Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.

Human epicardial adipose tissue expresses glucose-dependent insulinotropic polypeptide, glucagon, and glucagon-like peptide-1 receptors as potential targets of pleiotropic therapies.

AIMS: Human epicardial adipose tissue (EAT) plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Thus, it might be a therapeutic target for pharmaceutical compounds acting on G-protein-coupled receptors, such as those for glucose-dependent insulinotropic polypeptide (GIP), glucagon (GCG), and glucagon-like peptide-1 (GLP-1), whose selective stimulation with innovative drugs has demonstrated beneficial cardiovascular effects. The precise mechanism of these novel drugs and their tissue and cellular target(s) need to be better understood. We evaluate whether human EAT expresses GIP, GCG, and GLP-1 receptors and whether their presence is related to EAT transcriptome. We also investigated protein expression and cell-type localization specifically for GIP receptor (GIPR) and glucagon receptor (GCGR). METHODS AND RESULTS: Epicardial adipose tissue samples were collected from 33 patients affected by cardiovascular diseases undergoing open heart surgery (90.9% males, age 67.2 ± 10.5 years mean ± SD). Microarray and immunohistochemistry analyses were performed. Microarray analysis showed that GIPR and GCGR messenger ribonucleic acids (mRNAs) are expressed in EAT, beyond confirming the previously found GLP-1 [3776 ± 1377 arbitrary unit (A.U.), 17.77 ± 14.91 A.U., and 3.41 ± 2.27 A.U., respectively]. The immunohistochemical analysis consistently indicates that GIPR and GCGR are expressed in EAT, mainly in macrophages, isolated, and in crown-like structures. In contrast, only some mature adipocytes of different sizes showed cytoplasmic immunostaining, similar to endothelial cells and pericytes in the capillaries and pre-capillary vascular structures. Notably, EAT GIPR is statistically associated with the low expression of genes involved in free fatty acid (FFA) oxidation and transport and those promoting FFA biosynthesis and adipogenesis (P < 0.01). Epicardial adipose tissue GCGR, in turn, is related to genes involved in FFA transport, mitochondrial fatty acid oxidation, and white-to-brown adipocyte differentiation, in addition to genes involved in the reduction of fatty acid biosynthesis and adipogenesis (P < 0.01). CONCLUSIONS: Having reported the expression of the GLP-1 receptor previously, here, we showed that GIPR and GCGR similarly present at mRNA and protein levels in human EAT, particularly in macrophages and partially adipocytes, suggesting these G-protein-coupled receptors as pharmacological targets on the ongoing innovative drugs, which seem cardiometabolically healthy well beyond their effects on glucose and body weight.

Human epicardial adipose tissue (EAT) is a unique and multifunctional fat compartment of the heart. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Due to its distinctive transcriptome and functional proximity to the heart, EAT can play a key role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Clinically, EAT, given its rapid metabolism and simple measurability, can be considered a novel therapeutic target, owing to its responsiveness to drugs with pleiotropic and clear beneficial cardiovascular effects such as the glucagon-like peptide-1 receptor (GLP-1R) agonists.Human EAT is found to express the genes encoding the receptors of glucose-dependent insulinotropic polypeptide receptor (GIPR), glucagon receptor (GCGR), and GLP-1. The immunohistochemistry indicates that GIP and GCG receptor proteins are present in EAT samples. Epicardial adipose tissue GIPR is inversely associated with genes involved in free fatty acid (FFA) oxidation and transport and with genes promoting FFA biosynthesis and adipogenesis. Epicardial adipose tissue GCGR is correlated with genes promoting FFA transport and activation for mitochondrial beta-oxidation and white-to-brown adipocyte differentiation and with genes reducing FFA biosynthesis and adipogenesis.As the myocardium relies mostly on FFAs as fuel and is in direct contiguity with EAT, these findings may have a great importance for the modulation of the myocardial activity and performance. Given the emerging use and cardiovascular effects of GLP-1R agonists, dual GIPR/GLP-1R agonists, and GLP-1R/GIPR/GCGR triagonists, we believe that pharmacologically targeting and potentially modulating organ-specific fat depots through G-protein­coupled receptors may produce beneficial cardiovascular and metabolic effects.

Elucidating the mechanisms underlying left ventricular function recovery in patients with ischemic heart failure undergoing surgical remodeling: A 3-dimensional ultrasound analysis.

OBJECTIVE: The study objective was to elucidate the mechanisms of left ventricle functional recovery in terms of endocardial contractility and synchronicity after surgical ventricular reconstruction. METHODS: Real-time 3-dimensional transthoracic echocardiography was performed on 20 patients with anterior left ventricle remodeling and ischemic heart failure before surgical ventricular reconstruction and at 6-month follow-up, and on 15 healthy controls matched by age and body surface area. Real-time 3-dimensional transthoracic echocardiography datasets were analyzed through TomTec software (4D LV-Analysis; TomTec Imaging Systems GmbH, Unterschleissheim, Germany): Left ventricle volumes, ejection fraction, and global longitudinal strain were computed; the time-dependent endocardial surface yielded by 3-dimensional speckle-tracking echocardiography was postprocessed through in-house software to quantify local systolic minimum principal strain as a measure of fiber shortening and mechanical dispersion as a measure of fiber synchronicity. RESULTS: Compared with controls, patients with heart failure before surgical ventricular reconstruction showed lower ejection fraction (P < .0001) and significantly impaired mechanical dispersion (P < .0001) and minimum principal strain (P < .0001); the latter worsened progressively from left ventricle base to apex. After surgical ventricular reconstruction, global longitudinal strain improved from -6.7% to -11.3% (P < .0001); mechanical dispersion decreased in every left ventricle region (P ≤ .017) and mostly in the basal region, where computed mechanical dispersion values were comparable to physiologic values (P ≥ .046); minimum principal strain improved mostly in the basal region, changing from -16.6% to -22.3% (P = .0027). CONCLUSIONS: At 6-month follow-up, surgical ventricular reconstruction was associated with significant recovery in global left ventricle function, improved mechanical dispersion indicating a more synchronous left ventricle contraction, and improved left ventricle fiber shortening mostly in the basal region, suggesting the major role of the remote myocardium in enhancing left ventricle functional recovery.

Long-term results of surgical ventricular reconstruction and comparison with the Surgical Treatment for Ischemic Heart Failure trial.

OBJECTIVE: The role of surgical ventricular reconstruction (SVR) in patients with ischemic cardiomyopathy is controversial. Observational series and the Surgical Treatment of IsChemic Heart failure (STICH) trial reported contradictory results. SVR is highly dependent on operator experience. The aim of this study is to compare the long-term results of SVR between a high-volume SVR institution and the STICH trial using individual patient data. METHODS: Patients undergoing SVR at San Donato Hospital (Milan) were compared with patients undergoing SVR in STICH (as-treated principle) by inverse probability treatment-weighted Cox regression. The primary outcome was all-cause mortality. RESULTS: The San Donato cohort included 725 patients, whereas the STICH cohort included 501. Compared with the STICH-SVR cohort, San Donato patients were older (66.0, lower quartile, upper quartile [Q1, Q3: 58.0, 72.0] vs 61.9 [Q1, Q3: 55.1, 68.8], P < .001) and with lower left ventricular end-systolic volume index at baseline (LVESVI: 77.0 [Q1, Q3: 59.0, 97.0] vs 80.8 [Q1, Q3: 58.5, 106.8], P = .02). Propensity score weighting yielded 2 similar cohorts. At 4-year follow-up, mortality was significantly lower in the San Donato cohort compared with the STICH-SVR cohort (adjusted hazard ratio, 0.71; 95% confidence interval, 0.53-0.95; P = .001). Greater postoperative LVESVI was independently associated with mortality (hazard ratio, 1.02; 95% confidence interval, 1.01-1.03). At 4 to 6 months of follow-up, the mean reduction of LVESVI in the San Donato cohort was 39.6%, versus 10.7% in the STICH-SVR cohort (P < .001). CONCLUSIONS: Patients with postinfarction LV remodeling undergoing SVR at a high-volume SVR institution had better long-term results than those reported in the STICH trial, suggesting that a new trial testing the SVR hypothesis may be warranted.

Surgical Ventricular Restoration for Ischemic Heart Failure: A Glance at a Real-World Population.

Surgical ventricular restoration (SVR) has repeatedly been suggested as a viable therapeutic strategy for ischemic heart failure (HF) patients, although the survival benefit is still debated. We investigated a real-world population treated with SVR in a single center with high case volumes. From July 2001 to June 2017, 648 patients (111 females) underwent SVR; coronary surgery was performed in 582 patients. Data were analyzed by dividing the population into two groups: Group I (371 patients operated between July 2001 and December 2007) and Group II (277 patients operated between January 2008 and June 2017). At baseline, Group I patients were more symptomatic for angina (47.4% versus 19.4%, p < 0.0001) and less symptomatic for HF (NYHA class III/IV, 46.3% versus 57%, p = 0.0071). The end-diastolic volume (106 mL/m2 versus 118.3 mL/m2, p < 0.0001) and the end-systolic volume (70.5 mL/m2 versus 81.5 mL/m2, p < 0.0001) were lower in Group I. The presence of 3-vessel coronary artery disease (CAD) was higher in Group I (73.3% versus 59.2%, p < 0.0001). Thirty-day mortality (6.64%) was similar in the two groups (p = 0.4475). The Kaplan−Meier estimate for all-cause mortality for the entire population was 13% at 2 years, 19.2% at 4 years and 36.6% at 8 years, and the probability was not different between groups (Log-rank = 0.11). In a real-world ischemic HF population, SVR may be carried out with favorable results; in patients with worse LV remodeling and less extensive CAD, SVR showed a trend toward a better outcome.

Comparison of Four-Dimensional Magnetic Resonance Imaging Analysis of Left Ventricular Fluid Dynamics and Energetics in Ischemic and Restrictive Cardiomyopathies.

BACKGROUND: Time-resolved three-directional velocity-encoded (4D flow) magnetic resonance imaging (MRI) enables the quantification of left ventricular (LV) intracavitary fluid dynamics and energetics, providing mechanistic insight into LV dysfunctions. Before becoming a support to diagnosis and patient stratification, this analysis should prove capable of discriminating between clearly different LV derangements. PURPOSE: To investigate the potential of 4D flow in identifying fluid dynamic and energetics derangements in ischemic and restrictive LV cardiomyopathies. STUDY TYPE: Prospective observational study. POPULATION: Ten patients with post-ischemic cardiomyopathy (ICM), 10 patients with cardiac light-chain cardiac amyloidosis (AL-CA), and 10 healthy controls were included. FIELD STRENGTH/SEQUENCE: 1.5 T/balanced steady-state free precession cine and 4D flow sequences. ASSESSMENT: Flow was divided into four components: direct flow (DF), retained inflow, delayed ejection flow, and residual volume (RV). Demographics, LV morphology, flow components, global and regional energetics (volume-normalized kinetic energy [KEV ] and viscous energy loss [ELV ]), and pressure-derived hemodynamic force (HDF) were compared between the three groups. STATISTICAL TESTS: Intergroup differences in flow components were tested by one-way analysis of variance (ANOVA); differences in energetic variables and peak HDF were tested by two-way ANOVA. A P-value of <0.05 was considered significant. RESULTS: ICM patients exhibited the following statistically significant alterations vs. controls: reduced KEV , mostly in the basal region, in systole (-44%) and in diastole (-37%); altered flow components, with reduced DF (-33%) and increased RV (+26%); and reduced basal-apical HDF component on average by 63% at peak systole. AL-CA patients exhibited the following alterations vs. controls: significantly reduced KEV at the E-wave peak in the basal segment (-34%); albeit nonstatistically significant, increased peaks and altered time-course of the HDF basal-apical component in diastole and slightly reduced HDF components in systole. DATA CONCLUSION: The analysis of multiple 4D flow-derived parameters highlighted fluid dynamic alterations associated with systolic and diastolic dysfunctions in ICM and AL-CA patients, respectively. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Prognostic value of natriuretic peptides and restrictive filling pattern before surgical ventricular restoration.

OBJECTIVE: Both increased natriuretic peptide levels and restrictive filling pattern (RFP) are important risk predictors in patients with heart failure. The aim of this study was to examine the role of the combined use of natriuretic peptide and RFP for the prognostic stratification of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration in the Biomarker Plus study. METHODS: A total of 186 patients (aged 64 ± 10 years) underwent echocardiographic study and N-terminal pro-B-type natriuretic peptide assay at baseline (before surgical ventricular restoration). Patients were divided into 4 groups depending on baseline diastolic filling pattern (RFP/no RFP) and N-terminal pro-B-type natriuretic peptide level (less than or greater than or equal to the upper tertile value of 2003 ŋg/L). RFP was defined as E/A ratio ≥2. All-cause death or heart failure hospitalizations within 36-month follow-up were analyzed. RESULTS: Despite similar ejection fraction, volumes, and mass, the 4 groups presented distinct clinical and structural pattern of presurgical ventricular restoration ventricular remodeling and significantly different clinical outcome after surgical unloading. During follow-up, 67 patients died or were hospitalized for heart failure (36%). High N-terminal pro-B-type natriuretic peptide levels and RFP, considered individually, were significantly associated with outcome (P < .0001). The combination of both was associated with the highest adjusted hazard of adverse events (hazard ratio, 3.63; 95% CI, 1.73-7.6; P < .0001). CONCLUSIONS: The simultaneous use of 2 markers, 1 biological and 1 echocardiographic, may allow better prognostic stratification and characterization of the distinct structural and clinical phenotypes in a population of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration. This approach could be useful in the decision-making process to guide treatment choices in patients with ischemic cardiomyopathy.

Results of surgical ventricular reconstruction in a specialized center and in comparison to the STICH trial: Rationale and study protocol for a patient-level pooled analysis.

INTRODUCTION: Post-infarction left ventricular remodeling is associated with increased mortality in patients with ischemic heart disease. Surgical ventricular reconstruction (SVR) in addition to coronary artery bypass grafting (CABG) has been proposed to reduce left ventricular volume and improve clinical outcomes. The Surgical Treatment for Ischemic Heart Failure (STICH) trial found that the addition of SVR to CABG did not reduce the rates of death or rehospitalization in the 5 years after surgery compared to CABG alone. Like all randomized trials, STICH has limitations and it has been hypothesized that it may have underestimated the treatment effect of SVR. The aim of this study is to evaluate the results of SVR in one of the largest contemporary single-center series and to compare the results with those of the STICH trial using individual patient's data. METHODS AND ANALYSIS: Individual data of patients who underwent SVR with or without CABG will be obtained from San Donato University Hospital in Milan. Using multivariable Cox regression analysis, significant prognostic indicators in this cohort will be identified. We will then compare the San Donato cohort to individual patient's data from the SVR arm of Hypothesis 2 of the STICH trial and from both arms of the STICH Extended Study (STICHES). To reduce confounders, propensity score adjustment will be used for this comparison. The primary endpoint will be all-cause mortality. Data will be merged and analyzed independently at Weill Cornell Medicine in New York.

Restrictive filling pattern in ischemic cardiomyopathy: Insights after surgical ventricular restoration.

OBJECTIVE: To examine factors possibly involved in the resolution or persistence of restrictive filling pattern (RFP) after surgical ventricular restoration (SVR) in a series of patients with ischemic cardiomyopathy (ICM) and RFP. METHODS: Echocardiography was performed at baseline (pre-SVR), discharge, and follow-up in 43 patients with ICM and RFP (E/A ratio ≥2). Patients were divided into 2 groups based on E/A ratio at discharge: improved (E/A ratio <2; 22 patients) and unchanged (E/A ratio ≥2; 21 patients). RESULTS: The improved group had a significantly increased mean deceleration time (from 137 ± 22 ms to 194 ± 68 ms; P = .002) and mean A wave velocity (from 43 ± 10 cm/s to 92 ± 37 cm/s; P = .001), and decreased E/e' ratio (from 27.7 ± 9.5 to 19.2 ± 7.8; P = .01) after SVR. The unchanged group did not show any significant variations in diastolic parameters. The only significant differences at baseline between the two groups were thinner left ventricle posterior wall and lower relative wall thickness (RWT) in the unchanged group. RWT was the sole baseline parameter independently associated with persistent RFP. CONCLUSIONS: RFP was reversed after SVR in 22 of our 43 patients with ICM with a response that remained stable over time, associated with improved New York Heart Association class. RWT was the sole baseline echocardiographic parameter significantly associated with the evolution of RFP after SVR.

Comparable outcomes between genders in patients undergoing surgical ventricular reconstruction for ischaemic heart failure.

AIMS: Female sex and heart failure (HF) are considered poor prognostic factors for surgery. We aimed to investigate the association between sex and surgical outcomes in patients with ischaemic HF undergoing surgical ventricular reconstruction and coronary artery bypass grafting. METHODS AND RESULTS: From July 2001 to June 2017, 648 patients [111 women (17%) and 537 men (83%)] were referred to our centre. Follow-up continued through June 2018. All patients underwent surgical ventricular reconstruction; coronary artery bypass grafting was performed in 582 patients (90%). Primary outcome was defined as all-cause mortality. Secondary outcome included all-cause mortality or all-cause hospitalization. Women were older (70 vs. 65 years, P < 0.0001) with lower body surface area (1.70 vs. 1.86 m2 , P < 0.0001). Women had more diabetes (36% vs. 24%, P = 0.005) and a higher New York Heart Association classification (Class III/IV 65.7% vs. 47.8%, P = 0.0006), without any significant difference in medical therapy except for a higher use of oral antidiabetic agents in women (P = 0.029). At baseline, the left ventricular (LV) end-diastolic volume index was significantly lower in women [median 107.06 (80.6-127.81) vs. 113. 04 (94.33-135.52) mL/m2 , P = 0.0078] but not the LV end-systolic volume index (ESVI) [median 73.45 (51.93-96.79) vs. 77.03 (60.33-95.71) mL/m2 , P = 0.1393] and the ejection fraction (median 31% vs. 32%, P = 0.150). Women had a higher rate of anterior remodelling (90.9% vs. 79.1%, P = 0.0129), without evidence of differences in mitral valve insufficiency (P = 0.761 for Grade 0 to 4) and mitral surgery (P = 0.810). After surgery, the percentage of reduction in LV ESVI was higher in women than in men (median ΔLV ESVI -42.06 vs. -31.99, P = 0.0003). Mortality within 30 days occurred in 43 patients (6.64%): 12 women (10.81%) and 31 men (5.77%, P = 0.0522). Over a median follow-up of 9.8 years, all-cause mortality occurred in 269 patients (41.64%), without significant difference between women (45.9%) and men (40.7%). There was no evidence of difference of all-cause death between sexes (log-rank = 0.2441). When considering mortality and first hospitalization as competing events, Gray's test showed no difference of cumulative incidence functions (all-cause hospitalization, all-cause death, and combined endpoint) according to sex (P = 0.909, P = 0.445, and P = 0.429, respectively). CONCLUSIONS: In this study, long-term outcomes for women and men with ischaemic HF undergoing complex cardiac surgery were equivalent. Albeit older and more symptomatic, women should not be denied this type of cardiac surgery.

The Monitoring of Psychosocial Factors During Hospitalization Before and After Cardiac Surgery Until Discharge From Cardiac Rehabilitation: A Research Protocol.

Introduction: There is considerable evidence that psychosocial factors contribute to the etiology and prognosis of cardiac illness. Currently, in Italy, psychologists are only obligatory in the cardiac rehabilitation setting, although there are indications that patients could be experiencing distress also during other moments of hospitalization, such as on admission for cardiac surgery. Objective and Methods: The objective of this protocol is to gain more information about cardiac patients, specifically during the various moments of hospitalization for cardiac surgery, by collecting data at admission before cardiac surgery (t0), at admission to cardiac rehabilitation (t1), and at discharge (t2) at the Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Donato hospital. A psychosocial questionnaire was constructed after consulting the relevant national and international guidelines. Patients admitted for cardiac surgery and attending a rehabilitation program will be evaluated by acquiring data about their civil status, religiosity, education and work capacity, social condition (including the presence and quality of intimate relationships and support received), previous psychological and psychiatric histories, psychological status, lifestyle (including questions on nutrition, smoking, alcohol, and substance abuse), adherence to therapy, quality of life (QoL), health perception, anxiety, and depression at t0. Health perception, anxiety, and depression are also measured at t1 and t2. Discussion and Conclusion: This study is an attempt to identify the recommended psychosocial variables which need to be monitored during cardiac patients' hospitalization for cardiac surgery, through to the completion of cardiac rehabilitation. After implementing this study at the IRCCS Policlinico San Donato, attempts will be made to create studies on a national and international level to generate more evidence regarding these variables, in order to create tailor-made interventions for these patients during these specific and delicate moments.

Clinical Course of COVID-19 Infection in Patients Urgently Operated of Cardiac Surgical Procedures.

OBJECTIVE: The aim of this study was to describe the clinical course of a consecutive series of patients operated of urgent cardiac surgery during COVID-19 outbreak. BACKGROUND: In Italy, COVID outbreak has mostly occurred in the metropolitan area of Milan, and in the surrounding region of Lombardy, and previously "conventional" hospitals were converted into COVID spokes to increase ICU beds availability, and to allow only urgent CS procedures. METHODS: Among urgent CS patients (left main stenosis with unstable angina, acute endocarditis, valvular regurgitation with impending heart failure), 10 patients (mean age = 57 ± 9 years), despite a negative admission triage, developed COVID-pneumonia postoperatively, at a median of 7 days after CS. RESULTS: Patients showed typical lymphopenia, higher prothrombotic profile, and higher markers of inflammation (ferritin and interleukin-6 values). At the zenith of pulmonary distress, patients presented with severe hypoxia (median PaO2/FIO2 ratio = 116), requiring advanced noninvasive ventilation (Venturi mask and continuous positive airway pressure) in the majority of cases. All patients were treated with hydroxychloroquine, azithromycin, and low-molecular-weight heparin at anticoagulant dose. Overall in-hospital mortality was 10% (1/10), peaking 25% in patients who developed COVID pneumonia immediately after CS. The remaining patients, with late infection, were all discharged home without oxygen support, at a median of 25 days after symptom onset. CONCLUSIONS: As postoperative mortality in case of COVID pneumonia is not negligible, meticulous rules (precise triage, safe hospital path, high level of protection for health-care teams, prompt diagnosis of suspicious symptoms) should be strictly followed in patients undergoing CS during COVID pandemic. The role of therapies alternative to CS should be further assessed.

CABG Improves Outcomes in Patients With Ischemic Cardiomyopathy: 10-Year Follow-Up of the STICH Trial.

OBJECTIVES: The authors investigated the impact of coronary artery bypass grafting (CABG) on first and recurrent hospitalization in this population. BACKGROUND: In the STICH (Surgical Treatment for Ischemic Heart Failure) trial, CABG reduced all-cause death and hospitalization in patients with and ischemic cardiomyopathy and left ventricular ejection fraction <35%. METHODS: A total of 1,212 patients were randomized (610 to CABG + optimal medical therapy [CABG] and 602 to optimal medical therapy alone [MED] alone) and followed for a median of 9.8 years. All-cause and cause-specific hospitalizations were analyzed as time-to-first-event and as recurrent event analysis. RESULTS: Of the 1,212 patients, 757 died (62.4%) and 732 (60.4%) were hospitalized at least once, for a total of 2,549 total all-cause hospitalizations. Most hospitalizations (66.2%) were for cardiovascular causes, of which approximately one-half (907 or 52.9%) were for heart failure. More than 70% of all hospitalizations (1,817 or 71.3%) were recurrent events. The CABG group experienced fewer all-cause hospitalizations in the time-to-first-event (349 CABG vs. 383 MED, adjusted hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.74 to 0.98; p = 0.03) and in recurrent event analyses (1,199 CABG vs. 1,350 MED, HR: 0.78, 95% CI: 0.65 to 0.94; p < 0.001). This was driven by fewer total cardiovascular (CV) hospitalizations (744 vs. 968; p < 0.001, adjusted HR: 0.66, 95% CI: 0.55 to 0.81; p = 0.001), the majority of which were due to HF (395 vs. 512; p < 0.001, adjusted HR: 0.68, 95% CI: 0.52-0.89; p = 0.005). We did not observe a difference in non-CV events. CONCLUSIONS: CABG reduces all-cause, CV, and HF hospitalizations in time-to-first-event and recurrent event analyses. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

Myocardial reconstruction in ischaemic cardiomyopathy.

An increase in left ventricular volume after a myocardial infarction is a key component of the adverse remodelling process leading to chamber dysfunction, heart failure and an unfavourable outcome. Hence, the therapeutic strategies have been designed to reverse the remodelling process by medical therapy, devices or surgical strategies. Surgical ventricular reconstruction primarily combined with myocardial revascularization has been introduced as an optional intervention aimed to reduce the left ventricle through resection of the scar tissue and is recommended in selected patients with predominant heart failure symptoms, and with myocardial scarring and moderate left ventricular remodelling. This review outlines the rationale and the technique for reconstructing the left ventricle and the possible indications for using that technique, based on experiences from the centre with the largest international experience. The major contributions in the literature are briefly discussed.

Longitudinal profile of NT-proBNP levels in ischemic heart failure patients undergoing surgical ventricular reconstruction: The Biomarker Plus study.

BACKGROUND: Plasma concentrations of natriuretic peptides have been shown to predict prognosis in heart failure (HF) patients with left ventricle (LV) dysfunction. It is still unclear if measurements after cardiac surgery are associated with any effect on the outcome. We aimed to prospectively investigate the longitudinal profile of serial evaluations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in ischemic HF patients undergoing Surgical Ventricular Reconstruction (SVR) and how NT-proBNP levels at different time-points are associated with the outcome. METHODS: One hundred and forty-three patients (122 men, 64 ±â€¯9 years old) with post-infarction LV remodeling referred to our Center for SVR had an assessment of NT-proBNP levels before surgery and 6, 12 and 18 months after surgery. The analysis was performed using the logarithm of the biomarker and joint modeling of serial measurements through mixed models together with Cox regression to analyze time to event data. RESULTS: The average level of the biomarker decreased by about 50% during the first year after the operation. Time-varying NT-proBNP levels were associated with the hazard of: 1% increase in NT-proBNP during the follow-up was associated with 1.5% increase of the risk of the composite event (95% CI: 1.0%, 2.6%) and with 4.2% increase of the risk of death (95% CI: 2.2%, 8.2%). CONCLUSIONS: Serial profiles (either in increasing or in decreasing) at different time points are associated with a modulation of the risk of adverse events and, therefore, are important indicators for monitoring the evolution of the disease, even after cardiac surgery.

Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical Revascularization: Results From the STICH Trial (Surgical Treatment for Ischemic Heart Failure).

BACKGROUND: Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular dysfunction enrolled in the prospective STICH trial (Surgical Treatment for Ischemic Heart Failure Study). METHODS: The STICH trial randomized 1212 patients (148 [12%] women and 1064 [88%] men) with coronary artery disease and left ventricular ejection fraction ≤35% to CABG+medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex. RESULTS: At baseline, women were older (63.4 versus 59.3 years; P=0.016) with higher body mass index (27.9 versus 26.7 kg/m2; P=0.001). Women had more coronary artery disease risk factors (diabetes mellitus, 55.4% versus 37.2%; hypertension, 70.9% versus 58.6%; hyperlipidemia, 70.3% versus 58.9%) except for smoking (13.5% versus 21.8%) and had lower rates of prior CABG (0% versus 3.4%; all P<0.05) than men. Moreover, women had higher New York Heart Association class (class III/IV, 66.2% versus 57.0%), lower 6-minute walk capacity (300 versus 350 m), and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (51 versus 63; all P<0.05). Over 10 years of follow-up, all-cause mortality (49.0% versus 65.8%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.52-0.86; P=0.002) and cardiovascular mortality (34.3% versus 52.3%; adjusted hazard ratio, 0.65; 95% confidence interval, 0.48-0.89; P=0.006) were significantly lower in women compared with men. With randomization to CABG+MED versus MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, cardiovascular mortality, or the composite of all-cause mortality or cardiovascular hospitalization (all P>0.05). In addition, surgical deaths were not statistically different (1.5% versus 5.1%; P=0.187) between sexes among patients randomized to CABG per protocol as initial treatment. CONCLUSIONS: Sex is not associated with the effect of CABG+MED versus MED on all-cause mortality, cardiovascular mortality, the composite of death or cardiovascular hospitalization, or surgical deaths in patients with ischemic left ventricular dysfunction. Thus, sex should not influence treatment decisions about CABG in these patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595.

CABG in patients with left ventricular dysfunction: indications, techniques and outcomes.

Ischemic chronic heart failure (CHF) represents one of the cardiovascular diseases with the worst degree of morbidity and mortality in the western world, and with the highest health care costs. Despite several studies demonstrated that surgical revascularization (CABG), especially in the presence of viable myocardium, improve heart function, and therefore, survival, the matter remains unclear and controversial. In the late 1970s, the Coronary Artery Surgery Study showed that a subgroup of patients with coronary artery disease, angina, and reduce LV function had a significant survival benefit after CABG compared to those treated medically. The key concept behind this observation was the presence of viable myocardium, which can resume function following revascularization. In contrary, the surgical treatment for ischemic heart failure (STICH) trial, which randomized patients with CAD and LV dysfunction to evidence-based medical therapy or CABG plus medical therapy, failed to demonstrate at a median follow-up of 56 months a significant difference between the CABG group and the medical therapy group in the rate of death from any cause. However, the results of the STICH extension study (STICHES) at 10 years follow-up demonstrated that CABG is associated with a significant reduction in all-cause mortality, cardiovascular mortality, and readmission for heart compared to optimal medical therapy (OMT) in patients with severe ischemic LV dysfunction. Therefore, this review discusses the available evidences in literature, from observational studies to randomized trials, including operative techniques and controversial issues, in order to better clarify the role of CABG in the current management of ischemic patients with LVD.

Long-term results of suture annuloplasty for degenerative mitral valve disease: a propensity-matched analysis.

AIMS: Ring annuloplasty is the gold standard of surgical repair in degenerative mitral valve disease. However, prosthetic annuloplasty has some drawbacks and potential hazards. Suture annuloplasty theoretically is able to preserve annular leaflet dynamics and left ventricular performance, but experience is limited. The aim of the study was to review the early and long-term outcome of the posterior double-suture annuloplasty (DSA) technique for degenerative mitral valve repair. METHODS: From January 2002 to December 2008, 400 patients underwent primary mitral valve repair for degenerative disease either with posterior DSA [n = 147 (37%)] or with flexible posterior annuloplasty band [n = 253 (63%)]. Differences in patient characteristics were addressed by propensity-score matching (132 pairs). A composite end-point of mitral valve failure (MVF) was calculated as the incidence of mitral valve regurgitation greater than 2+ or need for mitral valve replacement at follow-up. RESULTS: After propensity-score matching, the distribution of preoperative variables among matched pairs was, on average, equal. Isolated annuloplasty and leaflet repair techniques were similarly performed in both groups (P = 0.20). In-hospital mortality was comparable between the two study groups (P = 0.48). Predischarge echocardiography showed excellent results regarding valve hemodynamics (P = 0.71). At a mean follow-up of 11 ±â€Š3 years, all-cause mortality (P = 0.12), need for mitral valve replacement (P = 0.49), and cardiac re-hospitalization rate (P = 0.57) resulted comparable between the two groups. Ten-year survival (75 vs. 71%, P = 0.51) and freedom from MVF (92 vs. 84%, P = 0.39) were similar between posterior annuloplasty band and DSA groups. CONCLUSION: Suture annuloplasty demonstrated comparable results with posterior flexible band repair and could be a viable option for mitral valve surgery in selected patients, such as in the minimally invasive approach, in endocarditis, and in developing countries.

Myocardial scar location as detected by cardiac magnetic resonance is associated with the outcome in heart failure patients undergoing surgical ventricular reconstruction.

OBJECTIVES: Post-infarction myocardial scar causes adverse left ventricular remodelling and negatively affects the prognosis. We sought to investigate whether scar extent and location obtained by cardiac magnetic resonance may affect the reverse remodelling and survival of heart failure patients undergoing surgical ventricular reconstruction. METHODS: From January 2011 to December 2015, 151 consecutive patients with previous myocardial infarction and left ventricular remodelling underwent surgical ventricular reconstruction at our Institution, of which 88 (58%) patients had a preoperative protocol-standardized late gadolinium enhancement (LGE)-cardiac magnetic resonance examination during the week before surgery. We excluded 40 patients with devices (26%), 15 patients with irregular heart rhythm (permanent atrial fibrillation, 10% not included in the device group) or mixed contraindications (severe claustrophobia or presence of material magnetic resonance not compatible). Among the 145 survivors, 11 patients received an implantable cardioverter defibrillator after surgery (mostly for persistent low ejection fraction) and were excluded as well, yielding a total of 59 patients (48 men, aged 65 ± 9 years) who repeated a protocol-standardized LGE-cardiac magnetic resonance examination even 6 months postoperatively and therefore represent the study population. Patients were grouped according to the presence of LGE in the antero-basal left ventricular segments (Group A) or the absence of LGE in the same segments (Group B). The postoperative left ventricular end-systolic volume index was considered the primary end-point. RESULTS: After surgery, left ventricular end-systolic volume index and end-diastolic volume index significantly decreased (P < 0.001, for both), while diastolic sphericity index and ejection fraction significantly increased (P = 0.015 and P < 0.001, respectively). The presence of LGE in the antero-basal left ventricular segments (10 patients, Group A) was the only independent predictor of outcome (P = 0.02) at multivariate analysis, being the postoperative left ventricular end-systolic volume index significantly higher compared to that of patients of Group B (49 patients) (78 ± 26 ml/m2 vs 55 ± 20 ml/m2, P = 0.003). Furthermore, patients with a postoperative left ventricular end-systolic volume index >60 ml/m2 showed a higher risk of cardiac events (hazard ratio = 3.67, P = 0.02). CONCLUSIONS: In patients undergoing surgical ventricular reconstruction, LGE scar location affects the left ventricular reverse remodelling, which in turn might limit the survival benefit.