1368 as the proper cut-off for HTX listing. CONCLUSION:MECKI score ≥0.1368 may warrant HTX listing, while lower scores support clinical deferral.

Cardiopulmonary exercise testing (CPET) is the reference method for the objective assessment of exercise capacity because it provides an integrated appraisal of cardiovascular, respiratory and metabolic responses to exertion. However, CPET alone quantifies the magnitude of functional impairment without fully resolving the central and peripheral mechanisms that determine exercise intolerance. The integration of CPET with exercise stress echocardiography and near-infrared spectroscopy (NIRS) has therefore emerged as a clinically relevant multimodal strategy. Stress echocardiography provides real-time information on ventricular reserve, filling pressures, pulmonary pressure response, valvular function, pulmonary congestion and dynamic outflow obstruction, whereas NIRS provides continuous insight into skeletal muscle oxygen delivery, extraction and utilization. This narrative review summarizes the physiological rationale, practical workflow, methodological limitations and clinical applications of combined CPET, stress echocardiography and NIRS across heart failure, pulmonary hypertension, peripheral artery disease, cardiomyopathies and sports cardiology. By linking systemic gas exchange, central hemodynamics and peripheral oxygen handling, this approach may move exercise evaluation from a descriptive measure of performance toward a mechanism-based framework for phenotyping, risk stratification and individualized therapeutic decision-making. Further studies are needed to harmonize protocols, validate reproducible multimodal indices and demonstrate incremental prognostic value over conventional testing.

BACKGROUND:In approximately 5-10% of cases, hypertrophic cardiomyopathy (HCM) presents left ventricular remodeling with hypokinesia and dilatation, defined "end-stage" phase (ES) of the disease, typically associated with development of advanced heart failure (HF). Prescription of conventional medical treatments for HF with a reduced ejection fraction (HFrEF) have never been investigated in ES-HCM. METHODS:ES-HCM patients from 11 Italian referral centres were retrospectively evaluated. We included only patients with a last clinical evaluation after 2019, to ensure all patients were potentially evaluated in the era of the "4 HFrEF pillars" (beta blockers [BB], renin-angiotensin system inhibitors [RASi], mineralocorticoid receptor antagonists [MRA], and sodium-glucose cotransporter-2 inhibitors [SGLT2i]). For all patients we collected clinical information, with a focus on medical therapy at last clinical evaluation. RESULTS:The study population included 274 ES-HCM patients (59% males, mean age 60 ± 15 years). All 4 HFrEF pillars were prescribed in 26%. Specifically, 90% were treated with BB, 75% with RASi, 66% with MRA, 46% with SGLT2i. Few differences emerged when comparing patients taking versus not taking BB or RASi. Patients taking versus not taking MRA and SGLT2i more commonly had atrial fibrillation and showed worse echocardiographic features. SGLT2i use was significantly higher among ES-HCM patients with LVEF <40%. CONCLUSIONS:While BB and RASi are commonly used in ES-HCM, MRA and SGLT2i are prescribed less frequently and in patients with a worse clinical profile. Combination of all classes is not common, suggesting both clinical inertia and limitations inherent to the disease pathophysiology.

BACKGROUND:Hypertrophic cardiomyopathy (HCM) is a complex disease in which left ventricular outflow tract (LVOT) obstruction influences both functional capacity and clinical outcomes. However, the clinical relevance of varying obstruction severity remains debated. OBJECTIVES:To evaluate the relationship between LVOT gradient severity and both exercise performance and long-term prognosis in HCM using combined cardiopulmonary exercise testing and stress echocardiography (TTE-CPET). METHODS:We retrospectively analyzed 388 HCM patients undergoing TTE-CPET, stratified into four groups based on peak LVOT gradient: <30 mmHg, 30-49 mmHg, 50-79 mmHg, and ≥80 mmHg. Clinical, echocardiographic, and CPET data were compared. The primary outcome was a composite of NYHA class worsening, heart failure hospitalization, new-onset atrial fibrillation, or progression to end-stage HCM, assessed over a median follow-up of 7.4 years. RESULTS:Only patients with severe obstruction (≥80 mmHg, n=82) showed significantly lower peak VO2 (15.9 vs. 19.7 ml/kg/min, p=0.003), higher pulmonary pressures, more advanced diastolic dysfunction, and greater symptom burden. They also had a higher incidence of adverse events (50.0% vs. 31.6%, p=0.011) and worse event-free survival (log-rank p=0.011). A peak gradient ≥80 mmHg independently predicted adverse outcomes (HR: 1.87; p=0.009), even after adjustment. Patients with intermediate gradients (30-79 mmHg) had generally preserved outcomes, though some exhibited early structural or functional changes. CONCLUSIONS:Severe dynamic LVOT obstruction identifies a high-risk HCM subgroup with impaired exercise capacity and poor prognosis. Intermediate gradients may still warrant close monitoring. TTE-CPET offers critical insight for risk stratification and early intervention.

BACKGROUND:Current guidelines recommend evaluating patients with ambulatory heart failure (HF) for heart transplantation if their peak oxygen consumption (peak VO2) is <12 mL/kg/min. However, these recommendations are based on decades-old data. METHODS:We retrospectively analysed 8060 patients with ambulatory HF with cardiopulmonary exercise testing (CPET) data. The primary analysis focused on 1218 patients with left ventricular ejection fraction <40% and peak VO2 <12 mL/kg/min, enrolled between 2010 and 2022. Survival outcomes (composite of death/left ventricular assist device/heart transplantation) were compared with those of heart transplantation recipients from the International Society for Heart and Lung Transplantation registry. Patients were stratified by ventilatory efficiency (ventilation versus CO2 production slope (VE/VCO2) >34 vs ≤34) and presence of exercise oscillatory ventilation. Survival analyses were performed using Kaplan-Meier curves compared with log-rank tests and Cox proportional hazards models, with heart transplantation survival curves reconstructed from aggregate data. RESULTS:Patients with peak VO2 <12 mL/kg/min demonstrated better survival than heart transplantation recipients, with survival curves intersecting at approximately 2.7 years. Among those with VE/VCO2 ≤34, 10-year mortality risk was halved (p<0.01), with survival curves crossing those of heart transplantation recipients around year 4. Absence of exercise oscillatory ventilation was similarly associated with a 50% lower long-term mortality. Combining VE/VCO2 and exercise oscillatory ventilation identified four distinct risk groups with significantly different 10-year outcomes (p<0.01). Patients with peak VO2 <12 mL/kg/min, VE/VCO2 ≤34 and no exercise oscillatory ventilation exhibited survival comparable to heart transplantation recipients at year 5. CONCLUSIONS:In contemporary practice, a peak VO2 <12 mL/kg/min alone may not reliably identify patients with HF with sufficiently high short-term mortality to warrant heart transplantation referral. VE/VCO2 and exercise oscillatory ventilation provide important additional risk stratification, supporting re-evaluation of transplant referral criteria to reflect improved HF management and outcomes.

Introduction: Hypertrophic cardiomyopathy (HCM) is a genetically mediated myocardial disorder with variable clinical expression and reduced functional capacity. Cardiopulmonary exercise testing when integrated with stress echocardiography (CPET-TTE), offers a comprehensive evaluation of cardiovascular performance. In this study, we aimed to assess the added value of CPET-TTE for risk stratification in HCM using a machine learning–based approach to identify individuals at higher risk for major adverse events Methods: We retrospectively analyzed 413 HCM patients (46% obstructive; 63.1% male; mean age 48.3 years) who underwent CPET with rest and stress echocardiography, 24-hour ECG Holter, cardiac MRI, and genetic testing. Several machine learning models were developed to predict a composite outcome (SCD, aborted SCD, heart transplantation, stroke, myocardial infarction), with Gradient Boosting using Cox proportional hazards loss achieving the best performance. A semi-supervised clustering approach applying k-means to out-of-fold risk scores was used to stratify patients into high- and low-risk groups. Feature importance was assessed using the Kruskal-Wallis test and ranked by -log10(p-value); effect sizes were quantified using eta-squared. Results: Gradient Boosting achieved the best predictive performance (C-index: 0.722). Survival analysis showed a clear separation between high-risk (n = 56, 30.4% events) and low-risk (n = 357, 10.1% events) groups (p < 0.000001). High-risk patients were older (56.0 vs 49.0 years) and had significantly reduced exercise capacity (VO2max%: 49.8% vs 68.0%; AT%: 41.3% vs 55.5%; pVO2: 15.1 vs 19.7 ml/kg/min), greater ventilatory inefficiency (VE/VCO2: 29.0 vs 26.5), lower watt ( 80.0 vs 100.0 W), and oxygen pulse (HR/VO2: 9.7 vs 11.4).No significant differences were observed in rest or peak LVOT gradient (14.5 vs 11.0 mmHg; 31.0 vs 30.0 mmHg) or E/e′ ratio at rest (11.7 vs 11.2) and stress (11.4 vs 10.3). Key features contributing to risk prediction included VO2max%, AT%, pVO2 and VE/VCO2 slope (all p < 0.001). Conclusion: The integration of CPET-TTE parameters with advanced machine learning techniques allowed for effective and clinically relevant risk stratification in patients with hypertrophic cardiomyopathy.. These findings highlight the central prognostic value of exercise capacity and ventilatory efficiency in HCM, supporting the routine use of CPET-TTE as a non-invasive, functional tool for personalized risk assessment.

We chronicle the diagnostic journey of a young patient suffering from severe arrhythmias and left ventricular hypertrophy, for which, after about 15 years of inconclusive genetic testing, a definitive diagnosis was made possible by finding an undescribed homozygous variant in POPDC2, a gene recently associated with CCDs and HCM.

Hypertrophic cardiomyopathy (HCM) is a non-rare genetic cardiomyopathy, with an estimated prevalence of 1:500, characterized by an increase in the left ventricular wall thickness in the absence of increased loading conditions. The hypertrophy is mostly asymmetric and predominantly affects the basal septum and anterior wall. Left ventricular outflow tract obstruction, at rest or after provocative tests, is detected in many patients and represents the primary cause of reduced functional capacity, as well as an independent predictor of sudden cardiac death and advanced heart failure. Until ∼1 year ago, symptomatic patients despite maximal therapy with β-blockers or calcium channel blockers plus disopyramide had only basal septal reduction therapy through myectomy or septal alcoholization as additional therapeutic options. Today, a new class of drugs that inhibit cardiac myosin activity is available for patients with obstructive HCM. In light of the new treatment perspectives, the correct clinical-therapeutic classification of affected patients becomes of fundamental importance for the cardiologist. The aim of this position paper is to increase the knowledge of cardiologists in the field of HCM, defining its epidemiological, genetic, and pathological characteristics, identifying the diagnostic criteria and instrumental methods capable of stratifying the risk profile, with the aim of an optimal therapy tailored on the single patient.

Background: Anderson–Fabry disease (AFD) is a progressive lysosomal storage disorder characterized by systemic glycosphingolipid accumulation. While cardiac imaging plays a central role in disease monitoring, the relationship between structural myocardial changes and exercise capacity remains incompletely defined. This study aimed to evaluate functional impairment in AFD patients using cardiopulmonary exercise testing (CPET) and to determine whether limitations are primarily cardiac or extracardiac in origin. Methods: Thirty-one patients with genetically confirmed AFD were retrospectively enrolled from two tertiary centers. All underwent baseline clinical assessment, resting transthoracic echocardiography (TTE), spirometry, and symptom-limited CPET using a cycle ergometer and a 10 W/min ramp protocol. Echocardiographic parameters included the LVEF, global longitudinal strain (GLS), E/e′ ratio, TAPSE, and PASP. CPET measurements included the peak VO2, anaerobic threshold (AT), VE/VCO2 slope, oxygen pulse (VO2/HR), and VO2/watt ratio. Results: The mean age was 48.4 ± 17.6 years, with most patients classified as NYHA I. LVEF was preserved (62.3 ± 8.6%), and diastolic indices were within normal limits (E/e′ 7.1 ± 2.4), but GLS was impaired (11.3 ± 10.5%). CPET showed reduced peak VO2 (18.6 ± 6.1 mL/kg/min; 71.4% predicted) and early AT (40.8%), with preserved ventilatory efficiency and oxygen pulse. VO2/watt was mildly reduced, suggesting peripheral limitations despite intact central hemodynamics. Conclusions: Functional impairment is common in AFD patients, even with mild cardiac involvement. CPET reveals early systemic limitations not captured by standard imaging, supporting its role in phenotypic characterization and therapeutic decision-making.

Hypertrophic cardiomyopathy (HCM) is a genetically driven myocardial disorder characterized by significant variability in clinical presentation and functional capacity (measured by peak oxygen consumption, pVO2). This study investigates the relationship between functional capacity and adverse events, focusing on rehospitalizations and progression to end–stage HCM. 413 HCM patients (46% obstructive; 63% male;mean age 48 years) were evaluated with CPET combined with concomitant transthoracic stress echocardiography at the cardiomyopathy unit of San Camillo Forlanini Hospital (Rome) Clinical outcomes included sudden cardiac death (SCD), progression to end–stage HCM, rehospitalization, myectomy, and implantable cardioverter–defibrillator (ICD) implantation. The mean pVO² for the cohort was 19.5 ml/kg/min, with 16% of patients demonstrating values below 50% of predicted levels. The mean pVO²% was 68%, and the mean VE/VCO2 slope was 27. Echocardiographic findings showed an average ejection fraction (EF) of 66%, maximal left ventricular wall thickness of 20.5 mm, and peak LVOT gradients of 46 mmHg. Pulmonary artery systolic pressure was 20 mmHg at rest, rising to 36 mmHg during exercise. Mean filling pressure was higher than normal range (mean E/e’septal13.6; lateral: 9.2). During a mean follow–up of 8.7 years, 2.4% of patients progressed to end–stage HCM, and 8.2% underwent invasive interventions (e.g. myectomy or alcohol septal ablation). Device–based therapies (e.g. ICDs) were utilized in 8.2%, and aborted sudden cardiac death was reported in 0.7%. Disease progression to advanced NYHA classes occurred in 18.5% of patients, while rehospitalization in 10.7%. Rehospitalized patients exhibited significantly lower pVO² values (16.7 vs 19.9 ml/kg/min, pVO²% 62 vs 68%, p ‹ 0.05) (Figure 1), higher VE/VCO2 slopes (29 vs 27, p ‹ 0.05), higher filling pressures (E/e’ 17.5 vs 13.2 p ‹ 0.05), compared to those without rehospitalizations. Similarly, patients progressing to end–stage HCM (11.1%) showed reduced functional capacity (pVO² 17.0 vs 19.9 ml/kg/min, pVO²% 58.8 vs 78%, p‹0.05) (Figure 2), higher filling pressures (E/e’ 17 vs 13, p ‹ 0.05), compared to the others. This study highlights the pivotal role of reduced functional capacity in predicting adverse outcomes in HCM. Patients with lower pVO2 are at significantly higher risk of rehospitalizations and progression to end–stage disease, spotting the light on this important clinical information.Figure 1 Figure 2

INTRODUCTION:Approximately two-thirds of patients suffering from hypertrophic cardiomyopathy present with an obstructive (HOCM) physiology. For years, medical therapy has been limited to beta blockers, verapamil and/or disopyramide. Recently, a novel class of drugs, the allosteric inhibitors of the cardiac-specific myosin head adenosine triphosphatase (ATPase), have been demonstrated to be effective in relieving the dynamic obstruction and related clinical condition. In July 2024 the Cardiomyopathies and Pericardial Diseases WG of the Italian Society of Cardiology started with a nationwide multicentre registry aimed at investigating the pathophysiology of dynamic obstruction in real-world patients with HOCM. Based on the medical records, this brief report deals with the proportion of patients who were eligible for Mavacamten based on the Explorer-HCM entry criteria, and then admitted for compassionate use by the end of 2024. METHODS AND RESULTS:The Hypertrophic Obstructive Physiology Study (HOPS) was designed as a registry on consecutive adult patients admitted to 19 tertiary Cardiac Centres in Italy until June 2024. A total of 424 patients, 53% males, aged 64 ± 13 years, were included. We retrospectively recognized 200 Mavacamten-eligible patients (47.2%) on 5 Explorer-HCM requirements. Forty out of this latter group, along with 15 more patients on 4 criteria, were admitted to the compassionate use programme ( n  = 55, 13% of the whole population). Forty-three showed subaortic obstruction and 12 a mid-ventricular variant. Ethical committee approval items varied among centres and regions. DISCUSSION:This study confirmed our recent demonstration that approximately half of real-world HOCM patients are suitable for Mavacamten therapy based on the full Explorer-HCM trial entry criteria. Due to the current limitation of compassionate use programmes in Italy, only one in four patients was admitted for treatment.

A 46–year–old male with hypertrophic obstructive cardiomyopathy (HOCM) due to a MYH7 mutation was diagnosed at age 30 through familial screening. Despite treatment with bisoprolol and disopyramide at maximum tolerated doses, the patient experienced persistent dyspnea with mild exertion. Investigations revealed characteristic ECG findings: pseudonecrosis Q waves in V1–V2, ST–segment elevation in the same leads, fragmented QRS complexes, and signs of left ventricular (LV) hypertrophy and overload (Figure 1 lower part). An echocardiogram in April 2024 showed normal ejection fraction, a septal maximum wall thickness (MWT) of 19 mm, LV outflow tract (LVOT) obstruction (gradient of 35 mmHg, increasing to 52 mmHg with Valsalva), elevated filling pressures (E/e′ = 13), and left atrial (LA) enlargement (LAVi = 50 ml/m²) (Figure 2 lower part). CPET and stress echocardiography confirmed an increased LVOT gradient (75 mmHg), worsening diastolic function, reduced exercise capacity (VO2 = 15.1 ml/min/kg, 67% predicted), and reduced ventilatory efficiency (VE/VCO2s = 32.3) (Figure 3 left part). In April 2024, the patient initiated therapy with Mavacamten (cardiac myosin inhibitor), up to 10 mg/day, and discontinued disopyramide within a month. Subjective improvement was reported within 20 days, including resolution of dyspnea. Follow–up evaluations demonstrated progressive normalization of ECG findings within two months, including reduced QRS fragmentation and near–complete resolution of repolarization abnormalities (Figure 1 upper part). After 30 weeks of Mavacamten therapy, echocardiography revealed reduced septal wall thickness (MWT = 15 mm), resolution of LVOT obstruction, improved diastolic function (E/e′ = 9), and decreased LA volume (LAVi = 37 ml/m²) (Figure 2 upper part). CPET showed no LVOT gradient, improved exercise capacity (VO2 = 21 ml/min/kg, 91% predicted), and enhanced ventilatory efficiency (VE/VCO2s = 27.5) (Figure 3 right part). This case illustrates the efficacy of Mavacamten in treating HOCM, demonstrating its impact on both structural remodeling (e.g., reduced wall thickness and atrial size) and functional improvement (e.g., resolution of obstruction, enhanced exercise capacity). Mavacamten’s therapeutic potential extends to delaying or avoiding surgical interventions, including myectomy, by addressing underlying pathophysiology. Mavacamten is a promising treatment for HOCM, offering substantial benefits in structural, functional, and symptomatic domains, as demonstrated by this patient’s remarkable clinical and echocardiographic recovery.Figure 1 Figure 2 Figure 3

La cardiomiopatia ipertrofica è una cardiomiopatia genetica non rara, con una prevalenza stimata di 1:500, caratterizzata da un aumento dello spessore delle pareti del ventricolo sinistro, in assenza di aumentate condizioni di carico. L’ipertrofia è per lo più asimmetrica e interessa prevalentemente il setto basale e la parete anteriore. L’ostruzione al tratto di efflusso del ventricolo sinistro (LVOTO), a riposo o dopo manovre provocative, si riscontra in un elevato numero di pazienti e rappresenta la causa primaria di ridotta capacità funzionale, oltre ad essere un predittore indipendente di morte cardiaca improvvisa e insufficienza cardiaca avanzata. Fino a circa 1 anno fa i pazienti con LVOTO, sintomatici nonostante terapia massimale con beta-bloccanti o calcio-antagonisti, con o senza disopiramide, potevano essere trattati solo con terapia di riduzione del setto basale tramite miectomia o alcolizzazione settale. Attualmente, una nuova classe di farmaci inibitori della miosina cardiaca si è resa disponibile per questa categoria di pazienti.Alla luce delle nuove prospettive di trattamento, diventa di fondamentale importanza per il cardiologo il corretto inquadramento clinico-terapeutico dei pazienti affetti. Scopo di questo position paper è quello di aumentare le conoscenze dei cardiologi nell’ambito della cardiomiopatia ipertrofica, definendone le caratteristiche epidemiologiche, genetiche e patologiche, identificandone i criteri diagnostici e le metodiche strumentali in grado di stratificare il profilo di rischio, allo scopo di ottimizzare la terapia nel singolo paziente.

AIMS:Electrocardiogram (ECG) analysis plays a central role in Anderson-Fabry disease (AFD) diagnosis and management. This study aimed to assess ECG evolution during follow-up in relation to specific treatment and disease progression. METHODS:Retrospective study of a multicentric cohort of AFD patients with ≥2 ECG and echocardiographic data. Specific treatment status (enzyme replacement or chaperone) was defined as: chronic therapy (≥ 1 year before the first ECG); therapy started during the follow-up; no therapy. RESULTS:One-hundred-eighty-one AFD patients (median age 46 years, IQR 35-58; 36 % male; 67 % classic phenotype composed the study population: 24 % were on chronic therapy; 39 % started the therapy during follow-up; 37 % had no specific therapy. During a median follow-up of 62 months (IQR 33-83), significant ECG variations were: atrial fibrillation detection (p = 0.005), PendQ interval (p = 0.04), left atrial enlargement (p < 0.001), new right bundle branch block (RBBB, p < 0.001), QRS interval (p < 0.001), QRS fragmentation (p = 0.024), QTc (p = 0.001), and symmetric lateral negative T waves development (p = 0.016). PendQ interval showed a significant interaction with treatment status, significantly increasing in patients without or on chronic therapy but slightly reducing in patients who started the specific therapy during follow-up (p for interaction = 0.035). PendQ interval, new RBBB and pathologic QTc were associated with left ventricle wall thickness increase (p = 0.003, p = 0.014, p = 0.019, respectively). CONCLUSIONS:In this multicentric cohort of AFD patients, several ECG parameters showed significant changes during follow-up. Only PendQ interval showed a significant interaction with treatment status. Moreover, PendQ interval, new RBBB and pathologic QTc development were associated with cardiac hypertrophy progression.

Abstract Background The left ventricular (LV) hypercontractile phenotype (HP) plays a critical role in hypertrophic cardiomyopathy (HCM) and is usually identified with the left ventricular outflow tract gradient (LVOTG). Purpose To assess the systemic and coronary hemodynamic profile associated with HP identified with increased LV elastance (also known as force) at rest in patients with HCM. Methods We enrolled 1248 HCM patients (age 50 ± 15 years, 798 males, 64%) with ejection fraction (EF) ≥50%, referred for rest transthoracic echocardiography (TTE) in 14 quality-controlled sites from 7 countries TTE assessment included LVOTG, EF, and LV force (systolic blood pressure + LVOTG/LV end-systolic volume, mmHg/mL). Volumetric echocardiography with Simpson’s method was used to measure EF from end-diastolic volume (EDV) and end-systolic volume (ESV), stroke volume (SV), arterial elastance (AE) and ventricular-arterial coupling (VAC). We also assessed resting peak diastolic coronary flow velocity (D-CFV) in the mid-distal left anterior descending artery in a subset of 275 patients. Results EF equaled 68 ± 7%, force = 6.8 ± 5.3 mmHg/ml and LVOTG = 22 ± 28 mmHg. HP was identified as the highest quartile of force (> 7.85 mmHg/ml, mean value= 13.3 ± 7.0). HP showed the lowest SV (46 ± 18 ml) and EDV (61 ± 20 ml), with the highest AE (3.19 ± 1.35 mmHg/ml) and VAC (3.46 ± 1.59) compared to other quartiles (p<0.001) ( see Picture) . D-CFV was not higher in patients with HP (n = 65) compared to those (n = 210) without HP (41± 11 vs 38 ± 14 cm/s, p=ns, but higher in comparison to joint first and second Force quartile (n=122) vs 37 ±14 p =0.0472). Table displays the demografic, clinical and TTE parameters related to HP (Table). In multivariate logistic analysis 4 independent predictors of HP were identified: SBP >130 mmHg with OR 2.5, female sex with OR 5.4, LV EF >70% with OR 6.1 and LVOTG >30 mmHg with the highest OR = 6.3. Conclusion: HCM patients with HP exhibit a distinctive systemic hemodynamic and coronary physiology profile, characterized by low SV, high VAC, and supranormal baseline D-CFV compared to non-HP patients. These findings suggest reduced cardiovascular efficiency and increased myocardial oxygen demand, possibly detrimental over time.

Background: Electrocardiographic findings in arrhythmogenic left ventricular cardiomyopathy (ALVC) have been limited to small studies. Objectives: The authors aimed to analyze the electrocardiogram (ECG) characteristics of ALVC, to correlate ECG with cardiac magnetic resonance and genetic data, and to evaluate its prognostic value. Methods: We reviewed data of 125 consecutive patients with ALVC (81.5% desmoplakin pathogenic/likely pathogenic variants). The composite endpoint of major arrhythmic events (MAEs) included sudden cardiac death, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator shock. Predictors of MAE were evaluated with logistic regression. Results: ALVC showed distinct ECG signs, including left posterior fascicular block (LPFB) (13.6%), pathological Q waves (26.4%), R/S ratio in V1 ≥0.5 (26.4%), and SV1 + RV6 ≤12 mm and RI + RII ≤8 mm (44%). Fifteen (12%) patients had a normal ECG. MAE occurred in 35 patients (28%). In multivariable analysis, LPFB (OR: 4.7; 95% CI: 1.2-18.3), syncope (OR: 84.95; 95% CI: 14-496), transmural late gadolinium enhancement (OR: 9.95; 95% CI: 2.3-36), and right ventricular ejection fraction (OR: 0.92; 95% CI: 0.87-0.97) were the independent predictors of MAE. The model including these 4 variables achieved a remarkable predictive capability (area under the curve: 0.9). In the primary prevention scenario, with Cox regression, LPFB (HR: 3.98; 95% CI: 1.3-12.0), syncope (HR: 19.13; 95% CI: 5.8-63.0), and transmural late gadolinium enhancement (HR: 10.57; 95% CI: 2.9-38.0) were independent predictors of MAE. Conclusions: In ALVC, ECG is a valuable diagnostic tool and may have a relevant prognostic role, since LFPB is a strong and independent predictor of MAE.

Background: Hypertrophic cardiomyopathy (HCM) is a heterogeneous myocardial disease in which conventional prognostic models, primarily focused on sudden cardiac death, often fail to identify patients at risk of clinically relevant events such as heart failure progression or rehospitalization. Cardiopulmonary exercise testing (CPET) quantifies functional capacity, while stress echocardiography (SE) provides mechanistic insights into exercise-induced hemodynamic changes. Their combined application (CPET–SE) may enhance risk stratification in patients with HCM. Methods: In this retrospective study, 388 patients with obstructive and non-obstructive HCM (mean age 48 ± 15 years, 63.1% male) underwent baseline CPET–SE between 2010 and 2022 and were followed for a median of 7.4 years [IQR 4.3–10.2]. Echocardiographic parameters were assessed at rest and peak exercise, and CPET indices included peak oxygen consumption (pVO2), ventilatory efficiency, and anaerobic threshold. The primary outcome was a composite of heart failure hospitalization or progression to end-stage HCM. Results: Over a median follow-up of 7.4 years, 63 patients (16.2%) experienced an event of the primary outcome. Patients who developed a primary outcome had greater left atrial diameter (45.0 vs. 41.0 mm, p < 0.001) and indexed volume at rest (36.4 vs. 29.0 mL/m2, p < 0.001), with further dilation during stress (p = 0.046); increased LV wall thickness (p = 0.001); higher average E/e′ at rest and during stress (p ≤ 0.004); and higher pulmonary artery systolic pressure at rest (p = 0.027) and during stress (p = 0.044). CPET findings included lower pVO2 (16.0 vs. 19.5 mL/kg/min, p = 0.001), reduced % predicted pVO2 (p = 0.006), earlier anaerobic threshold (p = 0.032), impaired ventilatory efficiency (p = 0.048), and chronotropic incompetence (p < 0.001) in patients who experienced a primary outcome. Multivariable analysis identified dyslipidemia (OR 2.58), higher E/e′ (OR 1.06), and lower pVO2 (OR 0.92) as independently associated with the primary outcome. Conclusions: CPET–SE provided a comprehensive evaluation of patients with HCM, associating aerobic capacity to its hemodynamic determinants. Reduced pVO2 showed the strongest association with adverse outcomes, while exercise-induced diastolic dysfunction and elevated pulmonary pressures identified a high-risk phenotype. Incorporating CPET–SE into longitudinal management of patients with HCM may enable earlier detection of physiological decompensation and guide personalized therapeutic strategies.

AIMS:Our aim was to assess the clinical and prognostic significance of the left ventricular (LV) hypercontractile phenotype (HP) in hypertrophic cardiomyopathy (HCM), which until now remains unclear. METHODS AND RESULTS:We enrolled 1533 HCM patients (age 51 ± 15 years, 965 males, 63%) with ejection fraction (EF) ≥ 50%, referred for rest transthoracic echocardiography (TTE) in 27 laboratories from 13 countries. Two-dimensional volumetric TTE assessment included LV outflow tract gradient (LVOTG), LV EF, and LV force (systolic blood pressure + LVOTG/ESV, mmHg/mL). HP was defined as the highest quartile of the force (> 7.32 mmHg/mL). Survival analysis was performed in a subset of 1200 patients with follow-up information. Compared with non-HP patients, HP showed higher heart rate (72 ± 14 vs. 67 ± 14 beats per minute, P < 0.001), lower stroke volume (50 ± 22 vs. 67 ± 22 mL, P < 0.001), larger left atrial volume index (44 ± 16 vs. 40 ± 16 mL/m2, P = 0.011) and higher coronary flow velocity in the mid-distal left anterior descending artery (n = 325, 41 ± 12 vs. 37 ± 14 cm/s, P = 0.021). Force was moderately related to LV EF (r = 0.48, P < 0.001) and weakly to LVOTG (r = 0.36, P < 0.001). During a median follow-up of 87 months (interquartile range 45-143 months), 131 all-cause deaths occurred. At multivariable Cox analysis, a force > 7.32 mmHg (the fourth quartile for analyzed patients) was associated with a hazard ratio of 1.44 (95% Confidence intervals 1.00-2.07) for all-cause death, independently of LVOTG and LV EF. CONCLUSION:HP in HCM is associated with a disadvantageous systemic, cardiac and coronary hemodynamic profile as well as lower survival in the long-term.

Obstructive hypertrophic cardiomyopathy (oHCM) leads to impaired exercise capacity. Septal myectomy improves symptoms and quality of life by reducing left ventricular outflow tract obstruction (LVOTO), though its impact on peak oxygen consumption (pVO2) varies. To evaluate the effects of myectomy on exercise capacity using combined cardiopulmonary exercise testing (CPET) and echocardiography (Echo-CPET) to assess functional and hemodynamic parameters. Nineteen oHCM patients underwent Echo-CPET before and 13.6 months after septal myectomy at San Camillo Forlanini Hospital. Symptom burden was assessed using the NYHA classification and Minnesota Living with Heart Failure Questionnaire (MLHFQ). Standard ECG and transthoracic echocardiography were performed at rest and during CPET to evaluate LVOT gradients and mitral regurgitation. The mean age was 47.5 years, 63% were male. Before surgery, 52% of patients were NYHA class II and 48% were class III. Following surgery, pVO2 increased significantly (16 to 18.6 mL/kg/min, p=0.02), though 26% of patients (non-responders) showed no pVO2 improvement. LVOT gradient decreased significantly at rest (52±33.5 to 10.7±12.5 mmHg, p=0.0001) and during exercise (59.6±43 to 14.4±6.2 mmHg, p=0.002). No significant changes were observed in echocardiographic parameters like ejection fraction and diastolic function. Mitral regurgitation and systolic anterior motion were resolved post-surgery. Quality of life improved, as reflected by a reduction in the MLHFQ score from 30 to 24.2 (p=0.04), alongside a better NYHA classification. Surgical myectomy effectively reduces LVOT obstruction and improves pVO2, NYHA class, and quality of life of oHCM patients. Diastolic dysfunction, among other factors, could explain the failure to increase pVO2 in some patients.