Degenerative mitral regurgitation due to flail leaflet: sex-related differences in presentation, management, and outcomes.

BACKGROUND AND AIMS: Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes. METHODS: In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up. RESULTS: At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27-1.65), P < .001] but was higher in females [SMR 2.00 (1.67-2.38), P < .001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04-1.61), P = .02], cardiovascular mortality [adjusted HR 1.58 (1.14-2.18), P = .007], and heart failure [adjusted HR 1.36 (1.02-1.81), P = .04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P < .001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥ .09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16-1.47), P < .001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85-0.99), P = .036]. CONCLUSIONS: Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management.

Is Infectious Endocarditis Evolving into a Time-Dependent Diagnosis in the Contemporary Epidemiological Era? Emphasis on the Role of Echocardiography as a First-Line Diagnostic Approach.

Despite significant advances in understanding and outcomes in various domains of cardiology, the prognosis of infective endocarditis (IE) remains dismal. One of the main reasons may rely on an even more intricate diagnosis since epidemiology has shifted towards an aggressive infection, typically in older patients with the involvement of prosthetic valves and cardiovascular implantable electronic devices with earlier clinical presentation. In this novel setting, it is critical to avoid a delay in diagnosis that may delay subsequent adequate treatment, further complications, and ultimately poor clinical outcomes. Accordingly, based on the available data, we will examine the proper use of first-line echocardiography representing the first-line imaging method in patients with clinical suspicion of IE. We will focus on the following three crucial questions: (1) What is the threshold to start the echocardiographic diagnostic workup in stable patients? (2) Has infective endocarditis become a time-dependent diagnosis, even in stable patients? (3) What is the appropriate use of echocardiography in unstable patients? Finally, we propose a new mindset to improve the echocardiographic diagnostic workflow.

Exercise Stress Echocardiography for Stable Coronary Artery Disease: Succumbed to the Modern Conceptual Revolution or Still Alive and Kicking?

The modern conceptual revolution in managing patients with stable coronary artery disease (CAD), based on improvement in preventive and pharmacological therapy, advocates coronary artery revascularization only for smaller group of patients with refractory angina, poor left ventricular systolic function, or high-risk coronary anatomy. Therefore, our conventional wisdom about stress testing must be questioned within this new and revolutionary paradigm. Exercise stress echocardiography (ESE) is still a well-known technique for assessing known or suspected stable CAD, it is safe, accessible, and well-tolerated, and there is an widespread evidence base. ESE has been remarkably resilient throughout years of innovation in noninvasive cardiology. Its value is not to be determined over the short portion of diagnostic accuracy but mainly through its prognostic value evident in a wide range of patient subsets. It is coming very close to the modern profile of a leading test that should include, in addition to an essential accettable diagnostic and prognostic accuracy, qualities of low cost, no radiation exposure, and minor environmental traces. In this review, we will discuss advantages, diagnostic accuracy, prognostic value in general and special populations, cost-effectiveness, and changes in referral patterns of ESE in the modern era.

The Role of Stress Echocardiography in Valvular Heart Disease.

PURPOSE OF REVIEW: Stress echocardiography is recommended in valvular heart disease when there is a mismatch between resting transthoracic echocardiography findings and symptoms during activities of daily living. We describe the current methodology and the evidence supporting these applications. RECENT FINDINGS: The comprehensive stress echo assessment includes valve function (gradients and regurgitation), left ventricular global systolic and diastolic function, left atrial volume, pulmonary congestion, pulmonary arterial pressure, and right ventricular function, integrated with blood pressure response with cuff sphygmomanometer, chronotropic reserve with heart rate, and symptoms. Recent guidelines recommend the evaluation of asymptomatic severe or symptomatic non-severe mitral regurgitation or stenosis with exercise stress and suspected low-flow, low-gradient severe aortic stenosis with reduced ejection fraction with low dose (up to 20 mcg, without atropine) dobutamine stress. Prospective, large-scale studies based on a comprehensive protocol (ABCDE +) capturing the multiplicity of clinical phenotypes are needed to support stress echo-driven treatment strategies.

Early diagnosis of cardiomyopathies by cardiac magnetic resonance. Overview of the main criteria.

Cardiomyopathies (CMPs) are diseases of the heart muscle. They include a variety of myocardial disorders that manifest with various structural and functional phenotypes and are frequently genetic. Myocardial disease caused by known cardiovascular causes (such as hypertension, ischemic heart disease, or valvular disease) should be distinguished from CMPs for classification and management purposes. Identification of various CMP phenotypes relies primarily upon echocardiographic evaluation. In selected cases, cardiac magnetic resonance imaging (CMR) or computed tomography may be useful to identify and localize fatty infiltration, inflammation, scar/fibrosis, focal hypertrophy, and better visualize the left ventricular apex and right ventricle.  CMR imaging has emerged as a comprehensive tool for the diagnosis and follow-up of patients with CMPs. The accuracy and reproducibility in evaluating cardiac structures, the unique ability of non-invasive tissue characterization and the lack of ionizing radiation, make CMR very attractive as a potential "all-in-one technique". Indeed, it provides valuable data to confirm or establish the diagnosis, screen subclinical cases, identify aetiology, establish the prognosis. Additionally, it provides information for setting a risk stratification (based on evaluation of proved independent prognostic factors as ejection fraction, end-systolic-volume, myocardial fibrosis) and follow-up. Last, it helps to monitor the response to the therapy. In this review, the pivotal role of CMR in the comprehensive evaluation of patients with CMP is discussed, highlighting the key features guiding differential diagnosis and the assessment of prognosis.

Incremental Value of Renal Dysfunction Addition to the CHA2DS2-Vasc Score for Mortality Prediction in Patients with Acute Coronary Syndrome.

INTRODUCTION: This study analyzes the usefulness of the CHA2DS2-VASc score for mortality prediction in patients with acute coronary syndromes (ACSs) and evaluates if the addition of renal functional status could improve its predictive accuracy. METHODS: CHA2DS2-VASc score was calculated by using both the original scoring system and adding renal functional status using 3 alternative renal dysfunction definitions (CHA2DS2-VASc-R1: eGFR <60 mL/min/1.73 mq = 1 point; CHA2DS2-VASc-R2: eGFR <60 mL/min/1.73 mq = 2 points; and CHA2DS2-VASc-R3: eGFR <60 mL/min/1.73 mq = 1 point, <30 mL/min/1.73 mq = 2 points). Inhospital mortality (IHM) and post-discharge mortality (PDM) were recorded, and discrimination of the various risk models was evaluated. Finally, the net reclassification index (NRI) was calculated to compare the mortality risk classification of the modified risk models with that of the original score. RESULTS: Nine hundred and eight ACS patients (median age 68 years, 30% female, 51% ST-elevation) composed the study population. Of the 871 patients discharged, 865 (99%) completed a 12-month follow-up. The IHM rate was 4.1%. The CHA2DS2-VASc score demonstrated a good discriminative performance for IHM (C-statistic 0.75). Although all the eGFR-modified risk models showed higher C-statistics than the original model, a statistically significant difference was observed only for CHA2DS2-VASc-R3. The PDM rate was 4.5%. The CHA2DS2-VASc C-statistic for PDM was 0.75, and all the modified risk models showed significantly higher C-statistics values than the original model. The NRI analysis showed similar results. CONCLUSIONS: CHA2DS2-VASc score demonstrated a good predictive accuracy for IHM and PDM in ACS patients. The addition of renal dysfunction to the original score has the potential to improve identification of patients at the risk of death.

Prevalence of left atrial thrombus by real time three-dimensional echocardiography in patients undergoing electrical cardioversion of atrial fibrillation: A contemporary cohort study.

BACKGROUND: The prevalence of left atrial thrombi in patients scheduled for electrical cardioversion (ECV) of atrial fibrillation (AF) remains unknown in contemporary real-life practice. METHODS AND RESULTS: Patients scheduled for ECV underwent transesophageal echocardiography (TEE) regardless of AF duration and type of anticoagulant. Of 277 consecutive patients (65% men, mean age 71 ± 10 years, CHA2 DS2 -VASc 3.1 ± 1.4), 92 were on direct oral anticoagulants (DOACs) and 99 on antivitamin K (AVK) oral agents for at least 3 weeks before and 4 after ECV. Eighty-five patients with paroxysmal AF on low-molecular-weight heparin were also considered. Real time three-dimensional TEE detected left atrial appendage (LAA) thrombus in 7% of patients, without significant difference among three groups (P = .334). Anticoagulation was ineffective in eight patients on AVK oral agents, two of them had thrombus. Eight patients assumed incorrectly DOACs, four of them had thrombus. Among the 175 patients on effective anticoagulation, five showed thrombus, three on AVK oral agents, and two on DOACs (P = .716). Effective anticoagulation was associated with reduced risk of thrombosis (OR: 0.16, 95%CI: 0.06-0.45, P = .001). In patients with correct anticoagulation, predictors of thrombus were CHA2 DS2 VASc (for each point of increment OR: 1.97, 95%CI: 1.08-3.61, P = .029), low left ventricular ejection fraction (OR: 0.92, 95%CI: 0.86-0.99, P = .026), and degree of spontaneous echo-contrast (for each point increase OR: 10, 95%CI: 2-39, P < .0001). CONCLUSION: Patients with AF, on effective anticoagulation, had a prevalence of thrombus not negligible regardless of type of anticoagulant. TEE is prudent before ECV and mandatory if unsuccessful anticoagulation is proved or suspected.

Active cancer and cardiac surgery: Possible scenarios in patient decision-making.

Heart disease and cancer are often found simultaneously in the same patient, and may require cardiac and non-cardiac surgery. Cancer may be part of the past medical history; in other cases the presence of an active malignancy makes the clinical management more complex. No general evidence-based recommendations are available to help in the decision-making process. Because of the lack of specific guidelines we provided a series of possible scenarios describing not unusual cases. We focused on cases where the concomitant presence of heart disease and active malignancies involved a multidisciplinary team. Four real patients with active cancer referred to our Center were assessed. Three of them had valve disease requiring cardiac surgery. Defining the timing of surgery and choosing the surgical approach required a careful and comprehensive evaluation. In the last case, the complicated balance between the thrombotic and the hemorrhagic risk involved difficult decision. Several critical points, which characterized the management of this kind of patients, were identified. In particular, the hemodynamic status, the type and stage of the tumor, the need for cancer therapy, as well as the comorbidities of the patient, had to be taken into account. This narrative review shows the importance of submitting every challenging case to the assessment of a multidisciplinary team, which involves different clinical figures, in order to guarantee the most comprehensive evaluation. When clinical management deviates from the general recommendations, an individualized approach should be used.

Stage A Heart Failure: Modern Strategies for an Effective Prevention.

Stage A heart failure (HF) patients do not show HF symptoms or any structural heart disease but are at risk of HF development. Cardiovascular risk factors (hypertension, diabetes, metabolic syndrome, sedentary lifestyle, poor diet, and exposure to cardiotoxic agents) characterize subjects affected by stage A HF. It is essential to identify these subjects early and ensure that, despite being asymptomatic, they grasp the importance of undertaking correct lifestyle and therapeutic interventions. A careful stratification of asymptomatic subject's risk profile is needed to adopt proper preventive strategies and to set individualized therapeutic targets that avoid progression to advanced stages of HF.

Optimal Use of Echocardiography in Management of Thrombosis After Anterior Myocardial Infarction.

Despite advancement in therapy and management, left ventricular thrombus (LVT) after anterior myocardial infarction (MI) is sporadically encountered and remains associated with a very high risk of major cardiovascular events and mortality. Cardiac magnetic resonance (CMR) is considered the gold standard technique for LVT detection, but it is a time-consuming and expensive test not available in all centers, especially when repeated examinations are necessary. Transthoracic echocardiography represents a useful tool to screen for LVT and to identify predictors of high risk of developing LVT. The advances in ultrasound technology and the use of contrast agents may potentially help clinicians to identify LVT and the use of sequential echocardiography for each patient with acute MI complicated by LVT may provide an opportunity to quantify regression and its correlation with outcomes to tailor the management of these patients. Hence, this narrative review focuses on the added value of echocardiographic-guided LVT management in patients with recent anterior MI to reduce mortality and morbidity excess related to LVT based on current evidence.

Prognostic utility of quantitative offline 2D-echocardiography in hospitalized patients with COVID-19 disease.

PURPOSE: To assess the prognostic utility of quantitative 2D-echocardiography, including strain, in patients with COVID-19 disease. METHODS: COVID-19-infected patients admitted to the San Paolo University Hospital of Milan that underwent a clinically indicated echocardiographic examination were included in the study. To limit contamination, all measurements were performed offline. Quantitative measurements were obtained by an operator blinded to the clinical data. RESULTS: Among the 49 patients, nonsurvivors (33%) had worse respiratory parameters, index of multiorgan failure, and worse markers of lung involvement. Right ventricular (RV) dysfunction (as assessed by conventional and 2-dimensional speckle tracking) was a common finding and a powerful independent predictor of mortality. At the ROC curve analyses, RV free wall longitudinal strain (LS) showed an AUC 0.77 ± 0.08 in predicting death, P = .008, and global RV LS (RV-GLS) showed an AUC 0.79 ± 0.04, P = .004. This association remained significant after correction for age (OR = 1.16, 95%CI 1.01-1.34, P = .029 for RV free wall LS and OR = 1.20, 95%CI 1.01-1.42, P = .033 for RV-GLS), for oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen (OR = 1.28, 95%CI 1.04-1.57, P = .021 for RV free wall-LS and OR = 1.30, 95%CI 1.04-1.62, P = .020 for RV-GLS) and for the severity of pulmonary involvement measured by a computed tomography lung score (OR = 1.27, 95%CI 1.02-1.19, P = .034 for RV free wall LS and OR = 1.30, 95%CI 1.04-1.63, P = .022 for RV-GLS). CONCLUSIONS: In patients hospitalized with COVID-19, offline quantitative 2D-echocardiographic assessment of cardiac function is feasible. Parameters of RV function are frequently abnormal and have an independent prognostic value over markers of lung involvement.

Degree of left ventricular dilatation at end-diastole: Correlation and prognostic utility of quantitative volumes by 2D-echocardiography versus linear dimensions in patients with asymptomatic aortic regurgitation.

BACKGROUND: Guideline recommendations for aortic valve replacement (AVR) in asymptomatic patients with chronic aortic regurgitation (AR) have historically focused on linear dimensions without normalization for the body surface area (BSA). Values for grading the severity of end-diastolic volume dilatation by 2D echocardiography remain to be established. METHODS AND RESULTS: We retrospectively analyzed 543 consecutive asymptomatic patients with pure chronic moderate/severe AR (mean age 66 ± 17 years, 37.7% males). Applying the ASE/EACVI guidelines, BSA-indexed LV end-diastolic volume (LVEDVi) and indexed LV end-diastolic diameter (LVEDDi) were assessed. Then, we identified 192 patients with at least mild LV end-diastolic dilatation by volumetric or linear measurements. The outcome endpoint was the combination of cardiac death, hospitalization for acute heart failure or AVR during a median follow-up of 4.5 ± 3.6 years. Multivariable Cox regression analyses including age, LV ejection fraction (EF) and AR severity showed an independent prognostic value of the LVEDDi and LVEDVi (P < .001 and P < .01, respectively). Congruent severe LVEDDi and LVEDVi dilatation was associated with a higher event rate compared to discordant severe LV end-diastolic dilatation or nonsevere LV dilatation (P = .001) even after landmark analysis (P = .02). In patients with EF > 50%, only the LVEDVi showed and independent prognostic value (P < .001). CONCLUSIONS: In a cohort of asymptomatic patients with AR, the presence of severe LV volume and diameter dilatation on the basis of the cutoff values proposed by current recommendations and normalized for BSA may be instrumental in the identification of patients at increased risk of clinical progression regardless of EF.

Remodeling classification system considering left ventricular volume in patients with aortic valve stenosis: Association with adverse cardiovascular outcomes.

BACKGROUND: To assess prevalence and clinical implications of left ventricular (LV) remodeling considering: LV volume, mass and relative wall thickness at the time of aortic valve stenosis diagnosis. METHODS AND RESULTS: We retrospectively analyzed 343 patients (age 79.2 ± 9.5 years, 48.1% males) with functional aortic valve area (AVA) ≤ 1.5 cm2 . LV geometric patterns and clinical outcomes (combined death, cardiac hospitalization, aortic valve replacement [AVR]) were evaluated. According to the new LV remodeling classification, 4.9% had normal geometry, 7.5% concentric remodeling, 39.3% concentric hypertrophy (LVH), 22.4% mixed LVH, 12.5% dilated LVH, 3.2% eccentric LVH and 4.3% eccentric remodeling, 5.5% had not classifiable LVH. Indexed stroke volume (SVi) was higher in patients with concentric LVH (40.3 ± 11.9 mL/m2 ) and mixed LVH (41.6 ± 13.4 mL/m2 ) and lower in patients with eccentric LVH (24.9 ± 7.7 mL/m2 ), concentric (36.6 ± 12.7 mL/m2 ) and eccentric remodeling (34.9 ± 9.5 mL/m2 ), P = 0.003. During a median follow-up of 2.2 years, 260 (75.8%) had the combined end point. A significant association between the combined end point and LV dilation (P = 0.010) or LV remodeling patterns (P = 0.0001) was found. After multivariable adjustment for AVR, concentric remodeling (HR 3.12, IC 95% 1.14-8.55; P = 0.02) and dilated LVH (HR 3.48, IC 95% 1.31-9.27; P = 0.01) were strongly associated with death or cardiac hospitalizations. CONCLUSIONS: In patients with AVA ≤ 1.5 cm2 , when the new LV remodeling classification system is applied, only a minority had normal geometry and less than half had "classic" concentric LVH or remodeling. LV volume dilatation is frequent and associated with adverse outcome. Concentric remodeling, eccentric remodeling, dilated LVH had the worst noninvasive hemodynamic profile and prognosis.

New classification of geometric patterns considering left ventricular volume in patients with chronic aortic valve regurgitation: Prevalence and association with adverse cardiovascular outcomes.

BACKGROUND: Left ventricular (LV) remodeling due to aortic regurgitation (AR) often leads to maladaptive responses. We assessed the prevalence and clinical implications of LV remodeling considering LV volume, mass, and relative wall thickness at the time of AR diagnosis. METHODS AND RESULTS: Between 2008 and 2017, 370 consecutive patients (mean age 67.3 ± 16.1 years, 56.5% males), with moderate or severe AR, were retrospectively analyzed. LV geometric patterns and clinical outcomes (cardiovascular death, hospitalization for heart failure, or aortic valve replacement) were evaluated. LV dilatation (LV end-diastolic volume >75 mL/m2 ) was present in 228 patients (61.6%). Applying the new LV remodeling classification system, 40 (10.8%) patients had normal geometry, 14 (3.8%) concentric remodeling, 43 (11.6%) concentric hypertrophy (LVH), 45 (12.2%) indeterminate LVH, 38 (10.3%) mixed LVH, 93 (25.1%) dilated LVH, 54 (14.6%) eccentric LVH, and 43 (11.6%) eccentric remodeling. During a median follow-up of 3.48 years (25th-75th percentile 0.91-5.57), 97 (26.2%) had the combined endpoint. LV dilation (P < 0.001), LVH (P < 0.001), and LV remodeling patterns were significantly associated with the combined endpoint. After multivariable adjustment for age, EF, aortic stenosis, CAD history, and moderate mitral regurgitation, dilated LVH (HR 7.61, IC 95% 1.82-31.80; P = 0.005) and eccentric LVH (HR 7.91, IC 95% 1.82-34.38; P = 0.006) were associated with adverse outcome compared to eccentric remodeling, that showed the best event-free survival rate. CONCLUSIONS: In a contemporary cohort of patients with AR, applying the new LV remodeling classification system, only a minority had normal geometry. Dilated LVH and eccentric LVH showed distinct outcome penalty after adjustment for confounders.

Imaging functional stress test for stable chest pain symptoms in patients at low pretest probability of coronary artery disease: Current practice and long-term outcome.

BACKGROUND: Stress testing in patients with low pretest probability (PTP) of coronary artery disease (CAD) has become an increasing practice, potentially leading to underestimation of its true clinical value. Our aim was to describe the current use of most employed imaging functional tests and their prognostic value. METHODS AND RESULTS: We selected patients with low PTP of CAD (CAD consortium clinical score < 15%) who underwent exercise or dipyridamole stress echocardiography or single photon emission computed tomography for suspected angina. Main exclusions were age < 45, known CAD, and abnormal rest wall motion. Of the 2279 subjects undergoing stress test, 883 (39%) had low PTP, and 91 (10.3%) had a positive test for ischemia. After a median follow-up of 5.8 years, 36 patients had events (21 died, 14 had nonfatal myocardial infarction). The percentage of events in the abnormal and normal stress test groups were similar (5 [5.5%] vs 31 [3.9%], P = ns), as the annualized event rate (0.87% vs 0.62%, P = ns). Age was the only variable associated with outcome in the regression analysis (hazard ratio 1.072, 95% CI 1.034-1.113, P < 0.001). An abnormal result was not associated with worse outcome in each of the subgroups of functional tests. CONCLUSIONS: In our geographical area, a considerable proportion of patients undergoing imaging functional tests for stable chest pain have a low estimated PTP of CAD. Of these, 1 in 10 resulted positive for inducible ischemia. However, none of the most common imaging functional tests, single photon emission computed tomography (SPECT), and stress echocardiography offer prognostic information in these patients.

The MIDA Mortality Risk Score: development and external validation of a prognostic model for early and late death in degenerative mitral regurgitation.

Aims: In degenerative mitral regurgitation (DMR), lack of mortality scores predicting death favours misperception of individual patients' risk and inappropriate decision-making. Methods and results: The Mitral Regurgitation International Database (MIDA) registries include 3666 patients (age 66 ± 14 years; 70% males; follow-up 7.8 ± 5.0 years) with pure, isolated, DMR consecutively diagnosed by echocardiography at tertiary (European/North/South-American) centres. The MIDA Score was derived from the MIDA-Flail-Registry (2472 patients with DMR and flail leaflet-Derivation Cohort) by weighting all guideline-provided prognostic markers, and externally validated in the MIDA-BNP-Registry (1194 patients with DMR and flail leaflet/prolapse-Validation Cohort). The MIDA Score ranged from 0 to 12 depending on accumulating risk factors. In predicting total mortality post-diagnosis, the MIDA Score showed excellent concordance both in Derivation Cohort (c = 0.78) and Validation Cohort (c = 0.81). In the whole MIDA population (n = 3666 patients), 1-year mortality with Scores 0, 7-8, and 11-12 was 0.4, 17, and 48% under medical management and 1, 7, and 14% after surgery, respectively (P < 0.001). Five-year survival with Scores 0, 7-8, and 11-12 was 98 ± 1, 57 ± 4, and 21 ± 10% under medical management and 99 ± 1, 82 ± 2, and 57 ± 9% after surgery (P < 0.001). In models including all guideline-provided prognostic markers and the EuroScoreII, the MIDA Score provided incremental prognostic information (P ≤ 0.002). Conclusion: The MIDA Score may represent an innovative tool for DMR management, being able to position a given patient within a continuous spectrum of short- and long-term mortality risk, either under medical or surgical management. This innovative prognostic indicator may provide a specific framework for future clinical trials aiming to compare new technologies for DMR treatment in homogeneous risk categories of patients.

Biomarkers of lung congestion and injury in acute heart failure.

Acute heart failure (AHF) classification and management are primarily based on lung congestion and/or hypoperfusion. The quantification of the vascular and tissue lung damage is not standard practice though biomarkers of lung injury may play a relevant role in this context. Haemodynamic stress promotes alveolar and vascular derangement with loss of functional units, impaired lung capillary permeability and fluid swelling. This culminates in a remodelling process with activation of inflammatory and cytokines pathways. Four families of lung surfactant proteins (i.e., SP-A, SP-B, SP-C, and SP-D), essential for the membrane biology and integrity are released by alveolar type II pneumocites. With deregulation of fluid handling and gas exchange pathways, SPs become sensitive markers of lung injury. We report the pathobiology of lung damage; the pathophysiological and clinical implications of alveolar SPs along with the newest evidence for some classical HF biomarkers that have also shown to reflect a vascular and/or a tissue lung-related activity.

Outpatient tricuspid regurgitation in the community: Clinical context and outcome.

BACKGROUND AND AIMS: Epidemiology of tricuspid regurgitation (TR) is poorly known and its burden in the community is challenging to define. We aimed to evaluate the prevalence of TR in a geographically defined area and its outcome, in particular overall survival and hospitalization, considering different clinical contexts. METHODS: We retrospectively analyzed consecutive outpatients referred between 2006 and 2013 for echocardiography and clinical evaluation. Patients with at least moderate TR were included and five different clinical settings were defined: concomitant significant left-sided valvular heart disease (LVHD-TR), heart failure (HF-TR), previous open-heart valvular surgery (postop-TR), pulmonary hypertension (PHTN-TR) and isolated TR (isolated-TR). Primary endpoint was a composite outcome of all-cause mortality or first hospitalization for HF. RESULTS: Of 6797 consecutive patients with a clinical visit and echocardiograms performed in routine practice in a geographically defined community, moderate or severe TR was found in 4.8% of patients (327) . During median follow-up of 6.1 years, TR severity was a determinant of event-free survival. Analyzed for each clinical subset, eight-year event-free survival was 87 ± 7% for postop-TR subgroup, 75 ± 7% for isolated-TR, 67 ± 6% for PHTN-TR, 58 ± 6% for LHVD -TR and 52 ± 11% for HF-TR. CONCLUSION: Moderate or more TR is a notable finding in the community and has impact on event-free survival in all clinical settings, with the worst outcomes when associated with relevant left-sided valvular heart disease and HF.

Indexing left ventricular end-systolic dimension to body size: Association with mortality in patients with degenerative mitral regurgitation.

AIMS: In patients with degenerative mitral regurgitation (DMR), left ventricular (LV) dysfunction is associated with increased risk of heart failure and excess mortality. LV end-systolic diameter (LVESD) is an established trigger for intervention, yet recommended LVESD thresholds apply poorly to patients with small body size. Whether LV normalization to body surface area (BSA) may be used as a trigger for DMR correction is unknown. We examined the link between LVESD index (LVESDi) and outcome in DMR to identify appropriate thresholds for excess mortality. METHODS AND RESULTS: This study focuses on 2753 consecutive patients with DMR due to flail leaflets diagnosed in tertiary centres from Europe and the United States, with prospective echocardiographic measurement of LVESD and BSA and long-term follow-up. The primary endpoint was mortality after diagnosis under conservative management. Secondary endpoints were mortality under conservative and surgical management and postoperative mortality of patients who underwent surgery. The optimal LVESDi cut-off for mortality prediction was 20 mm/m2. Irrespective of management type, 10-year survival was lower with LVESDi ≥20 mm/m2 than with LVESDi <20 mm/m2 (both p < 0.001). After covariate adjustment, LVESDi ≥20 mm/m2 was independently predictive of mortality under conservative management (adjusted hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.15-1.75), and with conservative and surgical management (adjusted HR 1.34, 95% CI 1.17-1.54). LVESDi remained associated with poorer postoperative outcome in patients who underwent intervention. LVESDi showed higher incremental predictive value over the baseline model compared to LVESD. The association between LVESDi ≥20 mm/m2 and outcome was consistent in subgroups of patients with DMR. CONCLUSIONS: In severe DMR due to flail leaflets, LVESDi is a marker of risk additive and incremental to LVESD. Its use in clinical practice should lead to earlier referral to mitral valve surgery and improved long-term outcome.