MicroRNA-30d and -483-3p for bi-ventricular remodelling and miR-126-3p for pulmonary hypertension in advanced heart failure.

AIMS: MicroRNAs play a role in pathogenic mechanisms leading to heart failure. We measured a panel of 754 miRNAs in the myocardial tissue and in the serum of patients with heart failure with reduced ejection fraction due to dilatative idiopathic cardiomyopathy (DCM, N = 10) or ischaemic cardiomyopathy (N = 3), referred to left ventricular assist device implant. We aim to identify circulating miRNAs with high tissue co-expression, significantly associated to echocardiographic and haemodynamic measures. METHODS AND RESULTS: We have measured a panel of 754 miRNAs in the myocardial tissue [left ventricular (LV) apex] and in the serum obtained at the same time in a well selected study population of end-stage heart failure with reduced ejection fraction due to either DCM or ischaemic cardiomyopathy, referred to continuous flow left ventricular assist device implant. We observed moderate agreement for miR-30d, miR-126-3p, and miR-483-3p. MiR-30d was correlated to LV systolic as well as diastolic volumes (r = 0.78, P = 0.001 and r = 0.80, P = 0.005, respectively), while miR-126-3p was associated to mPAP and PCWP (r = -0.79, P = 0.007 and r = -0.80, P = 0.005, respectively). Finally, serum miR-483-3p had an association with right ventricular end diastolic diameter (r = -0.73, P = 0.02) and central venous pressure (CVP) (r - 0.68 p 0.03). CONCLUSIONS: In patients with DCM, few miRNAs are co-expressed in serum and tissue: They are related to LV remodelling (miR-30d), post-capillary pulmonary artery pressure (miR-126-3p), and right ventricular remodelling/filling pressures (miR-483-3p). Further studies are needed to confirm their role in diagnosis, prognosis or as therapeutic targets in heart failure with reduced ejection fraction.

Molecular Analysis With 16S rRNA PCR/Sanger Sequencing and Molecular Antibiogram Performed on DNA Extracted From Valve Improve Diagnosis and Targeted Therapy of Infective Endocarditis: A Prospective Study.

BACKGROUND: Molecular analysis (MA) on heart valve (HV) improves the microbiologic diagnosis of infectious endocarditis (IE). The main drawback of MA is the lack of antimicrobial susceptibility information. METHODS: We conducted a prospective cohort observational study of consecutive adult patients from April 2012 to May 2021 who underwent valve surgery at our hospital. The performance of MA, blood cultures (BC) and valve cultures (VC), and the diagnostic and therapeutic impact of MA were evaluated. Molecular antibiogram results were compared to culture-based antimicrobial susceptibility testing (AST). RESULTS: A total of 137 patients with definite IE and 52 patients with no IE were enrolled in the study. Among IE cases BC, VC, and MA were positive in 75 (55%), 30 (22%), and 120 (88%) of IE cases, respectively. Among 62 cases of BC-negative IE (BCNE), 57 achieved diagnosis with MA. MA led to a change of antimicrobial therapy in 92% of BCNE. MA was negative in 100% of patients with no IE. Molecular antibiogram performed on 17 valve specimens that resulted positive for pathogens potential carrier of genes encoding for multidrug resistant mechanisms showed 100% concordance with AST. CONCLUSIONS: MA showed a high specificity and sensitivity in etiological diagnosis of IE. Molecular antibiogram could overcome the major limitation of MA that is the lack of susceptibility testing. We advocate for the inclusion of MA among diagnostic criteria for IE and for a more extensive use of molecular antibiogram when the culture result is negative, and MA is the only positive test.

Septal Thickness Does Not Impact Outcome After Hypertrophic Obstructive Cardiomyopathy Surgery (Septal Myectomy and Subvalvular Mitral Apparatus Remodeling): A 15-Years of Experience.

Background: The aim of this study was to assess the impact of septal thickness on long-term outcomes of surgical treatment for hypertrophic obstructive cardiomyopathy (HOCM) and correction of mitral subvalvular anomalies. Methods: Sixty-six consecutive patients (58 ± 12 years, 56% female) undergoing extended septal myectomy and subvalvular mitral apparatus remodeling from 2007 to 2021 were retrospectively reviewed. Patients were divided into 2 groups according to septal thickness: moderate [< 18 mm, 29 patients (44%)] and severe [≥ 18 mm, 37 patients (56%)]. End points included survival, symptom improvement, reduction of left ventricle outflow tract (LVOT) gradient, resolution of mitral regurgitation (MR), and reoperation. Results: The mean interventricular septal thickness was 19 ± 3 mm, 15.8 ± 0.8 mm in patients with moderate and 21.4 ± 3.2 mm in those with severe hypertrophy. Preoperative data, intraoperative variables, postoperative complication rates, pre-discharge echocardiographic and clinical parameters did not differ between the two study groups [except for procedures involving the posterior mitral leaflet (p = 0.033) and septal thickness after myectomy (p = 0.0001)]. Subvalvular apparatus remodeling (secondary chordae of mitral valve resection and papillary muscle and muscularis trabecula procedures including resection, splitting, and elongation) was invariably added to septal myectomy (100%). Four (6%) procedures involved the posterior mitral leaflets. Mitral valve replacement was carried out in two patients (3%, p = 0.4). Reoperation for persistent MR was necessary in one patient (1%, p = 0.4). Neither iatrogenic ventricular septal defect nor in-hospital mortality occurred. During follow-up (mean 4.8 ± 3.8 years), two deaths occurred. NYHA class was reduced from 2.9 ± 0.7 to 1.6 ± 0.6 (p < 0.0001), the LVOT gradient from 89.7 ± 34.5 to 16.3 ± 8.8 mmHg (p < 0.0001), mitral valve regurgitation grade from 2.5 ± 1 to 1.2 ± 0.5 (p < 0.0001), and septal thickness from 18.9 ± 3.7 to 13.9 ± 2.7 mm (p < 0.0001). Conclusions: Regardless of septal thickness, subvalvular apparatus remodeling with concomitant septal myectomy can provide satisfactory long-term outcomes in terms of symptom improvement, LVOT obstruction relief, and MR resolution (without mitral valve replacement in most cases) in patients with HOCM.

Usefulness of regional right ventricular and right atrial strain for prediction of early and late right ventricular failure following a left ventricular assist device implant: A machine learning approach.

BACKGROUND: Identifying candidates for left ventricular assist device surgery at risk of right ventricular failure remains difficult. The aim was to identify the most accurate predictors of right ventricular failure among clinical, biological, and imaging markers, assessed by agreement of different supervised machine learning algorithms. METHODS: Seventy-four patients, referred to HeartWare left ventricular assist device since 2010 in two Italian centers, were recruited. Biomarkers, right ventricular standard, and strain echocardiography, as well as cath-lab measures, were compared among patients who did not develop right ventricular failure (N = 56), those with acute-right ventricular failure (N = 8, 11%) or chronic-right ventricular failure (N = 10, 14%). Logistic regression, penalized logistic regression, linear support vector machines, and naïve Bayes algorithms with leave-one-out validation were used to evaluate the efficiency of any combination of three collected variables in an "all-subsets" approach. RESULTS: Michigan risk score combined with central venous pressure assessed invasively and apical longitudinal systolic strain of the right ventricular-free wall were the most significant predictors of acute-right ventricular failure (maximum receiver operating characteristic-area under the curve = 0.95, 95% confidence interval = 0.91-1.00, by the naïve Bayes), while the right ventricular-free wall systolic strain of the middle segment, right atrial strain (QRS-synced), and tricuspid annular plane systolic excursion were the most significant predictors of Chronic-RVF (receiver operating characteristic-area under the curve = 0.97, 95% confidence interval = 0.91-1.00, according to naïve Bayes). CONCLUSION: Apical right ventricular strain as well as right atrial strain provides complementary information, both critical to predict acute-right ventricular failure and chronic-right ventricular failure, respectively.

Independent Effects of Hypertension and Obesity on Left Ventricular Mass and Geometry: Evidence from the Cardiovision 2030 Study.

Obesity and hypertension independently promote pathological left ventricular remodelling (LVR) and left ventricular hypertrophy (LVH), but to what extent they do so when they do not coexist is unclear. We used data from the Cardiovision Brno 2030 study to assess-for the first time in a region where no investigations have been previously carried out-the independent association of obesity and hypertension with LV geometry, and to evaluate the effects of hypertension in normal weight patients and the effects of obesity in normotensive patients. Overall, 433 individuals, aged 25⁻65 years, with no history of cardiovascular disease and/or antihypertensive treatment, were stratified into four groups according to BMI and hypertension: normal weight non-hypertensive (NWNH), normal weight hypertensive (NWH), overweight/obese non-hypertensive (ONH) and overweight/obese hypertensive (OH). LVR was classified as normal, concentric LVR (cLVR), concentric LVH (cLVH) or eccentric LVH (eLVH). Linear regression analysis demonstrated that body mass index (BMI) and systolic blood pressure (SBP) are the main predictors of LV mass and that they interact: SBP had a stronger effect in overweight/obese (ß = 0.195; p = 0.033) compared to normal weight patients (ß = 0.134; p = 0.048). Hypertension increased the odds of cLVR (OR = 1.78; 95%CI = 1.04⁻3.06; p = 0.037) and cLVH (OR = 8.20; 95% CI = 2.35⁻28.66; p = 0.001), independent of age, sex and BMI. Stratified analyses showed that NWH had a greater odd of cLVH (OR = 7.96; 95%CI = 1.70⁻37.08; p = 0.008) and cLVR (OR = 1.62; 95%CI = 1.02⁻3.34; p = 0.047) than NWNH. In the absence of hypertension, obesity was not associated with LVM and abnormal LV geometry, suggesting that it is not per se a determinant of LVR. Thus, antihypertensive therapy still remains the first-line approach against LVH in hypertensive patients, though weight loss interventions might be helpful in those who are obese.

Pathoanatomic Findings and Treatment During Hypertrophic Obstructive Cardiomyopathy Surgery: The Role of Mitral Valve.

BACKGROUND: To assess the role of the mitral valve apparatus (leaflets, chordae and papillary muscles, (PM)) in left ventricle outflow tract (LVOT) obstruction, and results of the surgical treatment for hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Twenty-eight consecutive patients (58±11years, 53% female) undergoing HOCM surgery from 2007 to 2016 at our institute were retrospectively reviewed. Endpoints included the involvement of the mitral valve in LVOT obstruction, mortality, and changes in clinical and echocardiographic characteristics after HOCM surgery. RESULTS: Secondary chordae tendineae tractioning the anterior mitral leaflet to the interventricular septum, and systolic anterior motion were detected in 78% of the patients. Anomalous, hypertrophied, and fused PM with muscularis trabeculae hypertrophy were found in 50%, 25%, and 35% of the patients, respectively. Four patients had posterior leaflet redundancy. Secondary chordae (92%), PM, and muscularis trabeculae resection (71%), and PM splitting and elongation (28%) were added variably to septal myectomy (100%). Nine procedures (32%) on mitral valve leaflets were performed, involving six posterior and three anterior mitral leaflets. Long-term follow-up was 4±2.8years. There was no hospital mortality, and NYHA was reduced from 3±0.5 to 1±0.7 (p<0.0001), the LVOT gradient from 88±35 to 20±18mmHg (p<0.0001), mitral valve regurgitation from grade 3±1 to 1±0.7 (p<0.0001), and septum thickness from 18±3 to 14±2mm (p<0.0001). CONCLUSIONS: The mitral valve apparatus contributes with all its components variably to LVOT dynamic obstruction thus surgical correction in addition to extended myectomy is recommended to achieve the best outcome.

Modeling Right Ventricle Failure After Continuous Flow Left Ventricular Assist Device: A Biventricular Finite-Element and Lumped-Parameter Analysis.

The risk of right ventricle (RV) failure remains a major contraindication for continuous-flow left ventricular assist device (CF-LVAD) implantation in patients with heart failure. It is therefore critical to identify the patients who will benefit from early intervention to avoid adverse outcomes. We sought to advance the computational modeling description of the mechanisms underlying RV failure in LVAD-supported patients. RV failure was studied by computational modeling of hemodynamic and cardiac mechanics using lumped-parameter and biventricular finite element (FE) analysis. Findings were validated by comparison of bi-dimensional speckle-tracking echocardiographic strain assessment of the RV free wall vs. patient-specific computational strain estimations, and by non-invasive lumped-based hemodynamic predictions vs. invasive right heart catheterization data. Correlation analysis revealed that lumped-derived RV cardiac output (R = 0.94) and RV stroke work index (R = 0.85) were in good agreement with catheterization data collected from 7 patients with CF-LVAD. Biventricular FE analysis showed abnormal motion of the interventricular septum towards the left ventricular free wall, suggesting impaired right heart mechanics. Good agreement between computationally predicted and echocardiographic measured longitudinal strains was found at basal (- 19.1 ± 3.0% for ECHO, and - 16.4 ± 3.2% for FEM), apical (- 20.0 ± 3.7% for ECHO, and - 17.4 ± 2.7% for FEM), and mid-level of the RV free wall (- 20.1 ± 5.9% for echo, and - 18.0 ± 5.4% for FEM). Simulation approach here presented could serve as a tool for less invasive and early diagnosis of the severity of RV failure in patients with LVAD, although future studies are needed to validate our findings against clinical outcomes.

Peripheral Artery Disease and Continuous Flow Left Ventricle Assist Device: An Engaging Complement Analysis May Help to Guide Treatment.

Use of continuous flow left ventricle assist device (CF-LVAD) in advanced heart failure (HF) patients results in clinically relevant improvements in survival, functional capacity, and quality of life. Peripheral artery disease (PAD) can occur in patients with CF-LVAD due to the high rate of concomitance between risk factors for atherosclerosis and HF. Diagnosis of PAD can be difficult in the specific setting of a patient supported by this kind of device because of the marked alteration in waveform morphology and velocity created by the artificial physiology of an LVAD. We report the case of a 53-year-old man with HF secondary to ischemic cardiomyopathy supported by the HeartWare HVAD as bridge to transplant, who after the implant developed symptoms suggestive of PAD. We describe additional computational flow analysis for the study of PAD-related hemodynamic disturbances induced by a CF-LVAD. Flow simulations enhance the information of clinical image data, and may have an application in clinical investigations of the risk of hemodynamic disturbances induced by LVAD implantation.

Shear stress alterations in the celiac trunk of patients with a continuous-flow left ventricular assist device as shown by in-silico and in-vitro flow analyses.

BACKGROUND: The use of left ventricular assist devices (LVADs) to treat advanced cardiac heart failure is constantly increasing, although this device leads to high risk for gastrointestinal bleeding. METHODS: Using in-silico flow analysis, we quantified hemodynamic alterations due to continuous-flow LVAD (HeartWare, Inc., Framingham, MA) in the celiac trunk and major branches of the abdominal aorta, and then explored the relationship between wall shear stress (WSS) and celiac trunk orientation. To assess outflow from the aortic branch, a 3-dimensional-printed patient-specific model of the celiac trunk reconstructed from an LVAD-supported patient was used to estimate echocardiographic outflow velocities under continuous-flow conditions, and then to calibrate computational simulations. Moreover, flow pattern and resulting WSS values were computed for 5 patients with LVAD implantation. RESULTS: Peak WSS values were estimated on the 3 branches of the celiac trunk and the LVAD cannula. The mean WSSs demonstrated that the left gastric artery underwent the highest WSS of 9.08 ± 5.45 Pa, with an average flow velocity of 0.57 ± 0.25 m/s compared with that of other vessel districts. The common hepatic artery had a less critical WSS of 4.58 ± 1.77 Pa. A positive correlation was found between the celiac trunk angulation and the WSS stress just distal to the ostium of the celiac trunk (R = 0.9), which may increase vulnerability of this vessel to bleeding. CONCLUSIONS: Although further studies are needed to confirm these findings in a larger patient cohort, computational flow simulations may enhance the information of clinical image data and may have an application in clinical investigations of hemodynamic changes in LVAD-supported patients.

From Small Coronary Artery Aneurysm to Giant Left Ventricle Aneurysm.

OBJECTIVE: To underscore how challenging the treatment of a coronary artery aneurysm (CAA) can be and highlight the need for consensus guidelines based on focused registries. CLINICAL PRESENTATION AND INTERVENTION: A 58-year-old man presented with acute coronary syndrome and underwent elective stent placement on a right CAA. The procedure was complicated by inferior acute myocardial infarction; 8 months later, due to remodeling toward a left ventricular aneurysm of the inferior wall, he experienced several episodes of sustained ventricular tachycardia that required urgent surgical treatment. CONCLUSION: The best therapeutic option for CAA is still a matter of controversy, and though the percutaneous approach can meet the technical challenges, 'heart team'-based decision-making is recommended. The case reported here showed that percutaneous treatment of CAA can be a challenging procedure, even in experienced and high-volume centers. In our patient's case, undersizing the covered stent led to further migration and to a complication that was more severe than the original disease.

Aortic surgery in Marfan patients with severe pectus excavatum.

AIMS: The optimal surgical management of the aortic root phenotype Marfan patients with severe pectus excavatum is a subject of debate. All the available literature were reviewed according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) principles in order to assess the early outcomes of both pectus excavatum and aortic repair techniques. METHODS: Searches were done in PubMed and MEDLINE electronic databases dating from July 1953 to December 2015. RESULTS: A total of 97 peer-reviewed publications were retrieved, and 27 relevant publications were identified with a total of 39 Marfan patients with pectus excavatum who underwent ascending aorta and aortic root surgery. Emergency acute Type-A aortic dissection repair was reported in five cases. Concomitant pectus excavatum and aortic root repair and composite graft implantation were the most commonly performed procedures. Complications after a staged or a combined approach were uncommon and no deaths occurred. CONCLUSION: Aortic surgery in Marfan patients with pectus excavatum was carried out according to a variety of strategies, surgical techniques and accesses with low complications rate and no mortality. Many of these were well tolerated with minimal complications and no mortality.

Heart transplant program at IRCCS-ISMETT: Impact of mechanical circulatory support on pre- and post -transplant survival.

BACKGROUND: Heart transplantation (HTx) improves the quality of life and survival in patients affected by end-stage heart failure. The purpose of the current study is to present the patients' clinical data and results of HTx in a single Center of Sicily. Focus on survival after pre and post HTx mechanical circulatory support use will be performed. METHODS: 133 HTx were done from 2004 to the end of 2015.The average donor age was 34±13.5years and the proportion of male donors was 67%. Percentage of use of mechanical circulatory support to bridge patients to HTx was 18%. RESULTS: Overall pre-transplant mechanical circulatory support was not correlated to worse post-transplant prognosis, p=0.757. Severe primary early graft failure requiring extra corporeal membrane oxygenator support strongly impact the early mortality after heart transplantation (p<0.001). CONCLUSIONS: The results of HTx at ISMETT are comparable to those reported in high volume Italian transplant centers as well as in the ISHLT registry. The favorable outcome can be related to focus on multidisciplinary approach, strict recipients' selection and young donor population. Post HTx mechanical circulatory support use in general remains associated with worse post-transplant outcomes. This does not apply to pre-op mechanical circulatory support population.

Dysfunction of mechanical mitral prosthesis at 33rd week of pregnancy: ECMO support as a complex strategy for the mother and the fetus.

Pregnant women with mechanical prosthetic heart valves have an increased risk of thrombosis and valve malfunctioning. Surgery carries a high risk of mortality for the mother and the fetus. A strategy for effective anticoagulation is crucial for these patients because both oral anticoagulants and heparin are associated with high risks for the mother and the fetus. The treatment of a pregnant woman with thrombosis and valve malfunction is a challenge, even for multidisciplinary teams, as cardiac surgery carries considerable risks. We present a woman at her 33rd week of pregnancy affected by congestive cardiac decompensation due to mechanical mitral prosthesis dysfunction. Given the expanded indication for ECMO and the recent evidence of the procedure's increased safety, even in the peri-partum period, we centered the treatment on VA-ECMO initiation before a Cesarean section (C-section) to guarantee support during surgery and avoid excessive anticoagulation or hypoperfusion to the fetus and as a bridge to cardiac surgery two days later. The strategy resulted in a good outcome with no complications for the mother and the fetus and a reasonable length of stay.

MicroRNA-30 mediates anti-inflammatory effects of shear stress and KLF2 via repression of angiopoietin 2.

MicroRNAs are endogenously expressed small noncoding RNAs that regulate gene expression. Laminar blood flow induces atheroprotective gene expression in endothelial cells (ECs) in part by upregulating the transcription factor KLF2. Here, we identified KLF2- and flow-responsive miRs that affect gene expression in ECs. Bioinformatic assessment of mRNA expression patterns identified the miR-30-5p seed sequence to be highly enriched in mRNAs that are downregulated by KLF2. Indeed, KLF2 overexpression and shear stress stimulation in vitro and in vivo increased the expression of miR-30-5p family members. Furthermore, we identified angiopoietin 2 (Ang2) as a target of miR-30. MiR-30 overexpression reduces Ang2 levels, whereas miR-30 inhibition by LNA-antimiRs induces Ang2 expression. Consistently, miR-30 reduced basal and TNF-α-induced expression of the inflammatory cell­cell adhesion molecules E-selectin, ICAM1 and VCAM1, which was rescued by stimulation with exogenous Ang2. In summary, KLF2 and shear stress increase the expression of the miR-30-5p family which acts in an anti-inflammatory manner in ECs by impairing the expression of Ang2 and inflammatory cell­cell adhesion molecules. The upregulation of miR-30-5p family members may contribute to the atheroprotective effects of shear stress.

Systemic or Endoventricular Thrombolysis to Treat HeartWare Left Ventricle Assist Device Thrombosis: A Clinical Dilemma.

Endoventricular thrombolytic procedure (ETP) has been used to treat continuous-flow left ventricle assist device (CF-LVAD) thrombosis. The study aims to investigate the occurrence of complications after ETP. Data were retrospectively reviewed and analyzed in a series of patients who underwent CF-LVAD followed by ETP. Since November 2010, 20 patients underwent HeartWare CF-LVAD implantation at our institute. Four patients (20%) developed pump thrombosis and underwent a total of nine ETPs with tissue plasminogen activator infused into the left ventricle. The mean age was 60.2 ± 9 years. ETP was performed via either the femoral (n = 6) or radial artery (n = 3). Five ETPs (55.5%) were complicated by left and right radial artery occlusion, two by groin hematomas, and one by femoral artery false aneurysm. ETP carries a strong risk of vascular access complications that, in CF-LVAD patients, may add to the already complex clinical profile and economic burden; thus, a less invasive treatment is advisable whenever required.