Regional impairment of left ventricular longitudinal strain in aortic regurgitation.

BACKGROUND: Aortic regurgitation (AR) has an important impact on myocardial mechanics and recent studies have proved the value of global longitudinal strain (GLS) in the assessment of its severity and prognosis. Our purpose was to assess if the direct impact of the regurgitant jet on the myocardial wall could affect regional longitudinal strain. METHODS: Eighty patients with chronic moderate/severe AR were retrospectively studied. Patients were considered to have a jet-related longitudinal strain reduction when the myocardial segments directly impacted by the jet had their longitudinal strain reduced by at least 30% compared to nonaffected segments. AR severity, left ventricular (LV) size and function were compared according to the presence/absence of this regional pattern. For those who underwent surgery, postoperative regional and global LV function was also analyzed. RESULTS: A pattern of regional longitudinal strain impairment was identified in 43% of patients, with a regional reduction (in median) of 10 percentage points in absolute strain values in the segments impacted by the jet, compared to nonaffected segments. In the subgroup who underwent surgery, this pattern became attenuated after surgery. Patients with regional longitudinal strain impairment were less likely to improve GLS after surgery (10% vs. 38% improved GLS by at least 2.5%, P = 0.049). CONCLUSIONS: To our knowledge, this study identifies for the first time, a link between the location of the impact of the regurgitant jet in AR and regional longitudinal strain impairment. The presence of this regional pattern might be associated with worse postoperative LV recovery.

In vitro and in vivo evaluation of novel chromeno[2,3-d]pyrimidinones as therapeutic agents for triple negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the limited therapeutic options show poor efficacy in patients, associated to severe side effects and development of resistance. Considering that chromene-based scaffolds proved to be attractive candidates for cancer therapy, herein we prepared new chromeno[2,3-d]pyrimidinone derivatives by a simple two step procedure, starting from the reaction of cyanoacetamide and a salicylaldehyde. A cell viability screening in several breast cancer cell lines allowed to identify two promising compounds with IC50 values in the low micromolar range for TNBC cells. These chromenes inhibited cell proliferation, induced cell cycle arrest and triggered cell death through apoptosis. In vivo studies revealed a safe profile in invertebrate and vertebrate animal models and confirmed their capacity to inhibit tumor growth in the CAM model, inducing significant tumor regression after 4 days of treatment. The two compounds identified in this study are promising drug candidates for TNBC treatment and valuable hits for future optimization, using the versatile synthetic platform that was developed.

Repair of a gigantic ascending aortic pseudoaneurysm - A challenging approach.

Aortic pseudoaneurysms can be a potentially fatal, yet rare, complication of heart surgery. Surgery is indicated but is high risk during sternotomy. Therefore, careful planning is required. We report the case of a 57-year-old patient who underwent heart surgery twice in the past and who presented with an ascending aortic pseudoaneurysm. A successful repair of the pseudoaneurysm was performed under deep hypothermia, left ventricular apical venting, periods of circulatory arrest and endoaortic balloon occlusion.

LGE prevalence and patterns in severe aortic stenosis: When "junctional" means the same.

BACKGROUND: Left ventricular (LV) remodeling in severe aortic valve stenosis (AS) is a complex process that goes beyond hypertrophic response. Reparative/replacement fibrosis is considered irreversible and has recognized value in both risk stratification and prognosis. Currently, cardiac magnetic resonance (CMR) is the gold-standard imaging technique for fibrosis identification through late gadolinium enhancement (LGE) assessment. However, its prevalence and distribution are quite variable among series. Our goal was to assess LGE prevalence and patterns in severe AS. METHODOLOGY: Single-center prospective cohort of 140 patients with severe symptomatic high-gradient AS (mean age 72 ± 8 years; mean valvular transaortic gradient 61 ± 18 mmHg; mean LV ejection fraction by echocardiogram 58 ± 9%) undergoing surgical aortic valve replacement. Those with previous myocardial infarction and/or non-ischemic cardiomyopathy were excluded. All patients performed 1.5 T LGE-CMR prior to surgery. RESULTS: Overall, 103 patients (74%) had non-ischemic LGE (median LGE mass 2.8 g [IQR 0.0-7.8] g), many of them with combined mid-wall and junctional enhancement pattern (36%). LGE was most frequently observed in the mid-basal segments of the interventricular septum. Seventy-four patients (53%) had non-exclusively junctional LGE. Contrary to those with junctional enhancement, patients with non-exclusively junctional LGE had higher LV volumes/mass, worse LV ejection fraction and worse global longitudinal strain. CONCLUSION: Among patients with severe, symptomatic, high-gradient AS, LGE is frequent, primarily affecting the mid-basal interventricular septum. Contrary to junctional LGE, the presence of non-junctional LGE seems to correlate with adverse markers of LV remodeling.

Prevalence and significance of relative apical sparing in aortic stenosis: insights from an echo and cardiovascular magnetic resonance study of patients referred for surgical aortic valve replacement.

AIMS: This study aims to assess the prevalence of relative apical sparing pattern (RASP) in patients with severe symptomatic aortic stenosis (AS), referred for surgical aortic valve replacement (AVR), to evaluate its significance, possible relation to amyloid deposition, and persistence after surgery. METHODS AND RESULTS: Prospective study of 150 consecutive patients [age 73 (interquartile range: 68-77), 51% women], with severe symptomatic AS referred to surgical AVR. All patients underwent cardiac magnetic resonance (CMR) before surgery. RASP was defined by [average apical longitudinal strain (LS)/(average basal LS + average mid LS)] > 1 by echocardiography. AVR was performed in 119 (79.3%) patients. Both Congo red and sodium sulphate-Alcian blue (SAB) stain were used to exclude amyloid on septal myocardial biopsy. LV remodelling and tissue characterization parameters were compared in patients with and without RASP. Deformation pattern was re-assessed at 3-6 months after AVR.RASP was present in 23 patients (15.3%). There was no suspicion of amyloid at pre-operative CMR [native T1 value 1053 ms (1025-1076 ms); extracellular volume (ECV) 28% (25-30%)]. None of the patients had amyloid deposition at histopathology. Patients with RASP had significantly higher pre-operative LV mass and increased septal wall thickness. They also had higher N-terminal pro b-type natriuretic peptide (NT-proBNP) levels [1564 (766-3318) vs. 548 (221-1440) pg/mL, P = 0.010], lower LV ejection fraction (53.7 ± 10.5 vs. 60.5 ± 10.2%, P = 0.005), and higher absolute late gadolinium enhancement (LGE) mass [9.7 (5.4-14.1) vs. 4.8 (1.9-8.6) g, P = 0.016] at CMR. Follow-up evaluation after AVR revealed RASP disappearance in all except two of the patients. CONCLUSION: RASP is not specific of cardiac amyloidosis. It may also be found in severe symptomatic AS without amyloidosis, reflecting advanced LV disease, being mostly reversible after surgery.

Pectoralis major muscle quantification by cardiac MRI is a strong predictor of major events in HF.

Clinical overt cardiac cachexia is a late ominous sign in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The main goal of this study was to assess the feasibility and prognostic significance of muscle mass quantification by cardiac magnetic resonance (CMR) in HF with reduced LVEF. HF patients with LVEF < 40% (HFrEF) referred for CMR were retrospectively identified in a single center. Key exclusion criteria were primary muscle disease, known infiltrative myocardial disease and intracardiac devices. Pectoralis major muscles were measured on standard axial images at the level of the 3rd rib anteriorly. Time to all-cause death or HF hospitalization was the primary endpoint. A total of 298 HF patients were included (mean age 64 ± 12 years; 76% male; mean LVEF 30 ± 8%). During a median follow-up of 22 months (IQR: 12-33), 67 (22.5%) patients met the primary endpoint (33 died and 45 had at least 1 HF hospitalization). In multivariate analysis, LVEF [Hazard Ratio (HR): 0.950; 95% Confidence Interval (CI): 0.917-0.983; p = 0.003), NYHA class I-II vs III-IV (HR: 0.480; CI: 0.272-0.842; p = 0.010), creatinine (HR: 2.653; CI: 1.548-4.545; p < 0.001) and pectoralis major area (HR: 0.873; 95% CI: 0.821-0.929; p < 0.001) were independent predictors of the primary endpoint, when adjusted for gender and NT-pro-BNP levels. Pectoralis major size measured by CMR in HFrEF was independently associated with a higher risk of death or HF hospitalization. Further studies to establish appropriate age and gender-adjusted cut-offs of muscle areas are needed to identify high-risk subgroups.

Diagnostic accuracy of computed tomography angiography for the exclusion of coronary artery disease in candidates for transcatheter aortic valve implantation.

Coronary CT angiography (CTA) is currently considered a reliable method to exclude obstructive coronary artery disease (CAD) before valvular heart surgery in patients with low pretest probability. However, its role in excluding obstructive CAD before transcatheter aortic valve implantation (TAVI) is less well established. Single-center retrospective study where patients with severe symptomatic aortic stenosis underwent both CTA and invasive coronary angiography (ICA) as part of TAVI planning. CTA exams were conducted on a 64-slice dual source scanner, with a median interval of 45 days to ICA (IQR 25-75 [13-82]). In both tests, obstructive CAD was defined as a ≥50% stenosis in an epicardial vessel ≥2 mm diameter. Per-patient, per-vessel and per-proximal segment analyses were conducted, excluding and including non-evaluable segments. The study included 200 patients (120 women, mean age 83 ± 6 years). The prevalence of obstructive CAD on ICA was 35.5% (n = 71). On a per-patient analysis (assuming non-evaluable segments as stenotic), CTA showed sensitivity of 100% (95% CI, 95-100%), specificity of 42% (95% CI, 33-51%), and positive and negative predictive values of 48% (95% CI, 44-51%) and 100% (95% CI, 92-100%), respectively. CTA was able to exclude obstructive CAD in 54 patients (27%), in whom ICA could have been safely withheld. Despite the high rate of inconclusive tests, pre-procedural CTA is able to safely exclude obstructive CAD in a significant proportion of patients undergoing TAVI, possibly avoiding the need for ICA in roughly one quarter of the cases.

Long-term assessment of the Ross procedure in adults: Clinical and echocardiographic follow-up at 20 years.

INTRODUCTION: The Ross procedure is an alternative to standard aortic valve (AV) replacement in young and middle-aged patients. However, durability and incidence of reoperation remain a concern for most cardiac surgeons. Our aim was to assess very long-term clinical and echocardiographic outcomes of the Ross procedure. METHODS: We conducted a single-center retrospective analysis of 56 consecutive adult patients who underwent the Ross procedure. Mean age at surgery was 44±12 years (range, 16-65 years) and 55% were male. Clinical endpoints included overall mortality and the need for valve reoperation due to graft failure. The echocardiographic endpoint was the presence of any graft deterioration. Median clinical follow-up was 20 years (1120 patient/years). RESULTS: Indications for surgery were dominant aortic stenosis in 50% and isolated aortic regurgitation in 21%. Concomitant mitral valve repair was performed in 21% and a subcoronary technique was most commonly used (86%). Overall long-term survival was 91%, 80% and 77% at 15, 20 and 24 years, respectively. The survival rate was similar to the age- and gender-matched general population (p=0.44). During the follow-up period, freedom from graft reoperation was 80%. Eleven patients (31%) developed moderate AV regurgitation, three (8.6%) developed moderate pulmonary regurgitation and one (2.9%) presented moderate pulmonary stenosis. CONCLUSION: The Ross procedure, mostly using a subcoronary approach, proved to have good clinical and hemodynamic results, with low reoperation rates in long-term follow-up. Moderate autograft regurgitation was a frequent finding but had no significant clinical impact.

Behind Recurrent Thromboembolic Events.

We describe the case of a 68-year-old man, who presented with an ischemic stroke due to cardiac embolization related to mitral valve endocarditis. Blood cultures were always negative and post-operative valve histology did not show microorganisms. The patient also presented further recurrent peripheral embolic events. These clinical aspects were the first sign of a pancreas adenocarcinoma, which was only diagnosed in the clinical autopsy. In conclusion, these clinical findings of recurrent thromboembolic events with no microorganisms isolated suggests the diagnostic of a marantic endocarditis. LEARNING POINTS: Marantic endocarditis is characterized by the deposition of fibrin and thrombi on heart valves in the absence of microorganisms.Is associated with higher incidence of thromboembolic events and most commonly found in patients with neoplasia in post-mortem studies.It is a diagnostic challenge to distinguish from infective endocarditis and a high clinical suspicion is crucial to confirm the diagnosis.