Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation - The NOVA Study.

BACKGROUND: Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in two clinical studies of cardiac surgery patients, without new safety observations. METHODS: The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety. CONCLUSIONS: The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

Relationships between mitral annular calcification and cardiovascular events: A meta-analysis.

BACKGROUND: Mitral annular calcification (MAC) is prevalent in the aging population, with recent renewed interest regarding its associations with cardiovascular risk factors, outcomes, and influence on valvular heart disease and interventions. This meta-analysis aimed to report the relationships between MAC and cardiovascular mortality and morbidity events. METHODS: Relevant studies were searched from PubMed, Cochrane, and Embase databases until November 30, 2019. Associations between MAC as a binary variable with death and cardiovascular events were pooled using random-effects models. The main outcomes of interest were all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, atrial fibrillation, and procedural outcomes. RESULTS: Among 799 article abstracts and 122 full-text articles screened, 26 (16 prospective and 10 retrospective) studies totaling 35 070 subjects were analyzed. MAC was associated with higher all-cause death, hazard ratio (95% confidence interval) 1.76 (1.43-2.22), and cardiovascular mortality 1.85 (1.45-23.5). It also positively correlated with myocardial infarction 1.48 (1.22-1.79), stroke 1.51 (1.22-2.05), incidental heart failure 1.55 (1.30-1.84), atrial fibrillation 1.75 (1.43-2.15), and their composite, major adverse cardiovascular events (MACE). Finally, conversion to mitral valve replacement at time of cardiac surgery was more in patients with MAC than without MAC, with odds ratio (95% confidence interval) 2.82 (1.28-6.18). CONCLUSION: Mitral annular calcification was overall associated with higher rates of death, and both individual and composite cardiovascular events. The presence of increasingly encountered MAC has significant clinical implications for cardiovascular risk assessment and valvular interventions.

Differences in patterns of progression of secondary mitral regurgitation.

AIMS: Little data exist about the natural history and disease progression of secondary mitral regurgitation (SMR). We sought to study the temporal progression of left-sided volumes and functions in patients who progress to develop severe SMR. METHODS AND RESULTS: We screened patients with chronic severe SMR who had at least one previous transthoracic echocardiography showing non-severe MR. Unsupervised phenotypic clustering based on baseline and rate of change in left ventricular (LV) and left atrial (LA) volumes, ejection fraction (EF), and MR severity progression identified two different phenotypes. We then compared them in terms of clinical characteristics, mechanistic and anatomical features, management, and outcomes. A total of 257 patients were included. Cluster 1 started with lower EF and LA strain and higher LV and LA volumes compared with Cluster 2, with a slower progression into severe SMR. At the onset of severe MR, Cluster 2 still had higher EF, lower LV volumes, but similar LA volumes and strain, and less proportionate SMR, compared with Cluster 1. They also had higher tenting height and more compensatory leaflet growth. On follow-up, Cluster 1 had more ventricular-directed therapies, whereas Cluster 2 received more mitral valve interventions. While the heart failure burden was higher in Cluster 1, there was no difference in mortality rates. CONCLUSION: Based on disease progression, two distinct progression patterns of SMR exist, having different anatomical and mechanistic features with variation in management and outcomes.

Severe Atrial Functional Mitral Regurgitation: Clinical and Echocardiographic Characteristics, Management and Outcomes.

OBJECTIVES: This study was designed to compare the clinical and echocardiographic characteristics, management, and outcomes of severe atrial functional mitral regurgitation (AFMR) to primary mitral regurgitation (PMR). BACKGROUND: AFMR remains poorly defined clinically. METHODS: Consecutive patients who underwent transesophageal echocardiography at our institution between 2011 and 2018 for severe mitral regurgitation with preserved left ventricular function were screened. We excluded patients with endocarditis, any form of cardiomyopathy, or prior mitral intervention. The absence of leaflet pathology defined AFMR. Outcomes included death and heart failure hospitalizations. RESULTS: A total of 283 patients were included (AFMR = 14%, PMR = 86%). Compared to PMR, patients with AFMR had more comorbidities, including hypertension (94.9% vs. 76.2%; p = 0.015), diabetes mellitus (46.2% vs. 18.4%; p < 0.001), long-standing atrial fibrillation (28.2% vs. 13.1%; p = 0.015), prior nonmitral cardiac surgery (25.6% vs. 9.8%; p = 0.004), and pacemaker placement (33.3% vs. 13.5%; p = 0.002). They also had higher average E/e' (median [interquartile range]:16.04 [13.1 to 22.46] vs. 14.1 [10.89 to 19]; p = 0.036) and worse longitudinal left atrial strain peak positive value (16.86 ± 12.15% vs. 23.67 ± 14.09%; p = 0.002) compared to PMR. During follow-up (median: 22 months), patients with AFMR had worse survival (log-rank p = 0.009) and more heart failure hospitalizations (log-rank p = 0.002). They were also less likely to undergo mitral valve intervention (59.0% vs. 83.6%; p = 0.001), although surgery was associated with improved survival (log-rank p = 0.021). On multivariable regression analysis, AFMR was independently associated with mortality [adjusted odds ratio: 2.61, 95% confidence interval: 1.17 to 5.83; p = 0.02]. CONCLUSIONS: AFMR constitutes an under-recognized high-risk group, with significant comorbidities, limited therapeutic options, and poor outcomes.

Superior vena cava syndrome post minimally invasive mitral valve repair.

We describe an unusual presentation of cardiac tamponade as superior vena cava syndrome post minimally invasive mitral valve repair. The tamponade was caused by local compression of junction between the right atrium and superior vena cava. This case illustrates the importance of using transesophageal echocardiogram in postoperative management of cardiac surgery patients.

Sex-Based Differences in Outcomes After Mitral Valve Surgery for Severe Ischemic Mitral Regurgitation: From the Cardiothoracic Surgical Trials Network.

OBJECTIVES: This study investigated sex-based differences in outcomes after mitral valve (MV) surgery for severe ischemic mitral regurgitation (SIMR). BACKGROUND: Whether differences in outcomes exist between men and women after surgery for SIMR remains unknown. METHODS: Patients enrolled in a randomized trial comparing MV replacement versus MV repair for SIMR were included and followed for 2 years. Endpoints for this analysis included all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCE) (defined as the composite of death, stroke, hospitalization for heart failure, worsening New York Heart Association functional class or MV re-operation), quality of life (QOL), functional status, and percentage of change in left ventricular end-systolic volume index (LVESVI) from baseline through 2 years. RESULTS: Of 251 patients enrolled in the trial, 96 (38.2%) were women. Compared with men, women had smaller LV volumes and effective regurgitant orifice areas (EROA) but greater EROA/left ventricular (LV) end-diastolic volume ratios. At 2 years, women had higher rates of all-cause mortality (27.1% vs. 17.4%, respectively; adjusted hazard ratio [adjHR]: 1.85; 95% confidence interval [CI]: 1.05 to 3.26; p = 0.03) and of MACCE (49.0% vs. 38.1%, respectively; adjHR: 1.58; 95% CI: 1.06 to 2.37; p = 0.02). Women also reported worse QOL and functional status at 2 years. There were no significant differences in the percentage of change over 2 years in LVESVI between women and men (adjß: -10.4; 95% CI: -23.4 to 2.6; p = 0.12). CONCLUSIONS: Women with SIMR displayed different echocardiographic features and experienced higher mortality and worse QOL after MV surgery than men. There were no significant differences in the degree of reverse LV remodeling between sexes. (Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation [Severe Ischemic Mitral Regurgitation]; NCT00807040).

Atrial fibrillation after cardiac surgery: where are we now?

OBJECTIVE: To review: 1) Pathophysiology of postoperative atrial fibrillation (POAF); 2) Risk factors for POAF; 3) Prophylaxis of POAF; 4) Treatment of POAF; and 5) Future directions. METHODS: We searched the Medline database for articles published between January, 1966 to September, 2008. We used the following keywords: Atrial fibrillation, Postoperative atrial fibrillation, Coronary Artery Bypass, and antiarrhythmic agents. Additionally, we searched references from all relevant articles. CONCLUSIONS: POAF occurs in 25-60% of patients depending on the type of cardiac surgery performed. POAF generally occurs on postoperative day 2 or 3. POAF is associated with an increased risk of morbidity and mortality, and longer hospital stay. Prophylactic treatments reduce the likelihood of POAF. In patients who experience POAF, rhythm strategies should be used in those who are symptomatic and hemodynamically unstable. All other patients should be managed with rate strategies.

Geometric differences of the mitral apparatus between ischemic and dilated cardiomyopathy with significant mitral regurgitation: real-time three-dimensional echocardiography study.

BACKGROUND: This study was conducted to elucidate the geometric differences of the mitral apparatus in patients with significant mitral regurgitation caused by ischemic cardiomyopathy (ICM-MR) and by idiopathic dilated cardiomyopathy (DCM-MR) by use of real-time 3D echocardiography (RT3DE). METHODS AND RESULTS: Twenty-six patients with ICM-MR caused by posterior infarction, 18 patients with DCM-MR, and 8 control subjects were studied. With the 3D software, commissure-commissure plane and 3 perpendicular anteroposterior (AP) planes were generated for imaging the medial, central, and lateral sides of the mitral valve (MV) during mid systole. In 3 AP planes, the angles between the annular plane and each leaflet (anterior, Aalpha; posterior, Palpha) were measured. In ICM-MR, Aalpha measured in the medial and central planes was significantly larger than that in the lateral plane (39+/-5 degrees, 34+/-6 degrees, and 27+/-5 degrees, respectively; P<0.01), whereas Palpha showed no significant difference in any of the 3 AP planes (61+/-7 degrees, 57+/-7 degrees, and 56+/-7 degrees, P>0.05). In DCM-MR, both Aalpha (38+/-8 degrees, 37+/-9 degrees, and 36+/-7 degrees, P>0.05) and Palpha (59+/-6 degrees, 58+/-5 degrees, and 57+/-6 degrees, P>0.05) revealed no significant differences in the 3 planes. CONCLUSIONS: The pattern of MV deformation from the medial to the lateral side was asymmetrical in ICM-MR, whereas it was symmetrical in DCM-MR. RT3DE is a helpful tool for differentiating the geometry of the mitral apparatus between these 2 different types of functional mitral regurgitation.

Importance of ischemic and viable myocardium for patients with chronic ischemic mitral regurgitation and left ventricular dysfunction.

The objective of this investigation is to determine the importance of ischemic viable myocardium for clinical outcomes in patients with severe chronic ischemic mitral regurgitation and severe left ventricular dysfunction undergoing surgical correction of mitral regurgitation. The study included 54 patients with left ventricular ejection fraction of 27 +/- 9%. Positron emission tomography was performed preoperatively for the identification of ischemic viable myocardium. The patients with a large amount of ischemic viable myocardium (> or =5 segments) had significantly lower 6-month mortality rates than those with less viable myocardium (0 to 4 segments) after the surgery.

Surgical Treatment of Atrial Fibrillation.

Atrial fibrillation (AF) is now commonly treated at the time of valvular heart surgery or coronary artery bypass grafting. Surgical ablation of AF, which is predicated upon the Maze procedure, includes creation of lines of conduction block and excision of the left atrial appendage. A full bi-atrial lesion set is associated with success in 80% to 95% of patients and virtually eliminates the risk of late stroke. A complex but safe operation, the classic cut-and-sew Maze procedure has been applied by relatively few surgeons. However, recent advances in understanding of the pathogenesis of AF and development of new ablation technologies enable surgeons to perform pulmonary vein isolation, create linear left and right atrial lesions, and remove the left atrial appendage rapidly and safely. Lesions are created under direct vision, minimizing the risk of damage to the pulmonary veins and adjacent mediastinal structures. Recently developed instrumentation now enables thoracoscopic and keyhole approaches, facilitating extension of epicardial AF ablation and excision of the left atrial appendage to patients with isolated AF and no other indication for cardiac surgery. In addition, novel devices designed specifically for minimally invasive epicardial exclusion of the left atrial appendage will broaden the range of treatment options for patients with AF, possibly eliminating the need for anticoagulation in selected patients.

Geometric predictor of significant mitral regurgitation in patients with severe ischemic cardiomyopathy, undergoing Dor procedure: a real-time 3D echocardiographic study.

BACKGROUND AND PURPOSE: Significant mitral regurgitation (MR) is frequently associated with coronary artery disease. The precise geometric predictors of significant MR in ischemic cardiomyopathy are not clearly defined. We performed real-time 3D echocardiography (RT3DE) in 48 patients scheduled for infarct exclusion surgery or Dor procedure, 22 of whom had moderate or severe MR (DorMR) and 26 with no or trivial MR (DorNoMR). METHODS: Two orthogonal apical volumetric planes of LV, commissure-commissure (CC) and antero-posterior (AP) planes, were generated during mid-systole. Mitral valve tenting height (MVTht) and area (MVTa) were measured. The degree of leaflet tethering was estimated by the angles between the annular plane and each leaflet (anterior leaflet: Aalpha, posterior leaflet: Palpha). RESULTS: MVTht (1.11+/-0.14 vs 0.78+/-0.20 cm, P<0.01) and MVTa (1.30+/-0.34 vs 0.87+/-0.27 cm(2), P<0.01) were significantly larger in DorMR compared with DorNoMR. In DorMR, both Aalpha (38+/-6 vs 31+/-7 degrees , P<0.01) and Palpha (60+/-7 vs 41+/-8 degrees , P<0.01) significantly increased more than those in DorNoMR. Multiple logistic regression analysis found Palpha to be the most important geometric predictor of significant MR. MV tenting area was found to be the strongest determinant of MR severity in ischemic cardiomyopathy patients with significant MR by multivariate linear regression analysis. CONCLUSIONS: Detecting significant posterior leaflet tethering, the most important predictor of significant MR, and measuring MV tenting area, the strongest determinant of MR severity, using RT3DE may be helpful in decision making of additive surgical intervention for MR in patients with severe ischemic cardiomyopathy.

Minimally invasive aortic valve replacement.

Partial upper sternotomy results in excellent exposure and a safe conduct of a variety of operations on the aortic valve and ascending aorta. The sternotomy extends into the right fourth intercostal space and is performed through an 8-10 cm long skin incision. The pericardium is open in the midline and aorta and right atrium are cannulated directly. Aortic valve is exposed through the oblique aortotomy, after placement of retraction sutures to the commissures. The aortic valve is excised and annulus meticulously debrided. Aortic valve prosthesis is then inserted into the annulus using a pledgeted non-absorbable suture. The procedure is performed with the usual surgical instrumentation and can therefore be easily adopted. We discuss the indications, surgical technique and results of this technique.