Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants.

Diabetic cardiomyopathy (DCM) is a diabetes mellitus-induced pathophysiological condition characterized by cardiac structural, functional, and metabolic changes that can result in heart failure (HF), in the absence of coronary artery disease, hypertension, and valvular heart disease. Metabolic alterations such as hyperglycemia, insulin resistance, hyperinsulinemia, and increased metabolism of free fatty acids result in oxidative stress, inflammation, advanced glycation end products formation, abnormalities in calcium homeostasis, and apoptosis that are responsible for structural remodeling. Cardiac stiffness, hypertrophy, and fibrosis eventually lead to dysfunction and HF with preserved ejection fraction and/or HF with reduced ejection fraction. In this review, we analyzed in detail the cellular and molecular mechanisms and the metabolic pathways involved in the pathophysiology of DCM. Different phenotypes are observed in DCM, and it is not clear yet if the restrictive and the dilated phenotypes are distinct or represent an evolution of the same disease. Phenotypic differences can be observed between T1DM and T2DM DCM, possibly explained by the different myocardial insulin action. Further studies are needed in order to better understand the underlying mechanisms of DCM and to identify appropriate therapeutic targets and novel strategies to prevent and reverse the progression toward heart failure in diabetic patients.

Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease.

Coronary heart disease (CHD), one of the leading causes of disability and death worldwide, is a multifactorial disease whose early diagnosis is demanding. Thus, biomarkers predicting the occurrence of this pathology are of great importance from a clinical and therapeutic standpoint. By means of a pilot study on peripheral blood cells (PBMCs) of subjects with no coronary lesions (CTR; n = 2) and patients with stable CAD (CAD; n = 2), we revealed 61 differentially methylated regions (DMRs) (18 promoter regions, 24 genes and 19 CpG islands) and 14.997 differentially methylated single CpG sites (DMCs) in CAD patients. MiRNA-seq results displayed a peculiar miRNAs profile in CAD patients with 18 upregulated and 32 downregulated miRNAs (FC ≥ ±1.5, p ≤ 0.05). An integrated analysis of genome-wide DNA methylation and miRNA-seq results indicated a significant downregulation of hsa-miR-200c-3p (FCCAD = −2.97, p ≤ 0.05) associated to the hypermethylation of two sites (genomic coordinates: chr12:7073122-7073122 and chr12:7072599-7072599) located intragenic to the miR-200c/141 genomic locus (encoding hsa-miR-200c-3p) (p-value = 0.009) in CAD patients. We extended the hsa-miR-200c-3p expression study in a larger cohort (CAD = 72, CTR = 24), confirming its reduced expression level in CAD patients (FCCAD = −2; p = 0.02). However, when we analyzed the methylation status of the two CpG sites in the same cohort, we failed to identify significant differences. A ROC curve analysis showed good performance of hsa-miR-200c-3p expression level (AUC = 0.65; p = 0.02) in distinguishing CAD from CTR. Moreover, we found a significant positive correlation between hsa-miR-200c-3p expression and creatinine clearance (R2 = 0.212, p < 0.005, Pearson r = 0.461) in CAD patients. Finally, a phenotypic correlation performed in the CAD group revealed lower hsa-miR-200c-3p expression levels in CAD patients affected by dyslipidemia (+DLP, n = 58) (p < 0.01). These results indicate hsa-miR-200c-3p as potential epi-biomarker for the diagnosis and clinical progression of CAD and highlight the importance of deeper studies on the expression of this miRNA to understand its functional role in coronary artery disease development.

The Role of Gut Microbiota in the Clinical Outcome of Septic Patients: State of the Art and Future Perspectives.

Sepsis is a life-threatening multiple-organ dysfunction caused by a dysregulated host response to infection, with high mortality worldwide; 11 million deaths per year are attributable to sepsis in high-income countries. Several research groups have reported that septic patients display a dysbiotic gut microbiota, often related to high mortality. Based on current knowledge, in this narrative review, we revised original articles, clinical trials, and pilot studies to evaluate the beneficial effect of gut microbiota manipulation in clinical practice, starting from an early diagnosis of sepsis and an in-depth analysis of gut microbiota.

Recommendations in pre-procedural imaging assessment for TAVI intervention: SIC-SIRM position paper part 2 (CT and MR angiography, standard medical reporting, future perspectives).

Non-invasive cardiovascular imaging owns a pivotal role in the preoperative assessment of patient candidates for transcatheter aortic valve implantation (TAVI), providing a wide range of crucial information to select the patients who will benefit the most and have the procedure done safely. This document has been developed by a joined group of experts of the Italian Society of Cardiology and the Italian Society of Medical and Interventional Radiology and aims to produce an updated consensus statement about the pre-procedural imaging assessment in candidate patients for TAVI intervention. The writing committee consisted of members and experts of both societies who worked jointly to develop a more integrated approach in the field of cardiac and vascular radiology. Part 2 of the document will cover CT and MR angiography, standard medical reporting, and future perspectives.

Epigenetic Modifications and Non-Coding RNA in Diabetes-Mellitus-Induced Coronary Artery Disease: Pathophysiological Link and New Therapeutic Frontiers.

Diabetes mellitus (DM) is a glucose metabolism disorder characterized by chronic hyperglycemia resulting from a deficit of insulin production and/or action. DM affects more than 1 in 10 adults, and it is associated with an increased risk of cardiovascular morbidity and mortality. Cardiovascular disease (CVD) accounts for two thirds of the overall deaths in diabetic patients, with coronary artery disease (CAD) and ischemic cardiomyopathy as the main contributors. Hyperglycemic damage on vascular endothelial cells leading to endothelial dysfunction represents the main initiating factor in the pathogenesis of diabetic vascular complications; however, the underlying pathophysiological mechanisms are still not entirely understood. This review addresses the current knowledge on the pathophysiological links between DM and CAD with a focus on the role of epigenetic modifications, including DNA methylation, histone modifications and noncoding RNA control. Increased knowledge of epigenetic mechanisms has contributed to the development of new pharmacological treatments ("epidrugs") with epigenetic targets, although these approaches present several challenges. Specific epigenetic biomarkers may also be used to predict or detect the development and progression of diabetes complications. Further studies on diabetes and CAD epigenetics are needed in order to identify possible new therapeutic targets and advance personalized medicine with the prediction of individual drug responses and minimization of adverse effects.

Treatment of HFpEF beyond the SGLT2-Is: Does the Addition of GLP-1 RA Improve Cardiometabolic Risk and Outcomes in Diabetic Patients?

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome frequently seen in elderly patients, the incidence of which is steadily increasing due to an ageing population and the increasing incidence of diseases, such as diabetes, hypertension, obesity, chronic renal failure, and so on. It is a multifactorial disease with different phenotypic aspects that share left ventricular diastolic dysfunction, and is the cause of about 50% of hospitalizations for heart failure in the Western world. Due to the complexity of the disease, no specific therapies have been identified for a long time. Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2-Is) and Glucagon-Like Peptide Receptor Agonists (GLP-1 RAs) are antidiabetic drugs that have been shown to positively affect heart and kidney diseases. For SGLT2-Is, there are precise data on their potential benefits in heart failure with reduced ejection fraction (HFrEF) as well as in HFpEF; however, insufficient evidence is available for GLP-1 RAs. This review addresses the current knowledge on the cardiac effects and potential benefits of combined therapy with SGLT2-Is and GLP-1RAs in patients with HFpEF.

Quantum Coherence in Loopless Superconductive Networks.

Measurements indicating that planar networks of superconductive islands connected by Josephson junctions display long-range quantum coherence are reported. The networks consist of superconducting islands connected by Josephson junctions and have a tree-like topological structure containing no loops. Enhancements of superconductive gaps over specific branches of the networks and sharp increases in pair currents are the main signatures of the coherent states. In order to unambiguously attribute the observed effects to branches being embedded in the networks, comparisons with geometrically equivalent-but isolated-counterparts are reported. Tuning the Josephson coupling energy by an external magnetic field generates increases in the Josephson currents, along the above-mentioned specific branches, which follow a functional dependence typical of phase transitions. Results are presented for double comb and star geometry networks, and in both cases, the observed effects provide positive quantitative evidence of the predictions of existing theoretical models.

Hepatic fibrosis of any origin in a large population of type 2 diabetes patients.

BACKGROUND AND AIMS: Excess morbidity and mortality from chronic liver disease in type 2 diabetes (T2DM) is recognized; however, the clinical features associated with liver fibrosis (LF) of any origin are poorly known. Metabolic status and/or coexisting complications over time may play a role. METHODS AND RESULTS: We interrogated the database of the diabetes unit network of Piedmont (Italy) (71,285 T2DM patients) and calculated a fibrosis-4 score (FIB-4) from data recorded between 2006 and 2019. Comorbidities were obtained by linkage with hospital data. The study population was subdivided by aetiology of LF (alcoholic, viral, metabolic). Associations between upper level of FIB-4 and demographic and clinical variables were evaluated separately for each group using robust Poisson models and presented as prevalence ratios. Nearly one-quarter (24%) of T2DM patients had some form of LF: viral (0.44%) and alcoholic (0.53%) forms were far less frequent than metabolic ones (22.7%). Only 1 out of 5 of these patients had a history of known cirrhosis. Age, male sex, duration of diabetes, coronary disease, hyperuricemia, renal failure, and features of liver failure (e.g., lower body-mass index, lipid and HbA1c levels) were positively associated with metabolic LF. More intensive treatments with insulin and segretagogue emerged as a significant predictive indicators of LF of metabolic origin. CONCLUSION: A sizeable proportion of T2DM patients has some degree of LF, mainly of metabolic origin and often undiagnosed. There is a need to clarify whether the link between insulin therapy and advanced LF is causal or not.

Profiloplasty in One Session Versus Single Treatment Areas.

BACKGROUND: Fillers have been widely used to improve facial profile, and a better result is obtained if the entire profile is treated at the same time. OBJECTIVE: To compare the outcomes of 2 groups of patients: the former undergoing a treatment in a single area to improve the facial profile, and the latter undergoing a total profiloplasty reharmonization in 1 session. MATERIALS AND METHODS: The outcomes of this study have been evaluated using both the angle of convexity and the Global Aesthetic Improvement Scale method. RESULTS: This study demonstrates that the approval rating increases by 56.3% for patients, 81.3% for the practitioner, and 76.3% for an independent practitioner when a synchronous treatment is used to improve the facial profile as compared with a single treatment of 1 profile area. CONCLUSION: The profiloplasty treatment in 1 session allows the achievement of a more harmonic facial profile and increases the patient's approval as compared with treatments of a single facial area.

Multidimensional Prognostic Index (MPI) in elderly patients with acute myocardial infarction.

BACKGROUND: Management of elderly patients with acute myocardial infarction (AMI) is challenging due to lack of knowledge about the link between fragility, outcomes and interventional procedures. AIMS: The aim of this study was to establish the prognostic role of the Multidimensional Prognostic Index (MPI) in elderly with AMI. METHODS: A total of 241 patients ≥ 65 years old with AMI were continuously enrolled in this prospective study and divided into three groups according to the MPI score. The primary endpoint was 30-day mortality. Secondary endpoints were 6-month mortality and rate of adverse events. RESULTS: In-hospital overall mortality rate was higher in MPI-3 (p = 0.009). Patients of MPI-3 had a significantly higher mortality rate regarding the primary endpoint with 30-day survival of 78.9%, compared to 97.4% and 97.2%, in MPI-1, MPI-2 (p < 0.001), respectively. The survival rate progressively decreased in the three MPI classes of risk with a 6-month survival of 96.5%, 96.3%, 73.7% in groups MPI-1, MPI-2, and MPI-3 (p < 0.001). Longer length of in-hospital stay was observed in MPI-3 group. In-hospital complications were more frequent in higher MPI score. DISCUSSION: Our findings are in agreement with the results of other studies that evaluated the risk of in-hospital complications and mortality in older patients. In our "real-world" population of elderly hospitalized for AMI we observed poorer outcomes in patients belonged to higher MPI groups. CONCLUSIONS: In the setting of AMI, MPI may be very useful in the daily clinical practice to manage older patients and predict the risk of in-hospital and follow-up complications.

Prevalence, management, and outcome of adverse rhythm disorders in takotsubo syndrome: insights from the international multicenter GEIST registry.

One important complication related to takotsubo syndrome (TTS) is adverse rhythm disorders. Our study was conducted to determine the incidence and management of adverse rhythm disorders in TTS and its long-term prognostic impact. We analyzed 906 TTS patients from 9 European centers. Patients were divided into the adverse rhythm disorders group (encompassing ventricular tachycardia, ventricular fibrillation, torsade de pointes, and asystole or complete atrioventricular block) and non-adverse rhythm disorders group. In our study cohort, we identified 67 (7.4%) patients with presence of adverse rhythm disorders. TTS patients were followed up over a period of 2.8 years. In the adverse rhythm disorders group, 18% of patients presented adverse rhythm disorders before hospital admission. Asystole and/or AV block were significantly more presented before admission (13 patients versus 8 patients; p < 0.01), whereas ventricular tachyarrhythmias were more presented in-hospital (4 patients versus 42 patients; p < 0.01). Adverse rhythm disorders patients suffered more frequently from cardiogenic shock (31% versus 7.6%, p < 0.01) and in-hospital death (10.9% versus 3.6%; p < 0.01). Furthermore, the long-term survival was significantly impaired in adverse rhythm disorders patients as compared with non-adverse rhythm disorders patients; (log-rank p < 0.01). Using multivariate Cox regression analysis, cardiogenic shock (HR 2.86, 95% CI 1.1-6.9; p = 0.02) was identified as independent predictors of adverse rhythm disorders. The short- and long-term mortality rate of TTS patients presenting with adverse rhythm disorders was significantly higher than in TTS patients presenting without it. Therefore, TTS patients with adverse rhythm disorders should be carefully monitored during hospital stay and at long-term follow-up.

Safety and efficacy of polymer-free biolimus-eluting stents versus ultrathin stents in unprotected left main or coronary bifurcation: A propensity score analysis from the RAIN and CHANCE registries.

OBJECTIVES: Evaluate safety and efficacy of polymer-free biolimus-eluting stents (PF-BESs) versus ultrathin stents in unprotected left main (ULM) or bifurcation. BACKGROUND: PF-BESs due to reduced length of dual antiplatelet therapy (DAPT) are increasingly used. However, there are limited data about safety and efficacy for ULM or bifurcation. METHODS: We selected all-patients treated for ULM or bifurcation from two multicenter real life registries (RAIN [NCT03544294] evaluating ultrathin stents, CHANCE [NCT03622203] appraising PF-BES). After propensity score with matching, the primary endpoint was major adverse cardiac events (MACE; a composite of all-cause death, myocardial infarction, target lesion revascularization [TLR], and stent thrombosis [ST]), while its components along with target vessel revascularization (TVR) secondary endpoints. RESULTS: Three thousand and three patients treated with ultrathin stents and 446 with PF-BESs, resulting respectively in 562 and 281 after propensity score with matching (33 and 22%, respectively, with ULM disease). After 12 (8-20) months, rates of MACE were similar (9 vs. 8%, p = 0.56) without difference in TLR and ST (3.0 vs. 1.7%, p = .19 and 1.8 vs. 1.1%, p = .42). These results were consistent for ULM group (3 vs. 1.7% and 1.8 vs. 1.1%, p = .49 and .76), for non-ULM group (2.1 vs. 3.4%, p = .56 and 1.2 vs. 1.7%, p = .78) and for two-stent strategy (8.7 vs. 4.5% and 4.3 vs. 3.2%, p = .75 and .91). Among patients treated with 1 month of DAPT in both groups, those with ultrathin stents experienced higher rates of MACE related to all-cause death (22 vs. 12%, p = .04) with higher although not significant rates of ST (3 vs. 0%, p = .45). CONCLUSIONS: PF-BES implanted on ULM or BiF offered freedom from TLR and ST comparable to ultrathin stents. PF-BESs patients assuming DAPT for 1 month experienced a lower despite not significant incidence of ST.

Impact of structural features of very thin stents implanted in unprotected left main or coronary bifurcations on clinical outcomes.

OBJECTIVES: To evaluate the independent clinical impact of stent structural features in a large cohort of patients undergoing unprotected left main (ULM) or coronary bifurcation percutaneous coronary intervention (PCI) with a range of very thin strut stents. BACKGROUND: Clinical impact of structural features of contemporary stents remains to be defined. METHODS: All consecutive patients enrolled in the veRy thin stents for patients with left mAIn or bifurcatioN in real life (RAIN) registry were included. The following stent structural features were studied: antiproliferative drugs (everolimus vs. sirolimus vs. zotarolimus), strut material (platinum-chromium vs. cobalt-chromium), polymer (bioresorbable vs. durable), number of crowns (<8 vs. ≥8) and number of connectors (<3 vs. ≥3). For small diameter stents (≤2.5 mm), struct thickness (74 vs. 80/81 µm) was also tested. Target lesion failure (TLF), a composite of target lesion revascularization and stent thrombosis, was the primary endpoint. Multivariate analysis was performed with Cox regression models. RESULTS: Out of 2,707 patients, 110 (4.1%) experienced a TLF event after 16 months (12-18). After adjustment for confounders, an increased number of connectors (adjusted hazard ratio [adj-HR] 0.62, 95% confidence interval (CI) 0.39-0.99, p = .04) reduced risk of TLF, driven by stents with ≥2.5 mm diameter (HR 0.54, 95% CI 0.32-0.93, p = .02). This independent relationship was lost for stents with diameter <2.5 mm, where only strut thickness appeared to impact. Conversely, no independent relationship of polymer type, number of crowns, and the specific limus-family eluted drug with outcomes was observed. CONCLUSIONS: Among a range of contemporary very thin stent models, an increased number of connectors improved device-related outcomes in this investigated high-risk procedural setting.

Impact of severe and symptomatic hypoglycemia on quality of life and fear of hypoglycemia in type 1 and type 2 diabetes. Results of the Hypos-1 observational study.

BACKGROUND AND AIMS: Hypoglycemia represents a relevant burden in people with diabetes. Consequences of hypoglycemia/fear of hypoglycemia on quality of life (QoL) and behaviors of patients with T1DM and T2DM were assessed. METHODS AND RESULTS: HYPOS-1 was an observational retrospective study. Fear of hypoglycemia (Fear of Hypoglycemia Questionnaire, FHQ), general health status (visual analog scale of EuroQol questionnaire, EQ5D-VAS) psychological well-being (WHO-5 well being index, WHO-5), diabetes related distress (Problem Areas in Diabetes 5, PAID-5), and corrective/preventive behaviors following hypoglycemia were compared between people with and without previous experience of severe and symptomatic hypoglycemia and by tertiles of FHQ scores. A multivariate analysis was performed to identify factors associated with the likelihood of being in the third tertile of FHQ score. Overall, 2229 patients were involved. Severe hypoglycemia had statistically significant and clinically relevant (measured as effect sizes) negative impact on EQ5D-VAS, WHO-5, PAID-5, and FHQ both in T1DM and T2DM. In T2DM, symptomatic episodes had similar impact of severe hypoglycemia. Moving from the first to the third FHQ tertile, lower scores of EQ-5D VAS and WHO-5, and higher levels of PAID-5 were found. Patients in the third tertile performed more frequently corrective/preventive actions that negatively impact on metabolic control. Previous hypoglycemia, insulin treatment, female gender, age, and school education were the independent factors associated with increased likelihood to be in the third tertile. CONCLUSION: Not only severe but also symptomatic hypoglycemia negatively affect patient QoL, especially in T2DM. Addressing fear of hypoglycemia should be a goal of diabetes education.

Upper Eyelid Filling Approach [U.E.F.A.] Technique: State of the Art After 500 Consecutive Patients.

BACKGROUND: Lately, it has become evident that eye physical aging is mainly due to depletion of the upper eyelid fat causing laxity and wrinkles of the eyelid skin, and new therapeutic strategies aimed at solving the volume loss have appeared in the literature. The aim of this study is to provide a clear classification of upper eyelid aging after 500 consecutive cases and to present a standardization of the therapeutic approach to be adopted when using hyaluronic acid (HA) as fillers or a surgical approach. METHODS: The upper eyelid aging process of a total of 500 patients was classified based on the measurement of the pre-tarsal skin show m and the pre-septal skin show N. A total of 382 patients were treated exclusively with HA injections in the upper eyelid, 45 patients both with blepharoplasty surgery and HA filling, whereas only 73 patients underwent blepharoplasty only. RESULTS: Patient satisfaction and at least 1-year clinical follow-up were used to evaluate the results. Pre-treatment and post-treatment photographic assessment was considered as well. A total of 447 patients were women, whereas 53 were men. The correct ratio between m and N was restored in all cases. CONCLUSIONS: HA filling can be used as either the only volumization procedure or together with blepharoplasty to restore upper eyelid volume loss. The correct strategy has to be selected on the basis of a clear classification. The upper eyelid filling approach is a safe, manageable, lasting and low-cost technique providing excellent results when the correct procedure is followed. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Infections, atherosclerosis, and coronary heart disease.

Atherosclerosis is a chronic inflammatory disease. Pathophysiological similarities between chronic infections and atherosclerosis triggered interest in a clinical association between these conditions. Various infectious microbes have been linked to atherosclerotic vascular disease in epidemiological studies. However, this association failed to satisfy the Koch's postulates of causation with multiple clinical trials demonstrating inefficacy of anti-infective therapies in mitigating atherosclerotic cardiovascular events. Identification of underlying pathophysiological mechanisms and experience with vaccination against various infectious agents has ushered a new avenue of efforts in the development of an anti-atherosclerotic vaccine. Studies in animal models have identified various innate and adaptive immune pathways in atherosclerosis. In this review, we discuss the patho-biological link between chronic infections and atherosclerosis, evaluate existing evidence of animal and human trials on the association between infections and cardiovascular disease and introduce the concept of an anti-atherosclerotic vaccine.

Role of Inflammation in Heart Failure.

PURPOSE OF REVIEW: This paper aims to discuss the interactions between inflammatory cytokines, immune cells, and heart failure (HF). The association of heart failure with inflammation has led to multiple studies on anti-inflammatory agents in acute and chronic heart failure. RECENT FINDINGS: Recent findings have implicated leukocytes subclasses and multiple inflammatory mediators in the progression of heart failure and cardiovascular disease. Studies have discovered further details on the interaction between immune cells-particularly macrophages and lymphocytes-and inflammation. There are both cell-mediated and cytokine-mediated pathways of inflammation, which are interconnected. Additionally, a number of markers have been used and studied in heart failure disease progression. In this review, we discuss inflammatory biomarkers and immune cell mediators involved in HF. We will focus on the correlations and role of these inflammatory mediators in the genesis of HF. We will also discuss the evidence on beneficial effects of anti-inflammatory agents in the setting of chronic HF.

Advanced myocardial tissue characterisation by a multi-component CMR protocol in patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) patients are at increased risk of suffering from adverse cardiovascular events. Cardiovascular magnetic resonance (CMR) mapping techniques might be appropriate tools to complement late gadolinium enhancement (LGE) for the assessment of myocardial involvement. This study aimed to perform advanced myocardial tissue characterisation in RA patients by a multicomponent CMR protocol. METHODS: 22 RA patients were prospectively enrolled and underwent CMR, including LGE and T1/T2 mapping sequences; 20 volunteers served as controls. RESULTS: Mean LV-EF was 66%; prevalence of LGE was 18%. RA patients had increased native T1 (985 vs. 959 ms, p = 0.03), expanded extracellular volume (ECV) (27 vs. 25%, p = 0.02) and higher T2 values (52 vs. 49 ms, p < 0.001) compared to controls irrespective of the presence of LGE. T2 mapping showed the highest prevalence of values beyond the 95% percentile of controls. CONCLUSION: RA patients demonstrated higher T1, ECV and T2 values compared to controls, with most significant differences for T2. Since these results seem to be independent of the presence of LGE, advanced myocardial tissue characterisation including CMR mapping techniques in addition to LGE-CMR might be useful in the evaluation of myocardial involvement in RA patients. KEY POINTS: • RA patients had higher T1, ECV and T2 values compared to controls. • Most significant differences were observed for T2. • Our results seem to be independent of the presence of LGE. • Mapping might be useful in the evaluation of myocardial involvement in RA.

Long-Term Results of Aortic Root Surgery in Marfan Syndrome Patients: A Single-Center Experience.

BACKGROUND AND AIM OF THE STUDY: The study aim was to compare long-term results of Marfan syndrome (MFS) patients affected by aortic root disease undergoing aortic root replacement with the Bentall or David operation. METHODS: Since 1994, a total of 59 patients has been followed at the authors' Marfan Center, having undergone either a Bentall operation (Bentall group, n = 30) or a David operation (David group, n = 29). RESULTS: No operative mortality was recorded. After 20 years (mean follow up 97 ± 82 months; range 1 to 369 months) no prosthesis-related major bleeding or thromboembolic events had been observed; the 20-year survival was 94 ± 6% in the Bentall group, and 100% in the David group (p = 0.32). Freedom from reintervention for aortic valve dysfunction was 100% in the Bentall group, and 75 ± 13% in the David group (p = 0.04). This inter-group difference became relevant after the first eight-year period of follow-up, and was mainly associated with a particular familiar genetic phenotype involving three out of four reoperated patients. Freedom from all-cause death, myocardial infarction, stroke, prosthetic valve-related complications, and reintervention on any aortic segment was 69 ± 12% in the Bentall group, and 67 ± 14% in the David group (p = 0.33). CONCLUSIONS: The Bentall and David operations are both associated with satisfactory long-term results in MFS patients. The low rate of valve prosthesis-related complications suggested that the Bentall operation would continue to be a standard surgical treatment. The reimplantation technique, adopted for less-dilated aortas, provides satisfactory freedom from reoperation. Careful attention should be paid to the reimplantation technique in patients affected by a serious familiar genetic phenotype.