Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery.

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking. METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed. RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group. CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial.

BACKGROUND: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. METHODS: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. RESULTS: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). CONCLUSIONS: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Circumflex Coronary Artery Injury during Modern Mitral Valve Surgery-A Review of Current Concepts and Perspectives.

The devastating impact of a circumflex coronary artery (CX) injury during mitral valve (MV) surgery is well reported. Despite significant improvements in preoperative risk assessment, intraoperative diagnosis and perioperative treatment strategies of CX injury during MV surgery, recent reports re-emphasize the variability in presentation, the unpredictable mechanisms of injury and the conflicting evidence regarding perioperative management. The progressive transition from conventional sternotomy access to minimally invasive surgical and transcatheter (TC) interventions for MV disease are associated with significant learning curves and require additional single-shaft and robotic console suture manipulation skills with special attentiveness to the potential risk of CX injury. The introduction of hybrid theatres that facilitate single stage surgical and TC interventions also provides new intraoperative diagnostic and therapeutic options without transporting unstable patients for percutaneous coronary intervention (PCI) assessment. By utilizing a MeSH terms-based PubMed search, a total of 89 patients with CX injury that occurred during MV surgery was identified from 49 reports between 1967 and 2022. MV surgery was performed by conventional sternotomy (n = 76, 85.4%), endoscopic (n = 12, 13.4%) and robotic access (n = 1, 1.1%), with 35 injuries (39.3%) resulting in total CX occlusion. Rescue PCI was utilized in 40 patients (44.9%). This manuscript provides a systematic overview of all available historic and contemporary reports on CX injury during MV surgery, outlines recent refinements in CX injury mechanisms, describes current MV surgery associated CX injury prevention and diagnosis and treatment strategies and highlights important MV procedural aspects that may minimize the risk and consequences of CX injury.

Transcatheter Mitral Valve Replacement After Surgical Repair or Replacement: Comprehensive Midterm Evaluation of Valve-in-Valve and Valve-in-Ring Implantation From the VIVID Registry.

BACKGROUND: Mitral valve-in-valve (ViV) and valve-in-ring (ViR) are alternatives to surgical reoperation in patients with recurrent mitral valve failure after previous surgical valve repair or replacement. Our aim was to perform a large-scale analysis examining midterm outcomes after mitral ViV and ViR. METHODS: Patients undergoing mitral ViV and ViR were enrolled in the Valve-in-Valve International Data Registry. Cases were performed between March 2006 and March 2020. Clinical endpoints are reported according to the Mitral Valve Academic Research Consortium (MVARC) definitions. Significant residual mitral stenosis (MS) was defined as mean gradient ≥10 mm Hg and significant residual mitral regurgitation (MR) as ≥ moderate. RESULTS: A total of 1079 patients (857 ViV, 222 ViR; mean age 73.5±12.5 years; 40.8% male) from 90 centers were included. Median STS-PROM score 8.6%; median clinical follow-up 492 days (interquartile range, 76-996); median echocardiographic follow-up for patients that survived 1 year was 772.5 days (interquartile range, 510-1211.75). Four-year Kaplan-Meier survival rate was 62.5% in ViV versus 49.5% for ViR (P<0.001). Mean gradient across the mitral valve postprocedure was 5.7±2.8 mm Hg (≥5 mm Hg; 61.4% of patients). Significant residual MS occurred in 8.2% of the ViV and 12.0% of the ViR patients (P=0.09). Significant residual MR was more common in ViR patients (16.6% versus 3.1%; P<0.001) and was associated with lower survival at 4 years (35.1% versus 61.6%; P=0.02). The rates of Mitral Valve Academic Research Consortium-defined device success were low for both procedures (39.4% total; 32.0% ViR versus 41.3% ViV; P=0.01), mostly related to having postprocedural mean gradient ≥5 mm Hg. Correlates for residual MS were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual MR was ViR. Significant residual MS (subhazard ratio, 4.67; 95% CI, 1.74-12.56; P=0.002) and significant residual MR (subhazard ratio, 7.88; 95% CI, 2.88-21.53; P<0.001) were both independently associated with repeat mitral valve replacement. CONCLUSIONS: Significant residual MS and/or MR were not infrequent after mitral ViV and ViR procedures and were both associated with a need for repeat valve replacement. Strategies to improve postprocedural hemodynamics in mitral ViV and ViR should be further explored.

Influence of fractional flow reserve on grafts patency: Systematic review and patient-level meta-analysis.

OBJECTIVE: To investigate the impact of invasive functional guidance for coronary artery bypass graft surgery (CABG) on graft failure. BACKGROUND: Data on the impact of fractional flow reserve (FFR) in guiding CABG are still limited. METHODS: Systematic review and individual patient data meta-analysis were performed. Primary objective was the risk of graft failure, stratified by FFR. Risk estimates are reported as odds ratios (ORs) derived from the aggregated data using random-effects models. Individual patient data were analyzed using mixed effect model to assess relationship between FFR and graft failure. This meta-analysis is registered in PROSPERO (CRD42020180444). RESULTS: Four prospective studies comprising 503 patients referred for CABG, with 1471 coronaries, assessed by FFR were included. Graft status was available for 1039 conduits at median of 12.0 [IQR 6.6; 12.0] months. Risk of graft failure was higher in vessels with preserved FFR (OR 5.74, 95% CI 1.71-19.29). Every 0.10 FFR units decrease in the coronaries was associated with 56% risk reduction of graft failure (OR 0.44, 95% CI 0.34 to 0.59). FFR cut-off to predict graft failure was 0.79. CONCLUSION: Surgical grafting of coronaries with functionally nonsignificant stenoses was associated with higher risk of graft failure.

Changes in surgical revascularization strategy after fractional flow reserve.

AIMS: In the randomized GRAFFITI trial, surgeons drew their strategy based on coronary angiography. When patients were randomized to fractional flow reserve (FFR)-guidance, surgeons were informed of the FFR values and asked to redraw their strategy. The aim of this study was to investigate the changes induced by FFR knowledge. METHODS AND RESULTS: The intended and performed strategy (before and after FFR) were compared. Among 172 patients, 84 with 300 lesions were randomized to the FFR-guided group. The intended strategy was to bypass 236 stenoses:108 with a venous and 128 with an arterial graft. After disclosing FFR, a change in strategy occurred in 64 lesions (21.3%) of 48 (55%) patients. Among 64 lesions for which the intended strategy was medical therapy, 16 (25%) were bypassed after disclosing FFR. The number of procedures with >1 venous graft planned was significantly reduced from 37 to 27 patients (p = .031). The proportion of on-pump surgery was significantly reduced from 71 to 61 patients (p = .006). The rates of clinical events at 1 year were similar between patients with or without at least one change in strategy. DISCUSSION: FFR-guided CABG is associated with a simplified surgical procedure in 55% of the patients, with similar clinical outcomes.

Fractional flow reserve in patients with reduced ejection fraction.

AIMS: Fractional flow reserve (FFR) has never been investigated in patients with reduced ejection fraction and associated coronary artery disease (CAD). We evaluated the impact of FFR on the management strategies of these patients and related outcomes. METHODS AND RESULTS: From 2002 to 2010, all consecutive patients with left ventricular ejection fraction (LVEF) ≤50% undergoing coronary angiography with ≥1 intermediate coronary stenosis [diameter stenosis (DS)% 50-70%] treated based on angiography (Angiography-guided group) or according to FFR (FFR-guided group) were screened for inclusion. In the FFR-guided group, 433 patients were matched with 866 contemporary patients of the Angiography-guided group. For outcome comparison, 617 control patients with LVEF >50% were included. After FFR, stenotic vessels per patient were significantly downgraded compared with the Angiography-guided group (1.43 ± 0.98 vs. 1.97 ± 0.84; P < 0.001). This was associated with lower revascularization rate (52% vs. 62%; P < 0.001) in the FFR-guided vs. the Angiography-guided group. All-cause death at 5 years of follow-up was significantly lower in the FFR-guided as compared with Angiography-guided group [22% vs. 31%. HR (95% CI) 0.64 (0.51-0.81); P < 0.001]. Similarly, rate of major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, revascularization, and stroke) was significantly lower in the FFR-guided group [40% vs. 46% in the Angiography-guided group. HR (95% CI) 0.81 (0.67-0.97); P = 0.019]. Higher rates of death and MACCE were observed in patients with reduced LVEF compared with the control cohort. CONCLUSIONS: In patients with reduced LVEF and CAD, FFR-guided revascularization was associated with lower rates of death and MACCE at 5 years as compared with the Angiography-guided strategy. This beneficial impact was observed in parallel with less coronary artery bypass grafting and more patients deferred to percutaneous coronary intervention or medical therapy.

Fractional flow reserve to guide and to assess coronary artery bypass grafting.

The aim of this review is to highlight the role of invasive functional evaluation in patients in whom coronary artery bypass graft (CABG) is indicated, and to examine the clinical evidence available in favour of fractional flow reserve (FFR) adoption in these patients, outline appropriate use, as well as point out potential pitfalls. FFR after CABG will also be reviewed, highlighting its correct interpretation and adoption when applied to both native coronary arteries and bypass grafts. Practice European guidelines support the use of FFR to complement coronary angiography with the highest degree of recommendation (Class IA) for the assessment of coronary stenosis before undertaking myocardial revascularization when previous non-invasive functional evaluation is unavailable or not conclusive. As a result, FFR has been adopted in routine clinical practice to guide clinicians decision as to whether or not perform a revascularization. Of note, due to the increasing confidence of the interventional cardiologists, FFR guidance is also being implemented to indicate or guide CABG. This is in anticipation of supportive clear-cut evidence, since recommendations for FFR adoption were based on randomized clinical trials investigating percutaneous coronary intervention (PCI) strategies in which patients with typical indications for CABG were excluded (e.g. left main disease, valvular disease, and coronary anatomy unsuitable for PCI). Based on the critical appraisal of the literature, FFR can play an important role in risk stratification and determining management strategy of patients either before or after CABG.

Endoscopic Port Access Surgery for Late Orthotopic Cardiac Transplantation Atrioventricular Valve Disease.

BACKGROUND: The study aim was to present details of the perioperative and long-term outcomes of redo-endoscopic port access surgery (REPAS) for late atrioventricular valve disease (AVVD) in orthotopic cardiac transplant (OCT) patients. METHODS: Between February 2004 and October 2015, REPAS was performed for late AVVD in seven consecutive OCT patients (mean age 57.9 ± 17.2 years; EuroSCORE II 21.2 ± 14.7%) at the authors' institution. The mean OCT-REPAS time interval was 7.8 ± 4.6 years (range: 1.3-13.8 years). NYHA class III or IV symptoms were present in four patients (57%). The mean left ventricular ejection fraction was 52.9 ± 3.9%, and surgical indications included severe mitral valve (MV) and tricuspid valve (TV) regurgitation in three patients (44%) and six patients (86%), respectively. Etiological factors included endomyocardial biopsy trauma (n = 6; 86%), degenerative disease (n = 2; 29%), and fungal endocarditis (n = 1; 14%). RESULTS: Procedures performed included MV repair (n = 3; 43%) and TV replacement (n = 3; 43%). There were no sternotomy conversions or revisions for any cause. The mean cardiopulmonary bypass and ischemic times were 178.4 ± 48.6 min and 118.3 ± 39.5 min, respectively. In-hospital morbidities included hospital-acquired pneumonia (n = 2; 29%). There were no wound infections or 30-day mortalities. The mean duration of hospitalization was 18.3 ± 11.0 days. A mean of 29.2 ± 45.6 patient-months (total 204.3 patient-months) was available for long-term clinical and echocardiographic analysis (n = 7; 100% complete). No MV or TV reinterventions were required. NYHA class ≤II was achieved in five patients (71%). No patient presented with residual MV regurgitation greater than grade I. CONCLUSIONS: REPAS for late AVVD in OCT patients is a safe and durable procedure with favorable technique-related mortality, in-hospital morbidity, and long-term cardiac-specific outcomes at experienced centers. The present technique provided an attractive benchmark against which emerging percutaneous interventions may be measured, and earlier referral of patients should be considered.

Rationale and design of the Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR trial): A randomized multicenter controlled event-driven trial.

Aortic valve replacement (AVR) therapy is an obvious choice for symptomatic severe aortic stenosis (AS) patients as it improves symptoms, left ventricular function, and survival. The treatment decisions and indication for AVR in asymptomatic patients with severe AS and normal left ventricular ejection fraction are less well established and the subject of ongoing debate. Many efforts have been made to define the best treatment option in asymptomatic AS patients with normal left ventricular ejection fraction. Retrospective and observational data imply that elective AVR for asymptomatic severe AS may lead to improvement in outcomes in comparison to surgery performed after onset of symptoms. The AVATAR trial will aim to assess outcomes among asymptomatic AS patients randomized to either elective early AVR or medical management with vigilant follow-up. In the latter group, AVR would be delayed until either the onset of symptoms or changes in predefined echocardiographic parameters. To the best of the authors' knowledge, it will be the first large prospective, randomized, controlled, multicenter clinical trial that will evaluate the safety and efficacy of elective AVR in this specific group of patients.

Fractional flow reserve-guided versus angiography-guided coronary artery bypass graft surgery.

BACKGROUND: Fractional flow reserve (FFR) is well established for patients undergoing percutaneous coronary intervention, yet little is known about candidates for coronary artery bypass graft surgery. METHODS AND RESULTS: From 2006 to 2010, we retrospectively included in this registry 627 consecutive patients treated by coronary artery bypass graft surgery having at least 1 angiographically intermediate stenosis. In 429 patients, coronary artery bypass graft surgery was based solely on angiography (angiography-guided group). In 198 patients, at least 1 intermediate stenosis was grafted with an FFR ≤0.80 or deferred with an FFR >0.80 (FFR-guided group). The end point was major adverse cardiovascular events at 3 years, defined as the composite of overall death, myocardial infarction, and target vessel revascularization. The rate of angiographic multivessel disease was similar in the angiography-guided and FFR-guided groups (404 [94.2%] versus 186 [93.9%]; P=0.722). In the FFR-guided group, this was significantly downgraded after FFR measurements to 86.4% (P<0.001 versus before FFR) and was associated with a smaller number of anastomoses (3 [2-3] versus 3 [2-4]; P<0.001) and rate of on-pump surgery (49% versus 69%; P<0.001). At 3 years, major adverse cardiovascular events were not different between the angiography-guided and FFR-guided groups (12% versus 11%; hazard ratio, 1.030; 95% confidence interval, 0.627-1.692; P=0.908). However, the FFR-guided group compared with the angiography-guided group presented a significantly lower rate of angina (Canadian Cardiovascular Society class II-IV, 31% versus 47%; P<0.001). CONCLUSIONS: FFR-guided coronary artery bypass graft surgery was associated with a lower number of graft anastomoses and a lower rate of on-pump surgery compared with angiography-guided coronary artery bypass graft surgery. This did not result in a higher event rate during up to 36 months of follow-up and was associated with a lower rate of angina.

Does a minimally invasive approach increase the incidence of patient-prosthesis mismatch in aortic valve replacement?

BACKGROUND AND AIM OF THE STUDY: The impact of a minimally invasive approach on patient-prosthesis mismatch (PPM) in patients undergoing aortic valve replacement (AVR) remains unknown. The study aim was to identify the impact of a minimally invasive approach for AVR on the incidence of PPM. METHODS: The results of a single-center experience in 506 patients who underwent isolated AVR through a minimally invasive or conventional sternotomy were analyzed. Postoperative PPM was defined as an effective orifice area index < 0.85 cm2/m2, and was correlated with surgical approach, mortality and cardiac events after surgery. RESULTS: Overall, postoperative PPM was present in 26.0% of the patients. The ratio of PPM was 24.1% in minimal access patients and 27.7% in conventional AVR patients (p = 0.35). Hospital mortality was similar in both groups (3.8% versus 3.4%, p = 0.62). The body mass index (BMI) was higher in patients with PPM (28.5 +/- 4.4 versus 25.3 +/- 3.6 kg/m2; p = 0.0001), but obesity was significantly associated with PPM (36.3% versus 9.4%; p = 0.0001). The PPM group included more patients with a left ventricular ejection fraction (LVEF) < 0.50 (12.8% versus 5.3%; p = 0.004). The independent risk factors for PPM were increased BMI (p = 0.0001), LVEF < 0.50 (p = 0.007) and preoperative aortic stenosis (p = 0.029). A LVEF < 0.50 increased the risk for PPM by 3.77-fold (95% CI: 1.4-9.9), while a high BMI increased the risk by 1.42-fold (95% CI: 1.3-1.5). Preoperative aortic insufficiency was associated with PPM, but did not significantly increase the risk. CONCLUSION: A minimally invasive approach for AVR did not lead to an increased incidence of PPM and associated adverse events following surgery.

Minimally Invasive Pectus Excavatum Correction and Endoscopic Port Access Mitral Valve Surgery.

This case study describes the successful short-term outcome of staged minimally invasive pectus excavatum correction and endoscopic mitral valve repair in a patient with severe mitral valve regurgitation and pectus excavatum.

Rationale and design of the ELEANOR trial early aortic valve surgery versus watchful waiting strategy in severe asymptomatic aortic regurgitation, ACRONYM: ELEANOR.

Background: The optimal treatment of patients with severe symptomatic aortic regurgitation (AR) is state-of-the-art surgery. Asymptomatic patients with advanced left ventricular (LV) dilatation and/or impaired ejection fraction should undergo surgical treatment, but there is no guidelines consensus on cut-off values for this recommendation. Multimodality imaging has brought new tools for the accurate selection of asymptomatic patients at risk of early clinical deterioration, however, prospective and randomized data are pending. Cardiac magnetic resonance (CMR)-derived AR quantification along with LV remodeling assessment appears to be the most accurate tool for a selection of such patients at risk. Trial design: The objective of our prospective and multicenter study is to determine whether patients at risk of early clinical deterioration as per CMR assessment will benefit from early surgical treatment. The study is designed as a superiority trial to demonstrate that early surgical treatment is safe and more effective than the standard treatment. A total of 217 asymptomatic patients with severe AR, but without current guidelines-based surgical indication, will be enrolled across all centers. We expect 24 % of patients identified as high clinical risk and therefore eligible for 1:1 randomization to early surgical treatment within 3 months or a watchful waiting strategy. Follow-up will be annual. We expect a complete restoration of LV size and function along with improved quality of life and physical performance in a short-term follow-up of 12 months. The primary endpoint will be a composite safety and efficacy with all criteria mandatory: 15 % or larger reduction of baseline CMR-derived LV end-diastolic volume index, LV ejection fraction >50 %, and no major adverse cardiovascular events. The annual follow-up will continue for a minimum of 4 years until the required number of endpoints is achieved to show a statistically significant difference in cardiovascular morbidity and mortality in early surgically treated patients. Conclusion: The ELEANOR trial is the first multicenter randomized controlled study to compare early surgical treatment with a watchful waiting strategy in asymptomatic patients with chronic severe AR at high risk of early clinical deterioration as per CMR assessment but without guidelines-based indications for surgical treatment.

Myocardial sodium-glucose cotransporter 2 expression and cardiac remodelling in patients with severe aortic stenosis: The BIO-AS study.

AIM: Cardiac remodelling plays a major role in the prognosis of patients with aortic stenosis (AS) and could impact the benefits of aortic valve replacement. Our study aimed to evaluate the expression of sodium-glucose cotransporter 2 (SGLT2) gene and protein in patients with severe AS stratified in high gradient (HG) and low flow-low gradient (LF-LG) AS and its association with cardiac functional impairments. METHODS AND RESULTS: Gene expression and protein levels of main biomarkers of cardiac fibrosis (galectin-3, sST2, serpin-4, procollagen type I amino-terminal peptide, procollagen type I carboxy-terminal propeptide, collagen, transforming growth factor [TGF]-ß), inflammation (growth differentiation factor-15, interleukin-6, nuclear factor-κB [NF-κB]), oxidative stress (superoxide dismutase 1 [SOD1] and 2 [SOD2]), and cardiac metabolism (sodium-hydrogen exchanger, peroxisome proliferator-activated receptor [PPAR]-α, PPAR-γ, glucose transporter 1 [GLUT1] and 4 [GLUT4]) were evaluated in blood samples and heart biopsies of 45 patients with AS. Our study showed SGLT2 gene and protein hyper-expression in patients with LF-LG AS, compared to controls and HG AS (p < 0.05). These differences remained significant even after adjusting for age, gender, body mass index, history of diabetes mellitus, arterial hypertension, and coronary artery disease. SGLT2 gene expression was positively correlated with: (i) TGF-ß (r = 0.72, p < 0.001) and collagen (r = 0.73, p < 0.001) as markers of fibrosis; (ii) NF-κB (r = 0.36, p < 0.01) and myocardial interleukin-6 (r = 0.68, p < 0.001) as markers of inflammation: (iii) SOD2 (r = -0.38, p < 0.006) as a marker of oxidative stress; (iv) GLUT4 (r = 0.33, p < 0.02) and PPAR-α (r = 0.36, p < 0.01) as markers of cardiac metabolism. CONCLUSION: In patients with LF-LG AS, SGLT2 gene and protein were hyper-expressed in cardiomyocytes and associated with myocardial fibrosis, inflammation, and oxidative stress.

Outcomes in patients with moderate and asymptomatic severe aortic stenosis followed up in heart valve clinics.

BACKGROUND: Heart valve clinics (HVC) have been introduced to manage patients with valvular heart disease within a multidisciplinary team. OBJECTIVE: To determine the outcome benefit of HVC approach compared with standard of care (SOC) for patients with moderate and asymptomatic severe aortic stenosis (mAS and asAS). METHODS: Single-centre, observational registry of patients with mAS and asAS with at least one cardiac ambulatory consultation at our Cardiovascular Centre. Based on the outpatient strategy, patients were divided into HVC group, if receiving at least one visit at HVC, and SOC group, if followed by routine cardiac consultations. RESULTS: 2129 patients with mAS and asAS were divided into those followed in HVC (n=251) versus SOC group (n=1878). The mean age was 76.5±12.4 years; 919 (43.2%) had asAS. During a follow-up of 4.8±1.8 years, 822 patients (38.6%) died, 307 (14.4%) were hospitalised for heart failure and 596 (28%) underwent aortic valve replacement (AVR). After propensity score matching, the number of consultations per year, exercise stress tests, brain natriuretic peptide (BNP) determinations and CTs were higher in the HVC cohort (p<0.05 for all). A shorter time between indication of AVR and less advanced New York Heart Association class was reported in the HVC cohort (p<0.001 and p=0.032). Compared with SOC, the HVC approach was associated with reduced all-cause mortality (HR=0.63, 95% CI 0.40 to 0.98, p=0.038) and cardiovascular death (p=0.030). At multivariable analysis, the HVC remained an independent predictor of all-cause mortality (HR=0.54, 95% CI 0.34 to 0.85, p=0.007). CONCLUSIONS: In patients with mAS and asAS, the HVC approach was associated with more efficient management and outcome benefit compared with SOC.

Global longitudinal strain and outcome after endoscopic mitral valve repair.

AIMS: Identification of heart failure (HF) patients with secondary mitral regurgitation (SMR) that benefit from mitral valve (MV) repair remains challenging. We have focused on the role of left ventricular global longitudinal strain (LV-GLS) and reservoir left atrial longitudinal strain (LASr) for the prediction of long-term survival and reverse remodelling in patients with SMR undergoing endoscopic MV repair. METHODS AND RESULTS: The study population consisted of 110 patients (age 67 ± 11 years, 66% men) with symptomatic SMR undergoing isolated MV repair using a minimally invasive surgical approach. Speckle tracking-derived LV-GLS and LASr were assessed in apical views using vendor-independent software. Over a median of 7.7 years (IQRs 2.9-11.2), 64 patients (58%) died. Significant reverse LV (↓ LVESVI >10 mL/m2 ), LA (↓ LAVI >10 mL/m2 ) remodelling or both were observed in 43 (39%), 37 (34%) and 19 (17%) patients, respectively. LV-GLS (HR 0.68, 95% CI 0.58-0.79, P < 0.001) and LASr (HR 0.93, 95% CI 0.88-0.97, P < 0.01) but not LV ejection fraction (LVEF) and LA volume index (LAVi) emerged as independent predictors of all-cause mortality in Cox regression analysis. LV-GLS was the only independent predictor of LV reverse remodelling (OR 1.24, 95% CI 1.05-1.43, P < 0.001) whereas LAVi and LASr were both independent predictors of LA reverse remodelling (both P < 0.05). In patients with atrial fibrillation at baseline, only LASr was an independent predictor (P < 0.05) of LA reverse remodelling. CONCLUSIONS: In patients with SMR undergoing endoscopic MV repair, LV-GLS and LASr are independently associated with long-term survival and reverse remodelling and may be helpful in selecting SMR patients who may benefit from this procedure.

Absolute coronary flow and microvascular resistance reserve in patients with severe aortic stenosis.

BACKGROUND: Development of left ventricle (LV) hypertrophy in aortic stenosis (AS) is accompanied by adaptive coronary flow regulation. We aimed to assess absolute coronary flow, microvascular resistance, coronary flow reverse (CFR) and microvascular resistance reserve (MRR) in patients with and without AS. METHODS: Absolute coronary flow and microvascular resistance were measured by continuous thermodilution in 29 patients with AS and 29 controls, without AS, matched for age, gender, diabetes and functional severity of epicardial coronary lesions. Myocardial work, total myocardial mass and left anterior descending artery (LAD)-specific mass were quantified by echocardiography and cardiac-CT. RESULTS: Patients with AS presented a significantly positive LV remodelling with lower global longitudinal strain and global work efficacy compared with controls. Total LV myocardial mass and LAD-specific myocardial mass were significantly higher in patients with AS (p=0.001). Compared with matched controls, absolute resting flow in the LAD was significantly higher in the AS cohort (p=0.009), resulting into lower CFR and MRR in the AS cohort compared with controls (p<0.005 for both). No differences were found in hyperaemic flow and resting and hyperaemic resistances. Hyperaemic myocardial perfusion (calculated as the ratio between the absolute coronary flow subtended to the LAD, expressed in mL/min/g), but not resting, was significantly lower in the AS group (p=0.035). CONCLUSIONS: In patients with severe AS and non-obstructive coronary artery disease, with the progression of LV hypertrophy, the compensatory mechanism of increased resting flow maintains adequate perfusion at rest, but not during hyperaemia. As a consequence, both CFR and MRR are significantly impaired.