Degenerative Mitral Regurgitation Outcomes in Asian Compared With European-American Institutions.

Background: Clinical outcome and interventional thresholds for degenerative mitral regurgitation (DMR) were developed in studies of patients at European and American institutions (EAIs), but little is known about patients at Asian institutions (AsIs). Objectives: This study sought to contrast DMR presentation/management/outcomes of AsI patients vs EAI patients. Methods: Patients with DMR due to flail leaflet from Hong Kong and Singapore (AsI cohort, n = 737) were compared with EAI patients (n = 682) enrolled in the MIDA (Mitral regurgitation International Database) registry with similar eligibility criteria. Results: AsI patients presented similar DMR lesion/consequences vs EAI patients, but they were younger, with fewer symptoms (74% vs 44% Class I), more sinus rhythm (83% vs 69%), and lower EuroSCORE II (European System for Cardiac Operative Risk Evaluation II) (0.9 ± 0.5 vs 1.4 ± 1.5; all P < 0.0001). Imaging showed smaller absolute left atrial/ventricular dimensions in AsI patients, belying cardiac dilatation with larger body surface area-indexed diameters (all P < 0.01). Surgical/interventional mitral repair was similarly predominant (90% vs 91%; P = 0.47), and early repair was similarly beneficial (for AsI patients, adjusted HR: 0.28; 95% CI: 0.16-0.49; for EAI patients, HR: 0.32; 95% CI: 0.20-0.49; both P < 0.0001). However, AsI patients underwent fewer interventions (55% ± 2% vs 77% ± 2% at 1 year; P < 0.0001) and incurred excess mortality (adjusted HR: 1.60 [95% CI: 1.13-2.27] vs EAI patients; P = 0.008) at long-term postdiagnosis. Propensity score matching (434 patient pairs), which balanced all clinical characteristics, confirmed that there was undertreatment and excess mortality in the long term in AsI patients with DMR (P < 0.0001). Conclusions: Imaging may underestimate volume overload in AsI patients due to smaller cardiac cavities related to smaller body size compared with EAI patients with similar mitral lesions and DMR severity. AsI patients enjoy similar mitral repair predominance and early intervention benefits but undergo fewer mitral interventions than EAI patients and incur subsequent excess mortality, suggesting the need to account for imaging and cultural specificity to improve DMR outcomes worldwide.

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.

Survival loss linked to guideline-based indications for degenerative mitral regurgitation surgery.

AIMS: Operating on patients with severe degenerative mitral regurgitation (DMR) is based on ACC/AHA or ESC/EACTS-guidelines. Doubts persist on best surgical indications and their potential association with postoperative survival loss. We sought to investigate whether guideline-based indications lead to late postoperative survival loss in DMR-patients. METHODS AND RESULTS: : We analyzed outcome of 2833 patients from the MIDA-registry undergoing surgical correction of DMR. Patients were stratified by surgical indications: Class-I-trigger (symptoms, left ventricular end-systolic diameter≥40mm, or left ventricular ejection fraction<60%, n=1677), isolated-Class-IIa-trigger (atrial fibrillation [AF], pulmonary hypertension [PH], or left atrial diameter≥55mm, n=568), or no-trigger (n=588). Postoperative survival was compared after matching for clinical differences. Restricted-mean-survival time (RMST) was analyzed. During a median 8.5-year follow-up, 603 deaths occurred. Long-term postoperative survival was lower with Class-I-trigger than in Class-IIa-trigger and no-trigger (71.4±1.9%, 84.3±2.3%, 88.9±1.9% at 10 years, p<0.001). Having at least one Class-I-criterion led to excess mortality (p<0.001), while several Class-I-criteria conferred additional death-risk (HR:1.53, 95%CI:1.42-1.66). Isolated-Class-IIa-triggers conferred an excess mortality risk versus those without (HR:1.46, 95%CI:1.00-2.13, p=0.05). Among these patients, isolated-PH led to decreased postoperative-survival versus those without (83.7%±2.8% vs. 89.3%±1.6%, p=0.011), with the same pattern observed for AF (81.8%±5.0% vs. 88.3%±1.5%, p=0.023). According to RMST-analysis, compare to those operated on without triggers, operating on Class-I-trigger patients led to 9.4-month survival-loss (p<0.001) and operating on isolated-Class-IIa-trigger patients displayed 4.9-month survival loss (p=0.001) after 10-years. CONCLUSIONS: : Waiting for the onset of Class-I or isolated-Class-IIa-triggers before operating on DMR patients is associated with postoperative survival loss. These data encourage an early surgical-strategy.

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.

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.

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.

Case Report: A rare homozygous patient affected by TTR systemic amyloidosis with a prominent heart involvement.

Hereditary transthyretin amyloidosis is a severe, adult-onset autosomal dominant inherited systemic disease predominantly affecting the peripheral and autonomic nervous system, heart, kidney, and the eyes. We present a case of a Caucasian 65-year-old man with cardiac amyloidosis and the homozygous mutation Val142Ile (classically, Val122Ile) in the transthyretin gene. We provide a genotype-phenotype correlation regarding the genetic status of both heterozygous and homozygous individuals and their clinical conditions at the time of genetic testing.

Organization and Activity of Italian Echocardiographic Laboratories: A Survey of the Italian Society of Echocardiography and Cardiovascular Imaging.

Background: The Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand better how different echocardiographic modalities are used and accessed in Italy. Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved via an electronic survey based on a structured questionnaire, uploaded on the SIECVI website. Results: Data were obtained from 228 echocardiographic laboratories: 112 centers (49%) in the northern, 43 centers (19%) in the central, and 73 (32%) in the southern regions. During the month of observation, we collected 101,050 transthoracic echocardiography (TTE) examinations performed in all centers. As concern other modalities there were performed 5497 transesophageal echocardiography (TEE) examinations in 161/228 centers (71%); 4057 stress echocardiography (SE) examinations in 179/228 centers (79%); and examinations with ultrasound contrast agents (UCAs) in 151/228 centers (66%). We did not find significant regional variations between the different modalities. The usage of picture archiving and communication system (PACS) was significantly higher in the northern (84%) versus central (49%) and southern (45%) centers (P < 0.001). Lung ultrasound (LUS) was performed in 154 centers (66%), without difference between cardiology and noncardiology centers. The evaluation of left ventricular (LV) ejection fraction was evaluated mainly using the qualitative method in 223 centers (94%), occasionally with the Simpson method in 193 centers (85%), and with selective use of the three-dimensional (3D) method in only 23 centers (10%). 3D TTE was present in 137 centers (70%), and 3D TEE in all centers where TEE was done (71%). The assessment of LV diastolic function was done routinely in 80% of the centers. Right ventricular function was evaluated using tricuspid annular plane systolic excursion in all centers, using tricuspid valve annular systolic velocity by tissue Doppler imaging in 53% of the centers, and using fractional area change in 33% of the centers. When we divided into cardiology (179, 78%) and noncardiology (49, 22%) centers, we found significant differences in the SE (93% vs. 26%, P < 0.001), TEE (85% vs. 18%), UCA (67% vs. 43%, P < 0001), and STE (87% vs. 20%, P < 0.001). The incidence of LUS evaluation was similar between the cardiology and noncardiology centers (69% vs. 61%, P = NS). Conclusions: This nationwide survey demonstrated that digital infrastructures and advanced echocardiography modalities, such as 3D and STE, are widely available in Italy with a notable diffuse uptake of LUS in the core TTE examination, a suboptimal diffusion of PACS recording, and conservative use of UCA, 3D, and strain. There are significant differences between northern and central-southern regions and echocardiographic laboratories that pertain to the cardiac unit. This inhomogeneous distribution of technology represents one of the main issues that must be solved to standardize the practice of echocardiography.

Use and Implications of Echocardiography in the Hemodynamic Assessment of Cardiogenic Shock.

Cardiogenic shock (CS) is a complex multisystem syndrome due to pump failure, associated with high mortality and morbidity. Its hemodynamic characterization is key to the diagnostic algorithm and management. Pulmonary artery catheterization is the gold standard for the left and right hemodynamic evaluation, but some concerns exist for invasivity and untoward mechanical and infective complications. Transthoracic echocardiography is a robust noninvasive diagnostic tool for hemodynamic multiparametric assessment that well applies to the management of CS. Its applications expand from etiology definition to the choice of therapeutic intervention and their monitoring. The present review aims at detailing the role of ultrasounds in CS emphasizing the clinical implications of combining cardiac and non-cardiac ultrasounds examinations that may correlate with prognosis.

ABCDEG Stress Echocardiography in Aortic Stenosis.

Rest and stress echocardiography (SE) plays a pivotal role in the evaluation of valvular heart disease. The use of SE is recommended in valvular heart disease when there is a mismatch between resting transthoracic echocardiography findings and symptoms. In aortic stenosis (AS), rest echocardiographic analysis is a stepwise approach that begins with the evaluation of aortic valve morphology and proceeds to the measurement of the transvalvular aortic gradient and aortic valve area (AVA) using continuity equations or planimetry. The presence of the following three criteria suggests severe AS: AVA < 1.0 cm2, a peak velocity > 4.0 m/s, or a mean gradient > 40 mmHg. However, in approximately one in three cases, we can observe a discordant AVA < 1 cm2 with a peak velocity < 4.0 m/s or a mean gradient <40 mmHg. This is due to reduced transvalvular flow associated with LV systolic dysfunction (LVEF < 50%) defined as "classical" low-flow low-gradient (LFLG) AS or normal LVEF "paradoxical" LFLG AS. SE has an established role in evaluating LV contractile reserve (CR) patients with reduced LVEF. In classical LFLG AS, LV CR distinguished pseudo-severe AS from truly severe AS. Some observational data suggest that long-term prognosis in asymptomatic severe AS may not be as favorable as previously thought, offering a window of opportunity for intervention prior to the onset of symptoms. Therefore, guidelines recommend evaluating asymptomatic AS with exercise stress in physically active patients, particularly those younger than 70 years, and symptomatic classical LFLG severe AS with low-dose dobutamine SE. A comprehensive SE assessment includes evaluating valve function (gradients), the global systolic function of the LV, and pulmonary congestion. This assessment integrates considerations of blood pressure response, chronotropic reserve, and symptoms. StressEcho 2030 is a prospective, large-scale study that employs a comprehensive protocol (ABCDEG) to analyze the clinical and echocardiographic phenotypes of AS, capturing various vulnerability sources which support stress echo-driven treatment strategies.

Long-Term Effects of Sacubitril-Valsartan on Cardiac Remodeling: A Parallel Echocardiographic Study of Left and Right Heart Adaptive Response.

Sacubitril/Valsartan (S/V) carries potential anti-remodeling properties, however long-term effects and biventricular adaptive response are poorly described. 76 HFrEF patients who underwent progressive uptitration of S/V, completed the annual scheduled follow-up. After a median follow-up of 11 (8-13) months, left ventricular (LV) reverse remodeling (RR) is defined as (1) absolute increase in LV ejection fraction (EF) ≥ 10% or LVEF ≥ 50% at follow-up and (2) decrease in indexed LV end-diastolic diameter (LVEDDi) of at least 10% or indexed LVEDDi ≤ 33 mm/m2, occurred in 27.6%. Non-ischemic etiology, shorter duration of HF, and absence of a history of AF were independently associated with LVRR (p < 0.05). TAPSE and TAPSE/PASP, a non-invasive index of right ventricular (RV) coupling to the pulmonary circulation, significantly improved at follow-up (0.45 vs. 0.56, p = 0.02). 41% of patients with baseline RV dysfunction obtained favorable RV remodeling despite only a moderate correlation between RV and LV function was observed (r = 0.478, p = 0.002). Our data point to a potential long-term reverse global remodeling effect by S/V, especially in patients who start S/V at an early stage of the disease, and focus our attention on a possible direct effect of the drug in synergistic hemodynamics between RV and pulmonary circulation.

Arrhythmogenic Mitral Valve Prolapse and Sudden Cardiac Death: An Update and Current Perspectives.

Mitral valve prolapse (MVP) affects about 2% to 3% of the general population, mostly women, and is the most common cause of primary chronic mitral regurgitation (MR) in western countries. The natural history is heterogeneous and widely determined by the severity of MR. Although most patients remain asymptomatic with a near-normal life expectancy, approximately 5% to 10 % progress to severe MR. As largely recognized, left ventricular (LV) dysfunction due to chronic volume overload per se identifies a subgroup at risk of cardiac death. However, there is rising evidence of a link between MVP and life threating ventricular arrhythmias (VAs)/sudden cardiac death (SCD) in a small subset of middle-aged patients without significant MR, heart failure and remodeled hearts. The present review focuses on the underlying mechanism of electric instability and unexpected cardiac death in this subset of young patients, from the myocardial scarring of the LV infero-lateral wall due to mechanical stretch exerted by the prolapsing leaflets and mitral annular disjunction, to the inflammation's impact on fibrosis pathways along with a constitutional hyperadrenergic state. The heterogeneity of clinical course reveals a necessity of risk stratification, preferably through noninvasive multimodality imaging, that will help to identify and prevent adverse scenarios in young MVP patients.

The Global Burden of Valvular Heart Disease: From Clinical Epidemiology to Management.

Valvular heart disease is a leading cause of cardiovascular morbidity and mortality and a major contributor of symptoms and functional disability. Knowledge of valvular heart disease epidemiology and a deep comprehension of the geographical and temporal trends are crucial for clinical advances and the formulation of effective health policy for primary and secondary prevention. This review mainly focuses on the epidemiology of primary (organic, related to the valve itself) valvular disease and its management, especially emphasizing the importance of heart valve centers in ensuring the best care of patients through a multidisciplinary team.

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.

Stress Echocardiography in Italian Echocardiographic Laboratories: A Survey of the Italian Society of Echocardiography and Cardiovascular Imaging.

Background: The Italian Society of Echography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand the volumes of activity, modalities and stressors used during stress echocardiography (SE) in Italy. Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved through an electronic survey based on a structured questionnaire, uploaded on the SIECVI website. Results: Data were obtained from 228 echocardiographic laboratories, and SE examinations were performed in 179 centers (80.6%): 87 centers (47.5%) were in the northern regions of Italy, 33 centers (18.4%) were in the central regions, and 61 (34.1%) in the southern regions. We annotated a total of 4057 SE. We divided the SE centers into three groups, according to the numbers of SE performed: <10 SE (low-volume activity, 40 centers), between 10 and 39 SE (moderate volume activity, 102 centers) and ≥40 SE (high volume activity, 37 centers). Dipyridamole was used in 139 centers (77.6%); exercise in 120 centers (67.0%); dobutamine in 153 centers (85.4%); pacing in 37 centers (21.1%); and adenosine in 7 centers (4.0%). We found a significant difference between the stressors used and volume of activity of the centers, with a progressive increase in the prevalence of number of stressors from low to high volume activity (P = 0.033). The traditional evaluation of regional wall motion of the left ventricle was performed in all centers, with combined assessment of coronary flow velocity reserve (CFVR) in 90 centers (50.3%): there was a significant difference in the centers with different volume of SE activity: the incidence of analysis of CFVR was significantly higher in high volume centers compared to low - moderate - volume (32.5%, 41.0% and 73.0%, respectively, P < 0.001). The lung ultrasound (LUS) was assessed in 67 centers (37.4%). Furthermore for LUS, we found a significant difference in the centers with different volume of SE activity: significantly higher in high volume centers compared to low - moderate - volume (25.0%, 35.3% and 56.8%, respectively, P < 0.001). Conclusions: This nationwide survey demonstrated that SE was significantly widespread and practiced throughout Italy. In addition to the traditional indication to coronary artery disease based on regional wall motion analysis, other indications are emerging with an increase in the use of LUS and CFVR, especially in high-volume centers.

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.