Physical exercise in hypertensive heart disease: From the differential diagnosis to the complementary role of exercise.

Arterial hypertension (AH) is one of the most common pathologic conditions and uncontrolled AH is a leading risk factor for cardiovascular disease and mortality. AH chronically causes myocardial and arterial remodelling with hemodynamic changes affecting the heart and other organs, with potentially irreversible consequences leading to poor outcomes. Therefore, a proper and early treatment of AH is crucial after the diagnosis. Beyond medical treatment, physical exercise also plays a therapeutic role in reducing blood pressure, given its potential effects on sympathetic tone, renin-angiotensin-aldosterone system, and endothelial function. International scientific societies recommend physical exercise among lifestyle modifications to treat AH in the first stages of the disease. Moreover, some studies have also shown its usefulness in addition to drugs to reduce blood pressure further. Therefore, an accurate, personalized exercise prescription is recommended to optimize the prevention and treatment of hypertension. On the other hand, uncontrolled AH in athletes requires proper risk stratification and careful evaluation to practice competitive sports safely. Moreover, the differential diagnosis between hypertensive heart disease and athlete's heart is sometimes challenging and requires a careful and comprehensive interpretation in order not to misinterpret the clinical findings. The present review aims to discuss the relationship between hypertensive heart disease and physical exercise, from diagnostic tools to prevention and treatment strategies.

OPTImal PHARMacological therapy for patients with heart failure: Rationale and design of the OPTIPHARM-HF registry.

AIMS: Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes. METHODS: The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events. CONCLUSION: The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients.

Hypertriglyceridemia: Molecular and Genetic Landscapes.

Lipid disorders represent one of the most worrisome cardiovascular risk factors. The focus on the impact of lipids on cardiac and vascular health usually concerns low-density lipoprotein cholesterol, while the role of triglycerides (TGs) is given poor attention. The literature provides data on the impact of higher plasma concentrations in TGs on the cardiovascular system and, therefore, on the outcomes and comorbidities of patients. The risk for coronary heart diseases varies from 57 to 76% in patients with hypertriglyceridemia. Specifically, the higher the plasma concentrations in TGs, the higher the incidence and prevalence of death, myocardial infarction, and stroke. Nevertheless, the metabolism of TGs and the exact physiopathologic mechanisms which try to explain the relationship between TGs and cardiovascular outcomes are not completely understood. The aims of this narrative review were as follows: to provide a comprehensive evaluation of the metabolism of triglycerides and a possible suggestion for understanding the targets for counteracting hypertriglyceridemia; to describe the inner physiopathological background for the relationship between vascular and cardiac damages derived from higher plasma concentrations in TGs; and to outline the need for promoting further insights in therapies for reducing TGs plasma levels.

Echocardiographic and clinical features of patients developing prosthesis-patient mismatch after TAVR: insights from the Recovery TAVR registry.

BACKGROUND: The impact of prosthesis-patient mismatch (PPM) on major endpoints after transcatheter aortic valve replacement (TAVR) is controversial and the effects on progression of heart damage are poorly investigated. Therefore, our study aims to evaluate the prevalence and predictors of PPM in a "real world" cohort of patients at intermediate and low surgical risk, its impact on mortality and the clinical-echocardiographic progression of heart damage. METHODS: 963 patients who underwent TAVR procedure between 2017 and 2021, from the RECOVERY-TAVR international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data of these patients were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations, using VARC-3 criteria. RESULTS: 18% of patients developed post-TAVR. PPM, and 7.7% of the whole cohort had severe PPM. At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, p=0.33), aged 82 (IQR 79-85y) years vs 82 (IQR 78-86 p=0.46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, p=0.04); they had smaller left ventricular outflow tract (LVOT) diameter (20 mm, IQR 19-21 vs 20 mm, IQR 20-22, p=0.02), reduced SVi (34.2 vs 38 ml/m2, p<0.01) and transaortic flow rate (190.6 vs 211 ml/s, p<0.01). At pre-discharge FU patients with PPM had more paravalvular aortic regurgitation (moderate-severe AR 15.8% vs 9.2%, p<0.01). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in end-systolic diameter (33 mm vs 28 mm, p=0.03) and a significant increase in left ventricle end systolic indexed volume in those with moderate and severe PPM (52 IQR 42-64 and 52, IQR 41-64 vs.44 IQR 35-59 in those without, p=0.02)). No evidence of a significant impact of PPM on overall (p=0.71) and CV (p=0.70) mortality was observed. Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, p=0.03). Prosthesis size≤23 mm (OR 11.6, 1.68-80.1) was an independent predictor of PPM, while SVi (OR 0.87, 0.83-0.91, p<0.001) and LVOT diameter (OR 0.79, 0.65-0.95, p=0.01) had protective effect. CONCLUSIONS: PPM was observed in 18% of patients undergoing TAVR. Echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations, possibly precursor to a reduction in cardiac function, associated with a significant deterioration in NYHA class at 1 year. These findings emphasize the importance of prevention of PPM of any grade in patients undergoing TAVR procedure, especially in populations at risk.

Myocardial Work Indices Predict Hospitalization in Patients with Advanced Heart Failure.

BACKGROUND: An increasing proportion of heart failure (HF) patients progress to the advanced stage (AdHF) with high event rates and limited treatment options. Echocardiography, particularly Speckle Tracking-derived myocardial work (MW), is useful for HF diagnosis and prognosis. We aimed to assess MW's feasibility in the prognostic stratification of AdHF. METHODS: We retrospectively screened patients with AdHF who accessed our hospital in 2018-2022. We excluded subjects with inadequate acoustic windows; unavailable brachial artery cuff pressure at the time of the echocardiography; atrial fibrillation; and mitral or aortic regurgitation. We measured standard parameters and left ventricular (LV) strain (LS) and MW. The population was followed up to determine the composite outcomes of all-cause mortality, left ventricular assist device implantation and heart transplantation (primary endpoint), as well as unplanned HF hospitalization (secondary endpoint). RESULTS: We enrolled 138 patients, prevalently males (79.7%), with a median age of 58 years (IQR 50-62). AdHF etiology was predominantly non-ischemic (65.9%). Thirty-five patients developed a composite event during a median follow-up of 636 days (IQR 323-868). Diastolic function, pulmonary pressures, and LV GLS and LV MW indices were not associated with major events. Contrarily, for the secondary endpoint, the hazard ratio for each increase in global work index (GWI) by 50 mmHg% was 0.90 (p = 0.025) and for each increase in global constructive work (GCW) by 50 mmHg% was 0.90 (p = 0.022). Kaplan-Meier demonstrated better endpoint-free survival, with an LV GWI ≥ 369 mmHg%. CONCLUSIONS: GWI and GCW, with good feasibility, can help in the better characterization of patients with AdHF at higher risk of HF hospitalization and adverse events, identifying the need for closer follow-up or additional HF therapy.

Aortopathy and aortic valve surgery in patients with bicuspid aortic valve with and without raphe.

AIM: To evaluate the association between raphe in bicuspid aortic valve (BAV) patients and valve dysfunction, aortopathy and aortic valve surgery in the REBECCA registry [REgistro della valvola aortica Bicuspide della Società Italiana di ECocardiografia e CArdiovascular Imaging (SIECVI)]. METHODS: Prevalence of aortic valve dysfunction and aortopathy was investigated in BAV patients with and without raphe. Aortic valve dysfunction (regurgitation or stenosis) was categorized as mild, moderate and severe. Aortopathy was defined as annulus ≥14 mm/m2; root ≥20 mm/m2; sinotubular junction ≥16 mm/m2; ascending aorta ≥17 mm/m2, and classified in Type A, isolated ascending aorta dilatation; Type B, aortic root and ascending aorta dilatation; and Type C, isolated aortic root dilatation. RESULTS: Overall, 695 patients with BAV were enrolled; 520 (74.8%) with raphe and 175 (25.2%) without raphe. BAV patients with raphe presented more frequently with moderate or severe aortic stenosis than BAV patients without raphe (183 [35.2%] vs 34 [19.4%], p < 0.001). A higher prevalence of aortopathy, particularly Type B, was observed in patients with vs without raphe. At multivariable analysis, raphe was a predictor of aortic valve surgery at three-year follow-up (odds ratio 2.19, 95% confidence interval 1.08-4.44, p < 0.001). CONCLUSIONS: Patients with BAV and raphe have a higher prevalence of significant aortic stenosis, aortopathy, especially Type B, and a higher risk of undergoing aortic valve surgery at three-year follow-up.

Risk Score for Long-Term Survival and Major Adverse Cardiovascular and Cerebrovascular Events After Coronary Artery Bypass Grafting Surgery.

To develop risk scoring models predicting long-term survival and major adverse cardiovascular and cerebrovascular events (MACCEs), including myocardial infarction and stroke after coronary artery bypass grafting (CABG). All 4,821 consecutive patients who underwent isolated CABG at Lankenau between January 2005 and July 2021 were included. MACCE was defined as all-cause mortality + myocardial infarction + stroke. Variable selection for both outcomes was obtained using a double-selection logit least absolute shrinkage and selection operator with adaptive selection. Model performance was internally evaluated by calibration and accuracy using bootstrap cross-validation. Mortality and MACCEs were compared in patients split into 3 groups based on the predicted risk scores for all-cause mortality and MACCEs. An external validation of our database was performed with 665 patients from the University of Brescia, Italy. Preoperative risk predictors were found to be predictors for all-cause mortality and MACCEs. In addition, being of African-American ethnicity is a significant predictor for MACCEs after isolated CABG. The areas under the curve (AUCs), which measures the discrimination of the models, were 80.4%, 79.1%, 81.3%, and 79.2% for mortality at 1, 2, 3, and 5 years follow-up. The AUCs for MACCEs were 75%, 72.5%, 73.8%, and 72.7% at 1, 2, 3, and 5 years follow-up. For external validation, the AUCs for all-cause mortality and MACCEs at 1, 2, 3, and 5 years were 73.7%, 70.8%, 68.7%, and 72.2% and 72.3%, 68.2%, 65.6%, and 69.6%, respectively. The Advanced (AD) Coronary Risk Score for All-Cause Mortality and MACCE provide good discrimination of long-term mortality and MACCEs after isolated CABG. External validation observed a more AUCs greater than 70%.

New perspectives in the echocardiographic hemodynamics multiparametric assessment of patients with heart failure.

International Guidelines consider left ventricular ejection fraction (LVEF) as an important parameter to categorize patients with heart failure (HF) and to define recommended treatments in clinical practice. However, LVEF has some technical and clinical limitations, being derived from geometric assumptions and is unable to evaluate intrinsic myocardial function and LV filling pressure (LVFP). Moreover, it has been shown to fail to predict clinical outcome in patients with end-stage HF. The analysis of LV antegrade flow derived from pulsed-wave Doppler (stroke volume index, stroke distance, cardiac output, and cardiac index) and non-invasive evaluation of LVFP have demonstrated some advantages and prognostic implications in HF patients. Speckle tracking echocardiography (STE) is able to unmask intrinsic myocardial systolic dysfunction in HF patients, particularly in those with LV preserved EF, hence allowing analysis of LV, right ventricular and left atrial (LA) intrinsic myocardial function (global peak atrial LS, (PALS)). Global PALS has been proven a reliable index of LVFP which could fill the gaps "gray zone" in the previous Guidelines algorithm for the assessment of LV diastolic dysfunction and LVFP, being added to the latest European Association of Cardiovascular Imaging Consensus document for the use of multimodality imaging in evaluating HFpEF. The aim of this review is to highlight the importance of the hemodynamics multiparametric approach of assessing myocardial function (from LVFP to stroke volume) in patients with HF, thus overcoming the limitations of LVEF.

Reverse Septal Movement: A Step Forward in the Comprehension of the Underlying Causes.

(1) Background: Reverse septal movement (RSM) often occurs after cardiac surgery, consisting of a paradoxical systolic movement of the interventricular septum. In this retrospective study, we aimed to investigate possible determinants of RSM after coronary artery bypass surgery (CABG). (2) Methods: Patients who underwent CABG with on- or off-pump techniques at our center from March 2019 to October 2021 were retrospectively included. Exclusion criteria were: exposure to combined procedures (e.g., valve implantation), prior cardiac surgery, intraventricular conduction delays, and previous pacemaker implantation. Laboratory tests and echocardiographic and cardiopulmonary bypass (CPB) duration data were collected. (3) Results: We enrolled 138 patients, of whom 32 (23.2%) underwent off-pump CABG. Approximately 89.1% of the population was male; the mean age was 70 ± 11 years. There was no difference in RSM incidence in patients undergoing the off-pump and on-pump techniques (71.9% vs. 62.3%; p = 0.319). In patients undergoing on-pump surgery, the incidence of RSM was slightly higher in longer CPB procedures (OR 1.02 (1.00-1.03) p = 0.012), and clamping aortic time was also greater (OR 1.02 (1.00-1.03) p = 0.042). (4) Conclusions: CPB length seems to be correlated with a higher RSM appearance. This better knowledge of RSM reinforces the safety of CABG and its neutral effect on global biventricular function.

Role of speckle tracking echocardiography beyond current guidelines in cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is a device-based treatment applied to patients with a specific profile of heart failure. According to current guidelines, indication for CRT is given on the basis of QRS morphology and duration, and traditional transthoracic echocardiography is mainly used to estimate left ventricular (LV) ejection fraction. However, the identification of patients who may benefit from CRT remains challenging, since the application of the above-mentioned guidelines is still associated with a high rate of non-responders. The assessment of various aspects of LV mechanics (including contractile synchrony, coordination and propagation, and myocardial work) performed by conventional and novel ultrasound technologies, first of all speckle tracking echocardiography (STE), may provide additional, useful information for CRT patients' selection, in particular among non-LBBB patients, who generally respond less to CRT. A multiparametric approach, based on the combination of ECG criteria and echocardiographic indices of LV dyssynchrony/discoordination would be desirable to improve the prediction of CRT response.

Right ventricular dysfunction in left ventricular assist device candidates: is it time to change our prospective?

The use of left ventricular assist devices (LVAD) has significantly increased in the last years, trying to offer a therapeutic alternative to heart transplantation, in light also to the significant heart donor shortage compared to the growing advanced heart failure population. Despite technological improvements in the devices, LVAD-related mortality is still fairly high, with right heart failure being one of the predominant predictors. Therefore, many efforts have been made toward a thorough right ventricular (RV) evaluation prior to LVAD implant, considering clinical, laboratory, echocardiographic, and invasive hemodynamic parameters. However, there is high heterogeneity regarding both which predictor is the strongest as well as the relative cut-off values, and a consensus has not been reached yet, increasing the risk of facing patients in which the distinction between good or poor RV function cannot be surely reached. In parallel, due to technological development and availability of mechanical circulatory support of the RV, LVADs are being considered even in patients with suboptimal RV function. The aim of our review is to analyze the current evidence regarding the role of RV function prior to LVAD and its evaluation, pointing out the extreme variability in parameters that are currently assessed and future prospective regarding new diagnostic tools. Finally, we attempt to gather the available information on the therapeutic strategies to use in the peri-operative phase, in order to reduce the incidence of RV failure, especially in patients in which the preoperative evaluation highlighted some conflicting results with regard to ventricular function.

Myocardial work and left heart deformation parameters across primary mitral regurgitation severity.

AIMS: Myocardial work (MW) estimation by pressure-strain loops using speckle tracking echocardiography (STE) has shown to evaluate left ventricular (LV) contraction overcoming the load-dependency limit of LV global longitudinal strain (GLS). This has proved useful in hemodynamic variation settings e.g. heart failure and valvular heart disease. However, the variation of MW and strain parameters across different stages of primary mitral regurgitation (MR) and its impact on symptoms, which was the aim of our study, has never been investigated. METHODS AND RESULTS: Consecutive patients with mild, moderate and severe MR were prospectively enrolled. Exclusion criteria were: chronic atrial fibrillation, valvular heart prosthesis, previous cardiac surgery. Clinical evaluation, blood sample tests, ECG and echocardiography with STE and MW measurement were performed. Patients were then divided into groups according to MR severity. Differences among the groups and predictors of symptoms (as NYHA class≥2) were explored as study endpoints. Overall, 180 patients were enrolled (60 mild,60 moderate,60 severe MR). LV GLS and global peak atrial longitudinal strain (PALS) reduced according to MR severity. Global constructive work (GCW) and global wasted work (GWW) significantly improved, while global work efficiency (GWE) reduced, in patients with moderate and severe MR. Among echocardiographic parameters, global PALS emerged as the best predictor of NYHA class (p < 0.001;area under curve,AUC = 0.7). CONCLUSIONS: MW parameters accurately describe the pathophysiology of MR, with initial attempt of LV increased contractility to compensate volume overload parallel to the disease progress, although with low efficacy, while global PALS is the most associated with the burden of MR symptoms.

Left Atrial Strain to Predict Postoperative Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery being associated with poorer outcomes. Revealing before the operation of left atrial subtle structural/functional abnormalities may help to identify patients at increased risk of POAF. We investigated the role of left atrial strain parameters by preoperative speckle tracking echocardiography as independent predictors of POAF in patients undergoing coronary artery bypass graft. METHODS: Consecutive patients undergoing isolated coronary artery bypass graft were prospectively enrolled at three Italian centers. All patients underwent transthoracic echocardiography before the operation. The occurrence of POAF up to discharge was monitored. RESULTS: Overall, a total of 310 patients were included. POAF was demonstrated in 103 patients (33%). At receiver operating characteristic curve analysis, lower global peak atrial longitudinal strain (PALS) values significantly predicted the risk of POAF (area under the curve, 0.74; P<0.001). The optimal cutoff value for the arrhythmia prediction was a global PALS value <28%, with a specificity of 86% and a sensitivity of 36%. The incidence of POAF was 51% in patients with global PALS <28% versus 14% in those with PALS ≥28% (P<0.001), with a POAF-free survival at Kaplan-Meier analysis of 45.4% and 85.7%, respectively (P<0.001). At multivariate analysis, a global PALS <28% carried a 3.6-fold higher risk of POAF (hazard ratio, 3.6 [95% CI, 2.2-5.9]; P<0.001). The risk increase was even higher when PALS <28% was associated with age ≥70 years (adjusted hazard ratio, 11.2 [4.7-26.6], P<0.001). CONCLUSIONS: A presurgery global PALS <28% is a specific parameter to stratify patients at increased risk of POAF after coronary artery bypass graft. This assessment can be useful to identify patients at higher arrhythmic risk in whom perioperative preventive strategies and stricter monitoring aimed at early diagnosing and treating POAF may be applied.

Arrhythmic mitral valve prolapse: a practical approach for asymptomatic patients.

Mitral valve prolapse (MVP) is usually regarded as a benign condition though the proportion of patients with a life-threatening arrhythmic MVP form remains undefined. Recently, an experts' consensus statement on arrhythmic MVP has proposed approaches for risk stratification across the spectrum of clinical manifestation. However, sudden cardiac death may be the first presentation, making clinicians focused to early unmasking this subset of asymptomatic patients. Growing evidence on the role of cardiac imaging in the in-deep stratification pathway has emerged in the last decade. Pathology findings have suggested the fibrosis of papillary muscles and inferobasal left ventricular wall as the malignant hallmark. Cardiac magnetic resonance, while of limited availability, allows the identification of this arrhythmogenic substrate. Therefore, speckle-tracking echocardiography may be a gateway to prompt referring patients to further advanced imaging investigation. Our review aims to summarize the phenotypic features linked to the arrhythmic risk and to propose an image-based algorithm intended to help stratifying asymptomatic MVP patients.

ECG/echo indexes in the diagnostic approach to amyloid cardiomyopathy: A head-to-head comparison from the AC-TIVE study.

BACKGROUND AND AIMS: The discordance between QRS voltages on electrocardiogram (ECG) and left ventricle (LV) wall thickness (LVWT) on echocardiogram (echo) is a recognized red flag (RF) of amyloid cardiomyopathy (AC) and can be measured by specific indexes. No head-to-head comparison of different ECG/echo indexes among subjects with echocardiographic suspicion of AC has yet been undertaken. The study aimed at evaluating the performance and the incremental diagnostic value of different ECG/echo indexes in this subset of patients. METHODS: Electrocardiograms of subjects with LV hypertrophy, preserved ejection fraction and ≥ 1 echocardiographic RF of AC participating in the AC-TIVE study, an Italian prospective multicenter study, were independently analyzed by two cardiologists. Low QRS voltages and 8 different ECG/echo indexes were evaluated. Cohort specific cut-offs were computed. RESULTS: Among 170 patients, 55 (32 %) were diagnosed with AC. Combination of low QRS voltages with interventricular septum ≥ 1,6 cm was the most specific (specificity 100 %, positive predictive value 100 %) ECG/echo index, while the ratio between the sum of all QRS voltages and LVWT <7,8 was the most sensitive and accurate (sensitivity 94 %, negative predictive value 97 %, accuracy 82 %). When the latter index was added to a model using easily-accessible clinical variables, the diagnostic accuracy for AC greatly increased (AUC from 0,84 to 0,95; p = 0,007). CONCLUSIONS: Among patients with non-dilated hypertrophic ventricles with normal ejection fraction and echocardiographic RF of AC, easily-measurable ECG/echo indexes, mainly when added to few clinical variables, can help the physician orient second level investigations. External validation of the results is warranted.

Multimodality Imaging for Selecting Candidates for CRT: Do We Have a Single Alley to Increase Responders?

Cardiac resynchronization therapy has evolved in recent years to provide a reduction of morbidity and mortality for many patients with heart failure. Its application and optimization is an evolving field and its use requires a multidisciplinary approach for patient and device selection, technical preprocedural planning, and optimization. While echocardiography has always been considered the first line for the evaluation of patients, additional imaging techniques have gained increasing evidence in recent years. Today different details about heart anatomy, function, dissynchrony can be investigated by magnetic resonance, cardiac computed tomography, nuclear imaging, and more, with the aim of obtaining clues to reach a maximal response from the electrical therapy. The purpose of this review is to provide a practical analysis of the single and combined use of different imaging techniques in the preoperative and perioperative phases of cardiac resynchronization therapy, underlining their main advantages, limitations, and information provided.

Real-world candidacy to mavacamten in a contemporary hypertrophic obstructive cardiomyopathy population.

AIMS: In the EXPLORER-HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real-world HOCM patients with those enrolled in EXPLORER-HCM and assessing their eligibility to treatment. METHODS AND RESULTS: We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.e. gradient ≥30 mmHg at rest or ≥50 mmHg after Valsalva manoeuvre or exercise) despite pharmacological or non-pharmacological therapy. Pharmacological or non-pharmacological therapy resolved LVOTO in 1044 (61.2%) of the 1706 HOCM patients under active follow-up, whereas 662 patients (38.8%) had persistent LVOTO. Compared to the EXPLORER-HCM trial population, these real-world HOCM patients were older (62.1 ± 14.3 vs. 58.5 ± 12.2 years, p = 0.02), had a lower body mass index (26.8 ± 5.3 vs. 29.7 ± 4.9 kg/m2 , p < 0.0001) and a more frequent history of atrial fibrillation (21.5% vs. 9.8%, p = 0.027). At echocardiography, they had lower left ventricular ejection fraction (LVEF, 66 ± 7% vs. 74 ± 6%, p < 0.0001), higher left ventricular outflow tract gradients at rest (60 ± 27 vs. 52 ± 29 mmHg, p = 0.003), and larger left atrial volume index (49 ± 16 vs. 40 ± 12 ml/m2 , p < 0.0001). Overall, 324 (48.9%) would have been eligible for enrolment in the EXPLORER-HCM trial and 339 (51.2%) for treatment with mavacamten according to European guidelines. CONCLUSIONS: Real-world HOCM patients differ from the EXPLORER-HCM population for their older age, lower LVEF and larger atrial volume, potentially reflecting a more advanced stage of the disease. About half of real-world HOCM patients were found eligible to mavacamten.

Left ventricular fibrosis as a main determinant of filling pressures and left atrial function in advanced heart failure.

AIMS: Advanced heart failure (AdHF) is characterized by variable degrees of left ventricular (LV) dysfunction, myocardial fibrosis, and raised filling pressures which lead to left atrial (LA) dilatation and cavity dysfunction. This study investigated the relationship between LA peak atrial longitudinal strain (PALS), assessed by speckle-tracking echocardiography (STE), and invasive measures of LV filling pressures and fibrosis in a group of AdHF patients undergoing heart transplantation (HTX). METHODS AND RESULTS: We consecutively enrolled patients with AdHF who underwent HTX at our Department. Demographic and basic echocardiographic data were registered, then invasive intracardiac pressures were obtained from right heart catheterization, and STE was also performed. After HTX, biopsy specimens from explanted hearts were collected to quantify the degree of LV myocardial fibrosis. Sixty-four patients were included in the study (mean age 62.5 ± 11 years, 42% female). The mean LV ejection fraction (LVEF) was 26.7 ± 6.1%, global PALS was 9.65 ± 4.5%, and mean pulmonary capillary wedge pressure (PCWP) was 18.8 ± 4.8 mmHg. Seventy-three % of patients proved to have severe LV fibrosis. Global PALS was inversely correlated with PCWP (R = -0.83; P < 0.0001) and with LV fibrosis severity (R = -0.78; P < 0.0001) but did not correlate with LVEF (R = 0.15; P = 0.2). Among echocardiographic indices of LV filling pressures, global PALS proved the strongest [area under the curve 0.955 (95% confidence interval 0.87-0.99)] predictor of raised (>18 mmHg) PCWP. CONCLUSION: In patients with AdHF, reduced global PALS strongly correlated with the invasively assessed LV filling pressure and degree of LV fibrosis. Such relationship could be used as non-invasive indicator for optimum patient stratification for therapeutic strategies.