Effects of sacubitril/valsartan on exercise capacity: a prognostic improvement that starts during uptitration.

PURPOSE: Sacubitril/valsartan is a mainstay of the treatment of heart failure with reduced ejection fraction (HFrEF); however, its effects on exercise performance yielded conflicting results. Aim of our study was to evaluate the impact of sacubitril/valsartan on exercise parameters and echocardiographic and biomarker changes at different drug doses. METHODS: We prospectively enrolled consecutive HFrEF outpatients eligible to start sacubitril/valsartan. Patients underwent clinical assessment, cardiopulmonary exercise test (CPET), blood sampling, echocardiography, and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Sacubitril/valsartan was introduced at 24/26 mg b.i.d. dose and progressively uptitrated in a standard monthly-based fashion to 97/103 mg b.i.d. or maximum tolerated dose. Study procedures were repeated at each titration visit and 6 months after reaching the maximum tolerated dose. RESULTS: Ninety-six patients completed the study, 73 (75%) reached maximum sacubitril/valsartan dose. We observed a significant improvement in functional capacity across all study steps: oxygen intake increased, at peak exercise (from 15.6 ± 4.5 to 16.5 ± 4.9 mL/min/kg; p trend = 0.001), while minute ventilation/carbon dioxide production relationship reduced in patients with an abnormal value at baseline. Sacubitril/valsartan induced positive left ventricle reverse remodeling (EF from 31 ± 5 to 37 ± 8%; p trend < 0.001), while NT-proBNP reduced from 1179 [610-2757] to 780 [372-1344] pg/ml (p trend < 0.0001). NYHA functional class and the subjective perception of limitation in daily life at KCCQ-12 significantly improved. The Metabolic Exercise Cardiac Kidney Index (MECKI) score progressively improved from 4.35 [2.42-7.71] to 2.35% [1.24-4.96], p = 0.003. CONCLUSIONS: A holistic and progressive HF improvement was observed with sacubitril/valsartan in parallel with quality of life. Likewise, a prognostic enhancement was observed.

Computed tomography predictors of structural valve degeneration in patients undergoing transcatheter aortic valve implantation with balloon-expandable prostheses.

OBJECTIVES: Computed tomography (CT) provides excellent anatomy assessment of the aortic annulus (AoA) and is utilized for pre-procedural planning of transcatheter aortic valve implantation (TAVI). We sought to investigate if geometrical characteristics of the AoA determined by CT may represent predictors of structural valve degeneration (SVD) in patients undergoing TAVI with balloon-expandable valves. METHODS: This is a retrospective study on 124 consecutive patients (mean age: 79 ± 7 years; female: 61%) undergoing balloon-expandable TAVI prospectively enrolled in a registry. AoA maximum diameter (Dmax), minimum diameter (Dmin), and area were assessed using pre-procedural CT. SVD was identified during follow-up with transthoracic echocardiography documenting structural prosthetic valve abnormalities with or without hemodynamic changes. RESULTS: The mean follow-up was 5.9 ± 1.7 years. SVD was found in 48 out of 124 patients (38%). AoA Dmax, Dmin, and area were significantly smaller in patients with SVD compared to patients without SVD (25.6 ± 2.2 mm vs. 27.1 ± 2.8 mm, p = 0.012; 20.5 ± 2.1 mm vs. 21.8 ± 2.1 mm, p = 0.001 and 419 ± 77 mm2 vs. 467 ± 88 mm2, p = 0.002, respectively). At univariable analysis, female sex, BSA, 23-mm prosthetic valve size, Dmax < 27.1 mm, and a Dmin < 19.9 mm were associated with SVD, whereas at multivariable analysis, only Dmin < 19.9 mm (OR = 2.873, 95% CI: 1.191-6.929, p = 0.019) and female sex (OR = 2.659, 95% CI: 1.095-6.458, p = 0.031) were independent predictors of SVD. CONCLUSIONS: Female sex and AoA Dmin < 19.9 mm are associated with SVD in patients undergoing TAVI with balloon-expandable valves. When implanting large prostheses in order to avoid paraprosthetic regurgitation, caution should be observed due to the risk of excessive stretching of the AoA Dmin, which may play a role in SVD. KEY POINTS: • Long-term durability is a concern for transcatheter aortic valve bioprosthesis. • CT provides an excellent assessment of the aortic annulus's geometrical characteristics for prosthesis sizing before transcatheter aortic valve implantation (TAVI). • Female sex and a small minimum aortic annulus diameter measured with CT are independent predictors of structural valve degeneration in patients undergoing TAVI with balloon-expandable valves.

A case of myopericarditis recurrence after third dose of BNT162b2 vaccine against SARS-CoV-2 in a young subject: link or causality?

The rate of post-vaccine myocarditis is being studied from the beginning of the massive vaccination campaign against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a direct cause-effect relationship has been described, in most cases, the vaccine pathophysiological role is doubtful. Moreover, it is not quite as clear as having had a previous myocarditis could be a risk factor for a post-vaccine disease relapse. A 27-year-old man presented to the emergency department for palpitations and pericardial chest pain radiated to the upper left limb, on the 4th day after the third dose of BNT162b2 vaccine. He experienced a previous myocarditis 3 years before, with full recovery and no other comorbidities. Electrocardiogram showed normal atrioventricular conduction, incomplete right bundle branch block, and diffuse ST-segment elevation. A cardiac echo showed lateral wall hypokinesis with preserved ejection fraction. Troponin-T was elevated (160 ng/L), chest X-ray was normal, and the SARS-CoV-2 molecular buffer was negative. High-dose anti-inflammatory therapy with ibuprofen and colchicine was started; in the 3rd day high-sensitivity Troponin I reached a peak of 23000 ng/L. No heart failure or arrhythmias were observed. A cardiac magnetic resonance was performed showing normal biventricular systolic function and abnormal tissue characterization suggestive for acute non-ischaemic myocardial injury (increased native T1 and T2 values, increased signal intensity at T2-weighted images and late gadolinium enhancement, all findings with matched subepicardial distribution) at the level of mid to apical septal, anterior, and anterolateral walls. A left ventricular electroanatomic voltage mapping was negative (both unipolar and bipolar), while the endomyocardial biopsy showed a picture consistent with active myocarditis. The patient was discharged in good clinical condition, on bisoprolol 1.25 mg, ramipril 2.5 mg, ibuprofen 600 mg three times a day, colchicine 0.5 mg twice a day. We presented the case of a young man with history of previous myocarditis, admitted with a non-complicated acute myopericarditis relapse occurred 4 days after SARS-CoV-2 vaccination (3rd dose). Despite the observed very low incidence of cardiac complications following BNT162b2 administration, and the lack of a clear proof of a direct cause-effect relationship, we think that in our patient this link can be more than likely. In the probable need for additional SARS-CoV-2 vaccine doses in the next future, studies addressing the risk-benefit balance of this subset of patient are warranted. We described a multidisciplinary management of a case of myocarditis recurrence after the third dose of SARS-CoV-2 BNT162b2 vaccine.

Non-stenotic fibro-calcific aortic valve as a predictor of myocardial infarction recurrence.

BACKGROUND: Patients with acute myocardial infarction (AMI) are at increased risk of recurrent cardiovascular events. Non-stenotic aortic valve fibro-calcific remodeling (AVSc), reflecting systemic damage, may serve as a new marker of risk. OBJECTIVES: To stratify subgroups of AMI patients with specific probabilities of recurrent AMI and to evaluate the importance of AVSc in this setting. METHODS: Consecutive AMI patients (n = 2530) were admitted at Centro Cardiologico Monzino (2010-2019) and followed up for 5 years. Patients were divided into study (n = 1070) and test (n = 966) cohorts. Topological data analysis (TDA) was used to stratify patient subgroups, while Kaplan-Meier and Cox regressions analyses were used to evaluate the significance of baseline characteristics. RESULTS: TDA identified 11 subgroups of AMI patients with specific baseline characteristics. Two subgroups showed the highest rate of reinfarction after 5 years from the indexed AMI with a combined hazard ratio (HR) of 3.8 (95%CI: 2.7-5.4) compared to the other subgroups. This was confirmed in the test cohort (HR = 3.1; 95%CI: 2.2-4.3). These two subgroups were mostly men, with hypertension and dyslipidemia, who exhibit higher prevalence of AVSc, higher levels of high-sensitive c-reactive protein and creatinine. In the year-by-year analysis, AVSc, adjusted for all confounders, showed an independent association with the increased risk of reinfarction (odds ratio of ∼2 at all time-points), in both the study and the test cohorts (all p < 0.01). CONCLUSIONS: AVSc is a crucial variable for identifying AMI patients at high risk of recurrent AMI and its presence should be considered when assessing the management of AMI patients. The inclusion of AVSc in risk stratification models may improve the accuracy of predicting the likelihood of recurrent AMI, leading to more personalized treatment decisions.

We wanted to understand the factors that make some acute myocardial infarction (AMI) patients more likely to experience recurrent infarction after leaving the hospital. Specifically, we asked whether a heart valve condition called non-stenotic aortic valve fibro-calcific remodeling (AVSc) could be a crucial factor. Our study used advanced data analysis techniques, including topological data analysis (TDA), to explore this question. We unveil that AVSc is indeed a significant predictor of recurrent infarction in AMI patients. Our findings suggest that the presence of aortic valve remodeling should be taken into account when assessing the risk of recurrent AMI and managing these patients.

Structural and functional abnormalities of left-sided cardiac chambers in Barlow's disease without significant mitral regurgitation.

AIMS: To explore the presence of left ventricular (LV) and left atrial (LA) morphological and functional abnormalities in patients with Barlow's disease (BD) without significant mitral regurgitation (MR) and to investigate whether these abnormalities may predict MR progression. METHODS AND RESULTS: Consecutive patients with BD were retrospectively identified from two tertiary centers; those with MR graded from trivial to mild-to-moderate were selected and matched with healthy controls in a 1:1 ratio. Conventional and speckle-tracking echocardiographic data were collected. The development of moderate-to-severe or greater MR was evaluated on follow-up echocardiograms.Patients with BD (n=231) showed increased LV dimensions and indexed LV mass (LVMi) in comparison to controls (p<0.001); LV remodeling worsened with higher MR severity and was accompanied by an increased prevalence of eccentric LV hypertrophy (eLVH). Moreover, BD patients had larger LA volumes and more impaired LA reservoir strain versus controls (p<0.001), while LV strain was similar between the two groups. Multivariable linear regression analyses in the overall population identified BD and MR grade as independent predictors of remodeling markers (LV dimensions, LVMi and LA volume), and BD as independent correlate of LA strain.MR progression was observed in 51 BD subjects (out of 170 patients with available follow-up). On Cox regression analysis, age, eLVH, mild-to-moderate MR and mitral annular disjunction (MAD) emerged as independent predictors of MR progression. CONCLUSIONS: BD patients without significant MR show early LV and LA remodeling, together with reduced LA strain. MR progression was associated with eccentric LV remodeling, MAD, and MR severity.

Rationale and design of the SPREAD study: Sport Practice and its Effects on Aortic Size and Valve Function in Bicuspid Aortic Valve Disease.

The bicuspid aortic valve (BAV) is the most common congenital heart defect among adults, often leading to severe valve dysfunction and aortic complications. Despite its clinical significance, uncertainties persist regarding the impact of sports participation on the natural course of BAV disease. The SPREAD (Sport PRactice and its Effects on Bicuspid Aortic valve Disease) study is a multicenter and multinational project designed to investigate this relationship. This paper outlines the study's design, and objectives. The study is divided into two phases; phase one involves a cross-sectional analysis comparing aortic dimensions and valve function among competitive athletes with BAV, athletes with tricuspid aortic valves (TAV), and sedentary individuals with BAV. The second phase is a prospective, longitudinal follow-up aiming to evaluate the impact of regular sports training on disease progression. The SPREAD study seeks to provide evidence-based insights into the effects of sports participation on BAV disease progression, guiding clinical decision-making regarding sports eligibility and risk stratification for individuals with BAV.

STress computed tomogRaphy perfusion and stress cArdiac magnetic resonance for ThE manaGement of suspected or known coronarY artery disease: resources and outcomes impact.

BACKGROUND: The aim of this study is to describe resources and outcomes of coronary computed tomography angiography plus Stress CT perfusion (CCTA â€‹+ â€‹Stress-CTP) and stress cardiovascular magnetic resonance (Stress-CMR) in symptomatic patients with suspected or known CAD. METHODS: Six hundred and twenty-four consecutive symptomatic patients with intermediate to high-risk pretest likelihood for CAD or previous history of revascularization referred to our hospital for clinically indicated CCTA â€‹+ â€‹Stress-CTP or Stress-CMR were enrolled. Stress-CTP scans were performed in 223 patients while 401 patients performed Stress-CMR. Patient follow-up was performed at 1 year after index test performance. Endpoints were all cardiac events, as a combined endpoint of revascularization, non-fatal MI and death, and hard cardiac events, as combined endpoint of non-fatal MI and death. RESULTS: Twenty-nine percent of patients who underwent CCTA â€‹+ â€‹Stress-CTP received revascularization, 7% of subjects assessed with Stress-CMR were treated invasively, and a low number of non-fatal MI and death was observed with both strategies (hard events in 0.4% of patients that had CCTA â€‹+ â€‹Stress-CTP as index test, and in 3% of patients evaluated with Stress-CMR). According to the predefined endpoints, CCTA â€‹+ â€‹Stress-CTP group showed high rate of all cardiac events and low rate of hard cardiac events, respectively. The cumulative costs were 1970 â€‹± â€‹2506 Euro and 733 â€‹± â€‹1418 Euro for the CCTA â€‹+ â€‹Stress-CTP group and Stress-CMR group, respectively. CONCLUSIONS: The use of CCTA â€‹+ â€‹Stress-CTP strategy was associated with high referral to revascularization but with a favourable trend in terms of hard cardiac events and diagnostic yield in identifying individuals at lower risk of adverse events despite the presence of CAD.

DEep LearnIng-based QuaNtification of epicardial adipose tissue predicts MACE in patients undergoing stress CMR.

BACKGROUND AND AIMS: This study investigated the additional prognostic value of epicardial adipose tissue (EAT) volume for major adverse cardiovascular events (MACE) in patients undergoing stress cardiac magnetic resonance (CMR) imaging. METHODS: 730 consecutive patients [mean age: 63 ± 10 years; 616 men] who underwent stress CMR for known or suspected coronary artery disease were randomly divided into derivation (n = 365) and validation (n = 365) cohorts. MACE was defined as non-fatal myocardial infarction and cardiac deaths. A deep learning algorithm was developed and trained to quantify EAT volume from CMR. EAT volume was adjusted for height (EAT volume index). A composite CMR-based risk score by Cox analysis of the risk of MACE was created. RESULTS: In the derivation cohort, 32 patients (8.7 %) developed MACE during a follow-up of 2103 days. Left ventricular ejection fraction (LVEF) < 35 % (HR 4.407 [95 % CI 1.903-10.202]; p<0.001), stress perfusion defect (HR 3.550 [95 % CI 1.765-7.138]; p<0.001), late gadolinium enhancement (LGE) (HR 4.428 [95%CI 1.822-10.759]; p = 0.001) and EAT volume index (HR 1.082 [95 % CI 1.045-1.120]; p<0.001) were independent predictors of MACE. In a multivariate Cox regression analysis, adding EAT volume index to a composite risk score including LVEF, stress perfusion defect and LGE provided additional value in MACE prediction, with a net reclassification improvement of 0.683 (95%CI, 0.336-1.03; p<0.001). The combined evaluation of risk score and EAT volume index showed a higher Harrel C statistic as compared to risk score (0.85 vs. 0.76; p<0.001) and EAT volume index alone (0.85 vs.0.74; p<0.001). These findings were confirmed in the validation cohort. CONCLUSIONS: In patients with clinically indicated stress CMR, fully automated EAT volume measured by deep learning can provide additional prognostic information on top of standard clinical and imaging parameters.

Is There a Typical Doppler Pattern in Patients With Apical Hypertrophic Cardiomyopathy With Aneurysm?

Nineteen consecutive patients with apical hypertrophic cardiomyopathy and apical aneurysm underwent a comprehensive echo-Doppler including continuous wave Doppler at midventricular level. Three different flow patterns, pattern A (more frequent), pattern B, and pattern C, and expression of different intracavitary pressure gradients were defined. (Level of Difficulty: Intermediate.).

Dramatic disease regression in a case of HFrEF with end-stage renal failure treated with sacubitril/valsartan and SGLT2i.

The amount of evidence for guideline-directed new heart failure (HFrEF) disease-modifying drugs in the context of chronic kidney disease (CKD) is relatively modest, especially in end-stage CKD. We report a case of dramatic reverse remodelling and disease regression in a naïve HFrEF young woman on haemodialysis treated with sacubitril/valsartan and SGLT2i. At 10-month follow-up, the patient normalized left ventricle and atrial volumes and improved ejection fraction to the normal range, assessed both by echocardiography and cardiac magnetic resonance. Cardiac biomarkers and exercise performance improved consensually. The haemodialysis protocol and the loop diuretic dose were unchanged within the whole period.

Endovascular Low-Pass Filter: Performing Mitral Edge-to-Edge Repair With PASCAL Through an Inferior Vena Cava Filter.

We present the case of an 82-year-old man with a history of inferior vena cava filter implantation and concomitant severe mitral regurgitation requiring transcatheter edge-to-edge repair. Despite being deemed ineligible for transfemoral access as technically challenging, he successfully underwent mitral transcatheter edge-to-edge repair after crossing and dilatation of the inferior vena cava filter. (Level of Difficulty: Intermediate.).

Echocardiography vs. CMR in the Quantification of Chronic Mitral Regurgitation: A Happy Marriage or Stormy Divorce?

Quantification of chronic mitral regurgitation (MR) is essential to guide patients' clinical management and define the need and appropriate timing for mitral valve surgery. Echocardiography represents the first-line imaging modality to assess MR and requires an integrative approach based on qualitative, semiquantitative, and quantitative parameters. Of note, quantitative parameters, such as the echocardiographic effective regurgitant orifice area, regurgitant volume (RegV), and regurgitant fraction (RegF), are considered the most reliable indicators of MR severity. In contrast, cardiac magnetic resonance (CMR) has demonstrated high accuracy and good reproducibility in quantifying MR, especially in cases with secondary MR; nonholosystolic, eccentric, and multiple jets; or noncircular regurgitant orifices, where quantification with echocardiography is an issue. No gold standard for MR quantification by noninvasive cardiac imaging has been defined so far. Only a moderate agreement has been shown between echocardiography, either with transthoracic or transesophageal approaches, and CMR in MR quantification, as supported by numerous comparative studies. A higher agreement is evidenced when echocardiographic 3D techniques are used. CMR is superior to echocardiography in the calculation of the RegV, RegF, and ventricular volumes and can provide myocardial tissue characterization. However, echocardiography remains fundamental in the pre-operative anatomical evaluation of the mitral valve and of the subvalvular apparatus. The aim of this review is to explore the accuracy of MR quantification provided by echocardiography and CMR in a head-to-head comparison between the two techniques, with insight into the technical aspects of each imaging modality.

Outcomes of Transcatheter Aortic Valve Replacement Patients With Different Transvalvular Flow-Gradient Patterns.

Low-flow low-gradient (LF-LG) aortic stenosis (AS) may occur with preserved or depressed left ventricular ejection fraction (LVEF). Both situations represent the most challenging subset of patients to manage and generally have a poor prognosis. Few and controversial data exist on the outcomes of these patients compared with normal flow-high gradient (NF-HG) AS after transcatheter aortic valve replacement (TAVR). We sought to characterize different transvalvular flow-gradient patterns and to examine their prognostic value after TAVR. We enrolled 1,208 patients with severe AS and categorized as follow: 976 patients NF-HG (mean aortic pressure gradient [MPG] ≥40 mm Hg), 107 paradoxical LF-LG (pLF-LG, MPG <40 mm Hg, LVEF ≥50%, stroke volume index <35 ml/m2), and 125 classical LF-LG (cLF-LG) (MPG <40 mm Hg, LVEF <50%, stroke volume index <35 ml/m2). When compared with NF-HG and pLF-LG, cLF-LG had a worse symptomatic status (New York Heart Association III to IV 86% vs 62% and 67%, p <0.001), a higher prevalence of eccentric hypertrophy and a higher level of LV global afterload reflected by a higher valvuloarterial impedance. Valvular function after TAVR was excellent over time in all patients. While 30-day mortality (p = 0.911) did not differ significantly among groups, cLF-LG had a lower 5-year survival rate (LF-LG 50% vs pLF-LG 62% and NF-HG 68%, p <0.05). cLF-LG was associated with a hazard ratio for mortality of 2.41 (95% confidence interval 1.65 to 3.52, p <0.001). In conclusion, TAVR is an effective procedure regardless of transvalvular flow-gradient patterns. However, special care should be given to characterized hemodynamic of AS, as patients with pLF-LG had similar survival rates than patients with NF-HG, whereas cLF-LG is associated with a twofold increased risk of mortality at 5-year follow-up.

Approach to the Patient with Acute Aortic Syndromes in Light of the New Consensus Statement on Multimodality Imaging in Thoracic Aortic Diseases.

Acute aortic syndromes comprise a range of interrelated conditions including aortic dissection, intramural hematoma, penetrating atherosclerotic ulcer, and contained or not contained aortic aneurysm rupture. These syndromes are potentially life threatening; therefore, a rapid and accurate diagnosis is crucial. A new Clinical Consensus Statement on Aortic and Peripheral Vascular Disease has recently been published, and we will try to highlight the main innovations in the document.

Quantification of extracellular volume with cardiac computed tomography in patients with dilated cardiomyopathy.

BACKGROUND: Cardiac computed tomography (CCT) was recently validated to measure extracellular volume (ECV) in the setting of cardiac amyloidosis, showing good agreement with cardiovascular magnetic resonance (CMR). However, no evidence is available with a whole-heart single source, single energy CT scanner in the clinical context of newly diagnosed left ventricular dysfunction. Therefore, the aim of this study was to test the diagnostic accuracy of ECVCCT in patients with a recent diagnosis of dilated cardiomyopathy, having ECVCMR as the reference technique. METHODS: 39 consecutive patients with newly diagnosed dilated cardiomyopathy (LVEF <50%) scheduled for clinically indicated CMR were prospectively enrolled. Myocardial segment evaluability assessment with each technique, agreement between ECVCMR and ECVCCT, regression analysis, Bland-Altman analysis and interclass correlation coefficient (ICC) were performed. RESULTS: Mean age of enrolled patients was 62 â€‹± â€‹11 years, and mean LVEF at CMR was 35.4 â€‹± â€‹10.7%. Overall radiation exposure for ECV estimation was 2.1 â€‹± â€‹1.1 â€‹mSv. Out of 624 myocardial segments available for analysis, 624 (100%) segments were assessable by CCT while 608 (97.4%) were evaluable at CMR. ECVCCT demonstrated slightly lower values compared to ECVCMR (all segments, 31.8 â€‹± â€‹6.5% vs 33.9 â€‹± â€‹8.0%, p â€‹< â€‹0.001). At regression analysis, strong correlations were described (all segments, r â€‹= â€‹0.819, 95% CI: 0.791 to 0.844). On Bland-Altman analysis, bias between ECVCMR and ECVCCT for global analysis was 2.1 (95% CI: -6.8 to 11.1). ICC analysis showed both high intra-observer and inter-observer agreement for ECVCCT calculation (0.986, 95%CI: 0.983 to 0.988 and 0.966, 95%CI: 0.960 to 0.971, respectively). CONCLUSIONS: ECV estimation with a whole-heart single source, single energy CT scanner is feasible and accurate. Integration of ECV measurement in a comprehensive CCT evaluation of patients with newly diagnosed dilated cardiomyopathy can be performed with a small increase in overall radiation exposure.

3D echocardiography in mitral valve prolapse.

Mitral valve prolapse (MVP) is the leading cause of mitral valve surgery. Echocardiography is the principal imaging modality used to diagnose MVP, assess the mitral valve morphology and mitral annulus dynamics, and quantify mitral regurgitation. Three-dimensional (3D) echocardiographic (3DE) imaging represents a consistent innovation in cardiovascular ultrasound in the last decades, and it has been implemented in routine clinical practice for the evaluation of mitral valve diseases. The focus of this review is the role and the advantages of 3DE in the comprehensive evaluation of MVP, intraoperative and intraprocedural monitoring.

Comparison between Automatic and Semiautomatic System for the 3D Echocardiographic Multiparametric Evaluation of RV Function and Dimension.

BACKGROUND: The right ventricle (RV) plays a pivotal role in cardiovascular diseases and 3-dimensional echocardiography (3DE) has gained acceptance for the evaluation of RV volumes and function. Recently, a new artificial intelligence (AI)-based automated 3DE software for RV evaluation has been proposed and validated against cardiac magnetic resonance. The aims of this study were three-fold: (i) feasibility of the AI-based 3DE RV quantification, (ii) comparison with the semi-automatic 3DE method and (iii) assessment of 2-dimensional echocardiography (2DE) and strain measurements obtained automatically. METHODS: A total of 203 subject (122 normal and 81 patients) underwent a 2DE and both the semi-automatic and automatic 3DE methods for Doppler standard, RV volumes and ejection fraction (RVEF) measurements. RESULTS: The automatic 3DE method was highly feasible, faster than 2DE and semi-automatic 3DE and data obtained were comparable with traditional measurements. Both in normal subjects and patients, the RVEF was similar to the two 3DE methods and 2DE and strain measurements obtained by the automated system correlated very well with the standard 2DE and strain ones. CONCLUSIONS: results showed that rapid analysis and excellent reproducibility of AI-based 3DE RV analysis supported the routine adoption of this automated method in the daily clinical workflow.

Prognostic Impact of Extra-Mitral Valve Cardiac Involvement in Patients With Primary Mitral Regurgitation.

BACKGROUND: In patients with severe primary mitral regurgitation (MR), the indication for surgery is currently based on the presence of symptoms, left ventricular dilatation and dysfunction, atrial fibrillation, and pulmonary hypertension. OBJECTIVES: The aim of this study was to evaluate the prognostic impact of the presence of extra-mitral valve cardiac involvement (including known risk factors but also severe left atrial [LA] dilatation and right ventricular [RV] dysfunction) in a large multicenter study of patients with primary MR. METHODS: Patients with severe primary MR undergoing surgery were included and categorized according to the extent (highest) of cardiac involvement: group 0, no cardiac involvement; group 1, left ventricular involvement; group 2, LA involvement; group 3, pulmonary vasculature or tricuspid valve involvement; or group 4, RV involvement. The outcome was all-cause mortality. RESULTS: A total of 1,106 patients were included (mean age 63 ± 12 years, 68% male). In total, 377 patients (34%) were classified in group 0, 239 (22%) in group 1, 213 (19%) in group 2, 180 (16%) in group 3, and 97 (9%) in group 4. Kaplan-Meier curve analysis revealed significantly worse survival (log-rank chi-square = 43.4; P < 0.001) with higher group. On multivariable analysis, age, male sex, chronic obstructive pulmonary disease, kidney function, and group of cardiac involvement were independently associated with all-cause mortality. For each increase in group, a 17% higher risk for all-cause mortality was observed (95% CI: 1.051-1.313; P = 0.005) during a median follow-up time of 88 months. CONCLUSIONS: In patients with severe primary MR, a novel classification system based on extra-mitral valve cardiac involvement may help refine risk stratification and timing of surgery, particularly including severe LA dilatation and RV dysfunction in the assessment.

Impact of Sacubitril/Valsartan on surfactant binding proteins, central sleep apneas, lung function tests and heart failure biomarkers: Hemodynamic or pleiotropism?

Purpose: Little is known about the mechanism underlying Sacubitril/Valsartan effects in patients with heart failure (HFrEF). Aim of the study is to assess hemodynamic vs. non-hemodynamic Sacubitril/Valsartan effects by analyzing several biological and functional parameters. Methods: Seventy-nine patients (86% males, age 66 ± 10 years) were enrolled. At baseline and 6 months after reaching the maximum Sacubitril/Valsartan tolerated dose, we assessed biomarkers, transthoracic echocardiography, polysomnography, spirometry, and carbon monoxide diffusing capacity of the lung (DLCO). Results: Mean follow-up was 8.7 ± 1.4 months with 83% of patients reaching Sacubitril/Valsartan maximum dose (97/103 mg b.i.d). Significant improvements were observed in cardiac performance and biomarkers: left ventricular ejection fraction increased (31 ± 5 vs. 37 ± 9 %; p < 0.001), end-diastolic and end-systolic volumes decreased; NT-proBNP decreased (1,196 [IQR 648-2891] vs. 958 [IQR 424-1,663] pg/ml; p < 0.001) in parallel with interleukin ST-2 (28.4 [IQR 19.4-36.6] vs. 20.4 [IQR 15.1-29.2] ng/ml; p < 0.001) and circulating surfactant binding proteins (proSP-B: 58.43 [IQR 40.42-84.23] vs. 50.36 [IQR 37.16-69.54] AU; p = 0.014 and SP-D: 102.17 [IQR 62.85-175.34] vs. 77.64 [IQR 53.55-144.70] AU; p < 0.001). Forced expiratory volume in 1 second and forced vital capacity improved. DLCO increased in the patients' subgroup (n = 39) with impaired baseline values (from 65.3 ± 10.8 to 70.3 ± 15.9 %predicted; p = 0.013). We also observed a significant reduction in central sleep apneas (CSA). Conclusion: Sacubitril/Valsartan effects share a double pathway: hemodynamic and systemic. The first is evidenced by NT-proBNP, proSP-B, lung mechanics, and CSA improvement. The latter is confirmed by an amelioration of DLCO, ST-2, SP-D as well as by reverse remodeling echocardiographic parameters.

The semantic of a pandemic: Are cardiovascular patients dying "with" or "from" COVID-19? Reflections from a case report.

RATIONALE: Northern Italy has been particularly hit by the current Covid-19 pandemic. Italian deceased patients have a mean age of 78.5 years and only 1.2% have no comorbidities. These data started a public debate whether patients die "with" or "from" Covid-19. If on one hand the public opinion has been persuaded to believe that Covid-19 infection has poor outcomes just in elderly and/or fragile subjects, on the other hand, hospitals are admitting an increasing number of healthy young patients needing semi-intensive or intensive care units. PATIENT CONCERNS: At the end of March 2020, a 79-year-old patient (M.G.) was admitted to the emergency department of our hospital with a 5 days history of fever, dyspnea, and cough. He was known for hypertension and coronary artery disease with a previous coronary artery stenting. Both the comorbidities were carried out without complications and the patient was previously asymptomatic and in good health. At admission, he was febrile and showed signs of respiratory failure with hypoxia and hypocapnia at blood gas analysis. DIAGNOSIS: The day after, he was tested for SARS-CoV-2 with a real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swab, which turned positive and a chest CT-Scan was consistent with the diagnosis of interstitial pneumonia. INTERVENTIONS: He was treated with i.v. diuretics, paracetamol, prolonged noninvasive ventilation (CPAP), and empiric antibiotic therapy on top of his chronic treatment. OUTCOMES: A treatment with heparin and corticosteroids was started; however, he developed irreversible respiratory failure. Invasive ventilation was not considered appropriate due to his comorbidities, low chances of recovery, and intensive care unit overcrowding. The patient died 9 days after admission. LESSONS: Health conditions that are most reported as risk factors are common cardiovascular diseases that can be managed in modern clinical practice. Through a brief illustrative clinical case, we would like to underline how Covid-19 can be per se the cause of death in patients that would otherwise have had an acceptable life expectancy.