New Technique for Aortic Valve Functional Annulus Reshaping Using a Handmade Prosthetic Ring

Background. Despite a wide development in aortic leaflets repair techniques, aortic valve annuloplastic procedures are still poorly investigated. We present our aortic valve annuloplastic system consisting of a handmade prosthetic ring with 2 components for reshaping the aortic annulus and sinotubular junction (STJ) and illustrates our surgical approach and clinical results. Methods. Since February 2003, 45 patients with aortic valve regurgitation underwent aortic annuloplasty using the new ring. Mean patient age was 58 16 years (range, 46 to 76 years). The ring has 2 components: a circular ring used to undersize the circumference of the aortoventricular junction and 3-crown-like shape ring used for STJ remodeling. The circular ring was sutured into the left ventricular outflow tract in the aortic subvalvular position and the STJ ring was sutured from the outside of the aortic root just at the level of the STJ. The 3 vertical bands of the STJ ring were fixed to the underlying circular ring to stabilize the continuity between the STJ and nadir of the aortic valve. Results. No in-hospital death occurred. Two patients had residual trivial aortic valve regurgitation postoperatively, and 3 patients required treatment for residual aortic regurgitation (more than mild). Mean length of the coaptation surface was 10 2 mm. The mean clinical follow-up (100% complete) was 22 16 months. All patients were free from cardiac and valve-related events, and no complications due to ring implantation occurred. Conclusions. This ring reshapes the functional aortic annulus and stabilizes all components of the native aortic valve stent to improve long-term results of valve repair

Treatment of pulmonary hypertension in patients undergoing cardiac surgery with cardiopulmonary bypass: a randomized, prospective, double-blind study.

OBJECTIVE: Pulmonary hypertension can already be present in patients undergoing cardiac surgery or can be exacerbated by cardiopulmonary bypass. Postoperative treatment is still a challenge for physicians. The aim of this study was to evaluate the effects of inhaled prostacyclin (iPGI2) and nitric oxide (iNO) compared with those of intravenous vasodilators. METHODS: This prospective, randomized, double-blind study included 58 patients affected by severe mitral valve stenosis and pulmonary hypertension with high pulmonary vascular resistance (> 250 dynes x s x cm(-5)) and a mean pulmonary artery pressure > 25 mmHg. All patients were monitored by central venous, radial arterial and Swan-Ganz catheters. Data were recorded at six different time points, before induction of anaesthesia, during and after surgery. Prostacyclin and nitric oxide were administered by inhalation 5 min before weaning from cardiopulmonary bypass and continued in the intensive care unit. Right ventricular function was evaluated by transoesophageal echocardiography. RESULTS: Hospital mortality was 3.4%. After drug administration, the mean pulmonary artery pressure and pulmonary vascular resistance were significantly decreased in the iNO and iPGI2 groups with respect to the baseline values (P < 0.05) and such a decrease was maintained throughout the study; this was not observed in the control group. In the iNO and iPGI2 groups we demonstrated a significant increase in cardiac indices and right ventricular ejection fraction after drug administration with respect to baseline. Furthermore, patients in the inhaled drug groups were weaned easily from cardiopulmonary bypass (P = 0.04) and had a shorter intubation time (P = 0.03) and intensive care unit stay (P = 0.02) than the control group. CONCLUSIONS: Our data suggest that both iNO and iPGI2 are effective in the treatment of pulmonary hypertension. iPGI2 has a number of advantages over iNO, including its easy administration and lower cost. Intravenous vasodilator treatment, on the other hand, is effective in terms of mortality but has a higher morbidity rate

The Role of MAPRE2 and Microtubules in Maintaining Normal Ventricular Conduction

BACKGROUND: Brugada syndrome is associated with loss-of-function SCN5A variants, yet these account for only ≈20% of cases. A recent genome-wide association study identified a novel locus within MAPRE2, which encodes EB2 (microtubule end-binding protein 2), implicating microtubule involvement in Brugada syndrome. METHODS: A mapre2 knockout zebrafish model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat–associated protein 9) and validated by Western blot. Larval hearts at 5 days post-fertilization were isolated for voltage mapping and immunocytochemistry. Adult fish hearts were used for ECG, patch clamping, and immunocytochemistry. Morpholinos were injected into embryos at 1-cell stage for knockdown experiments. A transgenic zebrafish line with cdh2 tandem fluorescent timer was used to study adherens junctions. Microtubule plus-end tracking and patch clamping were performed in human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) with MAPRE2 knockdown and knockout, respectively. RESULTS: Voltage mapping of mapre2 knockout hearts showed a decrease in ventricular maximum upstroke velocity of the action potential and conduction velocity, suggesting loss of cardiac voltage-gated sodium channel function. ECG showed QRS prolongation in adult knockout fish, and patch clamping showed decreased sodium current density in knockout ventricular myocytes and arrhythmias in knockout iPSC-CMs. Confocal imaging showed disorganized adherens junctions and mislocalization of mature Ncad (N-cadherin) with mapre2 loss of function, associated with a decrease of detyrosinated tubulin. MAPRE2 knockdown in iPSC-CMs led to an increase in microtubule growth velocity and distance, indicating changes in microtubule dynamics. Finally, knockdown of ttl encoding tubulin tyrosine ligase in mapre2 knockout larvae rescued tubulin detyrosination and ventricular maximum upstroke velocity of the action potential. CONCLUSIONS: Genetic ablation of mapre2 led to a decrease in voltage-gated sodium channel function, a hallmark of Brugada syndrome, associated with disruption of adherens junctions, decrease of detyrosinated tubulin as a marker of microtubule stability, and changes in microtubule dynamics. Restoration of the detyrosinated tubulin fraction with ttl knockdown led to rescue of voltage-gated sodium channel–related functional parameters in mapre2 knockout hearts. Taken together, our study implicates microtubule dynamics in the modulation of ventricular conduction

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Evolution Of Moderate Chronic Ischemic Mitral Regurgitation In Patients Underwent Only Coronary Artery Surgery: Clinical And Echocardiographic Follow-up At Rest And Under Exrecise

Management of moderate chronic ischemic mitral valve regurgitation (oIMR) is still debated. Several authors favouring surgical treatment in combining with coronary artery bypass grafting (CABG) while others suggested conservative approach. However, evolution of moderate oIMR after only CABG is still unclear. Aim of this study was to evaluate prospectively, at rest and under exercise condition, the clinical outcomes and echocardiographic results of patients with moderate cIMR underwent onlv CABG

POINT: Efficacy of adding mitral valve restrictive annuloplasty to coronary artery bypass grafting in patients with moderate ischemic mitral valve regurgitation: A randomized trial

Objective: Surgical management of moderate chronic ischemic mitral valve regurgitation is still debated. The aim of this study was to evaluate the effect of adding mitral valve repair to coronary artery bypass grafting on clinical outcomes and left ventricular remodeling in patients who underwent coronary artery bypass grafting alone versus coronary artery bypass grafting plus mitral valve repair in a randomized trial. Methods: Between February 2003 and May 2007, 102 patients were eligible for this study and were randomly assigned to one of 2 groups by means of card allocation: coronary artery bypass grafting plus mitral valve repair (CABG plus MVR group; 48 patients, 47%) or coronary artery bypass grafting alone (CABG group; 54 patients, 53%). The 2 groups were similar regarding demographics, perioperative clinical data, and outcomes. There were differences regarding cardiopulmonary bypass (P<.0001) and aortic crossclamp (P<.0001) times. Exercise tests were performed for all survivors to evaluate tolerance to exercise and variability on grade of mitral regurgitation and systolic pulmonary arterial pressure. The study was blinded for physicians and nurses involved in postoperative care and clinical follow-up. The mean follow-up was 32 18 months. Results: Overall in-hospital mortality was 3% (3 patients). One (1.8%) patient died in the CABG group, and 2 (4.1%) patients died in the CABG plus MVR group. Survival rates standard error at 5 years for patients in the CABG and CABG plus MVR groups were 88.8% 3.2% and 93.7% 3.1%, respectively. A significant difference was found between the 2 groups with regard to mean New York Heart Association class (P<.0001), left ventricular end-diastolic diameter (P<.01), left ventricular end-systolic diameter (P<.01), pulmonary arterial pressure (P<.0001), and left atrial size (P<.01). At follow-up, coronary artery bypass grafting alone was able to reduce mitral regurgitation grade in 40%of patients, whereas in the remaining patients mitral regurgitation grade remained stable or worsened. In the CABG group, among the 17 patients with mild mitral regurgitation and 12 patients with moderate mitral regurgitation at rest, 7 (40%) and 9 (75%) patients, respectively, had worsening in mitral regurgitation grade and pulmonary artery pressure during exercise. Conclusions: The efficacy of adding mitral valve repair to coronary artery bypass grafting is well demonstrated by the improvement of New York Heart Association functional class and percentage of left ventricular ejection fraction and by the decrease of mitral regurgitation grade, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, pulmonary artery pressure, and left atrial size. Moreover, coronary artery bypass grafting alone left more patients with heart failure symptoms at rest and during exercise. Combined coronary artery bypass grafting and mitral valve repair have no effect on survival at short-term follow-up, and the trends that are evident will likely become more significant with time