Restrictive annuloplasty or replacement on reverse remodeling for nonischemic dilated cardiomyopathy.

BACKGROUND: For patients with nonischemic dilated cardiomyopathy (NIDCM), the indications for and results of mitral surgery remain controversial. We reviewed a strategy of mitral repair and replacement for clinically relevant secondary mitral regurgitation (MR) in patients with NIDCM. METHODS: We retrospectively reviewed 65 patients with advanced NIDCM (LVEF < 40%) who underwent mitral surgery. Of them, 47 (72%) underwent mitral annuloplasty and 18 (28%) replacement for secondary MR. The primary endpoint was postoperative reduction in indexed LV end-systolic volume (LVESVI). RESULTS: At baseline, there was no intergroup difference in LVESVI (123 ± 47 vs. 147 ± 37 ml/m2, P = 0.055), LVEF (27 ± 8% vs. 25 ± 6%, P = 0.41), incidence of severe MR (57% (27/47) vs. 72% (13/18), P = 0.40), or EuroSCORE II score (6.2% vs. 7.6%, P = 0.90). At 6 months, the annuloplasty group reduced LVESVI to a greater degree than the replacement group (P < 0.001), yielding significantly smaller postoperative LVESVI (96 ± 59 vs. 154 ± 61 ml/m2, P < 0.001) and better LVEF (P < 0.001). The rates of moderate/severe recurrent MR were 17% (8/47) and 0%, respectively. Multivariable analysis demonstrated that mitral annuloplasty (OR 6.10, 95% CI 1.14-32.8, P = 0.035) was significantly associated with postoperative LV reverse remodeling. Cumulative survival was not different between the groups (P = 0.26). CONCLUSIONS: In patients with NIDCM, mitral annuloplasty reduced LV volume to a greater degree than did mitral replacement. These findings may assist with surgical options for secondary MR associated with NIDCM.

Safety confirmation of induced pluripotent stem cell-derived cardiomyocyte patch transplantation for ischemic cardiomyopathy: first three case reports.

Introduction: With the expected increase in patients with heart failure and ischemic 15 cardiomyopathy, the development of myocardial regenerative medicine using cell transplantation as a novel treatment method is progressing. This first-in-human clinical trial aimed to confirm the safety of cardiomyocyte patch transplantation derived from allogeneic induced pluripotent stem (iPS) cells based on the results of several preclinical studies. Study design: The inclusion criteria were left ventricular ejection fraction of 35% or less; heart failure symptoms of New York Heart Association class III or higher despite existing therapies such as revascularization; and a 1-year observation period that included a 3-month immunosuppressive drug administration period after transplantation of iPS cell-derived cardiomyocyte patches to evaluate adverse events, cardiac function, myocardial blood flow, heart failure symptoms, and immune response. Results: In the first three cases of this trial, no transplanted cell-related adverse events were observed during the 1-year observation period, and improvement in heart failure symptoms was observed. In addition, improvements in left ventricular contractility and myocardial blood flow were observed in two of the three patients. Regarding immune response, an increase in transplant cell-specific antibody titer was observed in all three patients after immunosuppressive drug administration. In one patient with poor improvement in cardiac function and myocardial blood flow, an increase in antibody titer against HLA-DQ was observed even before cell transplantation. Conclusions: Our case findings demonstrate that the transplantation of iPS cell-derived cardiomyocyte patches for ischemic cardiomyopathy can be safely performed; however, further investigation of the therapeutic effect and its relationship with an immune response is needed by accumulating the number of patients through continued clinical trials.

An operative case of pseudocoarctation with chronic dissection.

A 47-year-old man with a history of hypertension was found to have a prominent aortic knob on routine chest X-ray and was referred to our hospital. Enhanced computed tomography angiography showed severe flexion at the proximal descending aorta with chronic type B dissection localized to the flexion region. Graft replacement of the distal aortic arch was performed. Surgical management of chronic pseudocoarctation dissection is sparsely reported in the literature because of its rare occurrence. We present an operative case of a patient with chronic dissection of distal aortic arch pseudocoarctation.

Enhanced myocardial blood flow in ischemic cardiomyopathy by a slow-release synthetic prostacyclin agonist combined with coronary artery bypass grafting: The first human study in a Phase I/IIa clinical trial.

Background: YS-1402, which is a polymerized form of the synthetic prostacyclin agonist ONO-1301, has been proven in several preclinical studies to induce therapeutic effects for patients with ischemic cardiomyopathy (ICM). In this human study, we assessed the safety, tolerability, and efficacy of YS-1402, combined with coronary artery bypass grafting (CABG), for ICM. Methods: Twenty-four patients with ICM whose left ventricular ejection fraction was <40% with an indication for CABG were double-blindly assigned to four groups: placebo, 10-mg YS-1402, 30-mg YS-1402, and 100-mg YS-1402. YS-1402 or placebo medications were administered on the surface of the left ventricle at the time of the CABG. Pre- and postoperative cardiac function and myocardial blood flow were assessed for 6 months postoperatively, along with a safety assessment. Results: No severe adverse events were related to YS-1402. The maximum blood concentration of ONO-1301 was less than that of the no observable adverse effect level. Significantly increased myocardial blood flow (MBF) and cardiac function were observed in the YS-1402 group 26 weeks postoperatively, although no improvement in MBF occurred in the placebo group. Conclusion: This Phase I/IIa parallel group-controlled, dose-escalation study of YS-1402 combined with CABG for ICM demonstrated the safety, tolerability, and potential efficacy of YS-1402.

Left ventricle-mitral valve ring size mismatch following ring annuloplasty for nonischemic dilated cardiomyopathy.

BACKGROUND: In patients with ischemic mitral regurgitation (MR) undergoing restrictive mitral annuloplasty (RMA), the ratio of left ventricular (LV) end-systolic dimension (LVESD) to mitral valve (MV) ring size (ie, LV-MV ring mismatch) is associated with postoperative recurrent MR. However, the impact of LV-MV ring mismatch on postoperative recurrent MR, LV function recovery, and long-term survival in patients with nonischemic dilated cardiomyopathy (DCM) remains unknown. METHODS: Sixty-six patients with nonischemic DCM (mean LVESD, 62 mm) underwent RMA (mean ring size, 26 mm) between 2003 and 2014. Recurrent MR was defined as MR grade ≥2+ at a 6-month echocardiographic evaluation. RESULTS: At the 6-month follow-up, 23 patients (35%) had developed recurrent MR. In univariable logistic regression analysis, larger LVESD (P = .012) and LVESD/ring size ratio (P = .008) were associated with recurrent MR. In multivariable models adjusted for age, sex, baseline LV ejection fraction, and severe MR, only LVESD/ring size ratio (odds ratio, 4.65; 95% confidence interval, 1.04-25.0; P = .048) remained significantly associated with MR recurrence. Receiver operating characteristic curve analysis demonstrated an optimal cutoff value for the LVESD/ring size ratio of 2.42. Patients with an LVESD/ring size ratio >2.42 (n = 30; mismatch) had a lower 5-year cumulative survival rate compared with those with an LVESD/ring size ratio ≤2.42 (n = 36; nonmismatch) (52% vs 71%; P = .045). Postoperatively, LV dimensions were significantly reduced in both groups; however, improvements in LVEF were only modest in the mismatched group (P = .091). CONCLUSIONS: LV-MV ring size mismatch was associated with an increased risk of recurrent MR in our series. This finding may aid the formulation of surgical strategies for patients with nonischemic DCM.

Restrictive annuloplasty on remodeling and survival in patients with end-stage ischemic cardiomyopathy.

OBJECTIVES: To elucidate the influence of concomitant restrictive mitral annuloplasty (RMA) on postoperative left ventricular (LV) reverse remodeling and survival in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG). METHODS: This study comprised 157 patients with ischemic cardiomyopathy (LV ejection fraction ≤40%) who underwent CABG and completed echocardiographic examination at 1 year after surgery, with 84 (54%) undergoing concomitant RMA for clinically relevant ischemic mitral regurgitation. The primary end point was postoperative reduction in LV end-systolic volume index (LVESVI). The secondary end point was overall survival. Median follow-up was 5.1 years. RESULTS: At baseline, patients who underwent CABG with RMA had a larger LVESVI (83 ± 23 vs 75 ± 24 mm; P = .046). One-year postoperatively, CABG with RMA reduced the LVESVI more than did CABG alone (37% vs 21% from baseline; P < .001), yielding nearly identical postoperative LVESVI (53 ± 27 vs 61 ± 26 mm; P = .065). In multivariable logistic regression analysis, concomitant RMA was associated with significant LV reverse remodeling (odds ratio, 2.79; 95% CI, 1.34-5.78; P = .006). The prevalence in moderate or severe mitral regurgitation was not different between the groups (7% vs 10%; P = .58). Survival rates were similar between the groups (5 years, 78% vs 83%; P = .35). CONCLUSIONS: In patients with ischemic cardiomyopathy undergoing CABG, concomitant RMA was associated with significant reduction in LVESVI. The influence of LV reverse remodeling on survival remains undetermined.

Clinical Outcomes After Durable Mitral Valve Repair for Ischemic Mitral Regurgitation.

BACKGROUND: This study aimed to clarify the incidence and determinants of postoperative adverse events in patients with ischemic cardiomyopathy who achieved long-term durable mitral valve repair. METHODS: Between 1999 and 2015, 166 patients with chronic ischemic mitral regurgitation (MR) and a left ventricular ejection fraction ≤40% underwent restrictive mitral annuloplasty. During follow-up (65 ± 34 months), echocardiographic assessments were performed 809 times (mean, 4.9 ± 2.4 times), and 20 patients who had postoperative recurrent MR (moderate or severe) were excluded. Finally, 146 patients (aged 68 [63-75] years) whose MR was well controlled over time were included. RESULTS: A total of 61 deaths or 27 readmissions for heart failure were observed in 76 patients (52%). Among hospital survivors, age (adjusted hazard ratio, 1.05; P = .001) and estimated glomerular filtration rate (adjusted hazard ratio, 0.61; P = .001) were identified as independent predictors of long-term mortality or readmission for heart failure. The degree of postoperative left ventricular function recovery was comparable between patients with and without adverse events. However, the former group showed greater values for systolic pulmonary artery pressure, tricuspid regurgitation severity, inferior vena cava dimension, and plasma brain natriuretic peptide level throughout the follow-up period (group effect P < .05 for all). CONCLUSIONS: Approximately 50% of patients died or were hospitalized for heart failure even in the absence of recurrent MR during the 5-year follow-up, a finding indicating that durable mitral repair does not always lead to favorable clinical outcomes. The adverse events may have been related to volume overload secondary to impaired renal function and less favorable pulmonary hemodynamics.

Prediction of aortic valve regurgitation after continuous-flow left ventricular assist device implantation using artificial intelligence trained on acoustic spectra.

Significant aortic regurgitation (AR) is a common complication after continuous-flow left ventricular assist device (LVAD) implantation. Using machine-learning algorithms, this study was designed to examine valuable predictors obtained from LVAD sound and to provide models for identifying AR. During a 2-year follow-up period of 13 patients with Jarvik2000 LVAD, sound signals were serially obtained from the chest wall above the LVAD using an electronic stethoscope for 1 min at 40,000 Hz, and echocardiography was simultaneously performed to confirm the presence of AR. Among the 245 echocardiographic and acoustic data collected, we found 26 episodes of significant AR, which we categorized as "present"; the other 219 episodes were characterized as "none". Wavelet (time-frequency) analysis was applied to the LVAD sound and 19 feature vectors of instantaneous spectral components were extracted. Important variables for predicting AR were searched using an iterative forward selection method. Seventy-five percent of 245 episodes were randomly assigned as training data and the remaining as test data. Supervised machine learning for predicting concomitant AR involved an ensemble classifier and tenfold stratified cross-validation. Of the 19 features, the most useful variables for predicting concomitant AR were the amplitude of the first harmonic, LVAD rotational speed during intermittent low speed (ILS), and the variation in the amplitude during normal rotation and ILS. The predictive accuracy and area under the curve were 91% and 0.73, respectively. Machine learning, trained on the time-frequency acoustic spectra, provides a novel modality for detecting concomitant AR during follow-up after LVAD.

First Transcatheter Aortic Valve Implantation via Carotid Artery Performed in Japan.

Transcatheter aortic valve implantation (TAVI) through a peripheral arterial access is often complicated by concomitant arteriopathy. We describe here the first successful case of TAVI through the carotid artery in Japan. The patient was an 83-year-old woman with severe aortic stenosis (AS). Preoperative computed tomography (CT) revealed a shaggy distal aortic arch and left subclavian artery ostium, along with severely calcified bilateral iliofemoral arteries. Trans-apical and direct aortic approaches were abandoned because of frailty. Following the thorough cerebrovascular assessment, the left common carotid artery was selected for arterial access and a CoreValve transcatheter aortic valve was successfully implanted without neurologic complications.

Abnormalities of brain imaging in patients after left ventricular assist device support following explantation.

BACKGROUND: The potential impact of long-term left ventricular assist device (LVAD) support on the brain remains unclear. This study aimed to investigate cerebral microvascular damage in patients after long-term LVAD implantation using magnetic resonance imaging (MRI). METHODS: We reviewed the medical records of patients after continuous-flow LVAD implantation in our hospital from 2006 to 2016, who underwent brain MRI after LVAD explantation for either transplantation or recovery. Age- and sex-matched healthy controls and patients with chronic heart failure (CHF) were collected from our pooled MRI database. The presence of cerebral microbleeds (CMBs) and cortical superficial siderosis and the severity of white matter hyperintensity (WMH) and cerebral atrophy were compared between patients with prior LVAD and 2 control groups. RESULTS: This study included 49 patients with prior LVAD, 49 healthy controls, and 45 patients with CHF. CMBs and cortical superficial siderosis were detected in 98% (p < 0.001) and 31% (p < 0.001) of patients with prior LVAD, respectively. The number of CMBs was higher in patients with prior LVAD than in the 2 control groups. The severity of the WMH was higher in patients with prior LVAD than in healthy controls but similar to that in patients with CHF. Quantitative analyses of cerebral atrophy revealed a significantly higher bicaudate ratio and cella media index in patients with prior LVAD than in the 2 control groups. CONCLUSIONS: Patients after long-term LVAD support showed a higher prevalence of CMBs and cortical superficial siderosis and more severe cerebral atrophy than did controls. These findings may indicate cerebral microvascular damages in long-term LVAD support patients.

Staged open repair for a complex adult aortic coarctation.

We describe a two-stage open repair for a complex aortic coarctation in an adult. A total arch replacement with an elephant trunk was performed via a median sternotomy followed in 10 days by a replacement of the descending aorta through a left thoracotomy.

Restrictive Mitral Annuloplasty With or Without Papillary Muscle Approximation for Functional Mitral Regurgitation.

BACKGROUND AND AIM OF THE STUDY: The impact of adding papillary muscle approximation (PMA) to restrictive mitral annuloplasty (RMA) on postoperative left ventricular (LV) function is unknown. Changes in LV function parameters and clinical outcome were evaluated following RMA with and without PMA in patients with clinically relevant functional mitral regurgitation (FMR). METHODS: A total of 176 patients with advanced cardiomyopathy underwent RMA either with (n = 59) or without (n = 117) PMA. Propensity score analysis was used to adjust for group differences in several baseline characteristics, such as age, gender and LV ejection fraction (LVEF) (C-statistic = 0.80, goodness-of-fit value = 0.58). RESULTS: Serial echocardiography in 30 propensity score-matched pairs demonstrated decreases in LV end-systolic dimension (RMA alone: 57 ± 9 mm at baseline versus 54 ±11 mm at one month versus 56 ± 13 mm at latest examination; RMA + PMA: 56 ± 8 mm versus 53 ± 9 mm versus 48 ± 11 mm, respectively) and improvement in LVEF (RMA alone: 28 ± 8% versus 28 ± 11% versus 29 ± 10%; RMA + PMA: 30 ± 8% versus 30 ± 9% versus 36 ± 13%, respectively) in both groups. Greater degrees of changes in value were noted for patients receiving RMA + PMA (group effect p <0.05 for both). The two-year survival of both groups was similar (73 ± 8% versus 77 ± 23%, p = 0.7), but the RMA + PMA group showed a trend towards a greater freedom from composite events, defined as mortality and/or unscheduled heart failure re-admission (48 ± 9% versus 63 ± 9%, p = 0.1). CONCLUSIONS: RMA + PMA induced greater long-term effects on unloading of the left ventricle and improvements in LV systolic function than did RMA alone. PMA may be a useful adjunct repair in combination with RMA, although its clinical benefits remain to be determined.

The importance of hybrid stage I palliation for neonates with critical aortic stenosis and reduced left ventricular function.

The optimal management strategy for neonates with congenital aortic stenosis, two balanced ventricles, and duct-dependent systemic circulation (critical aortic stenosis) is still controversial. Thirteen patients with critical aortic stenosis underwent balloon aortic valvotomy (BAV) between 1996 and 2013, at the median age of 1 day old (range 0-28). Since 2010, bilateral pulmonary artery banding with ductal stenting following BAV was conducted for patients with reduced left ventricular (LV) function as a hybrid stage I palliation for the bridge to decision for further treatment. A follow-up was completed on all patients and the median follow-up period was 3.3 years (max 16.0). The overall survival rate at 15 years was 67.1 %. Six of the seven patients with maintained LV function could go on to the definitive Ross or Konno-aortic valve replacement at the median duration of 311 days after initial BAV, without any mortality. Three of four patients with reduced LV function died before 2010 with conventional treatment. With use of a hybrid stage I palliation, one of two patients ultimately underwent Fontan completion at 38 months of age and the other successfully underwent the definitive Ross-Konno operation at 9 months of age after recovery of the LV function. Although a statistically significant improvement has not been observed yet, the application of hybrid stage I palliation following BAV would be a favorable alternative for patients with reduced LV function to avoid a high-risk neonatal Ross or Norwood-type operation, and also to determine further treatment carefully.

Long-term outcomes of common atrioventricular valve plasty in patients with functional single ventricle.

OBJECTIVES: Common atrioventricular valve (CAVV) regurgitation is widely known as a risk factor for mortality and Fontan completion in patients with functional single ventricle. Hence, we reviewed our surgical experience with CAVV plasty in Fontan candidates. METHODS: Staged Fontan strategy and extracardiac total cavopulmonary connection as Fontan modification were our principal approaches in 1995. Since then, 38 consecutive Fontan candidates (21 males, median weight at operation was 7.0 kg and median age was 17 months old) underwent CAVV plasty. Right atrial isomerism was associated with 24 patients. The initial CAVV plasty was performed before inter-stage bidirectional Glenn (BDG) in 3 patients, at BDG in 23, before Fontan in 4 and during Fontan in 8. Since 1995, the modified Alfieri technique with a tailed, expanded, polytetrafluoroethylene tube as a bridging strip was the procedure for repair and 27 patients underwent the procedure. The mean follow-up period was 7.1 years (range 0-17 years). RESULTS: Actuarial survival and freedom from CAVV replacement rates at 1, 5 and 10 years were 81, 70 and 67% and 89, 85 and 75%, respectively. Seven patients ultimately underwent CAVV replacement with one death. Twenty-three of the 38 patients completed Fontan operation (61%). Association with total anomalous pulmonary venous connection (P= 0.01) and CAVV plasty before BDG (P= 0.05) were risk factors for mortality. CONCLUSIONS: CAVV plasty for patients with functional single ventricle is still challenging; however, the aggressive and repeated surgical intervention may contribute to provide better life-prognosis. The ventricular volume unloading effect of BDG without additional pulmonary blood flow or Fontan operation did not contribute to maintain CAVV function. Therefore, there would not be any hesitation for CAVV replacement to control CAVVR in the setting of systemic ventricular failure. Although the statistically significant therapeutic superiority of the modified Alfieri technique was not shown so far, further follow-up may reveal the advantage of this easy and simple technique.

Advancing cor triatriatum in Fontan circulation.

A 14-year-old female with mitral atresia, double outlet right ventricle, l-malposition of the great arteries, pulmonary valvular stenosis, bilateral superior vena cavae, and juxtaposed right atrial appendage had undergone a staged Fontan completion at 22 months of age. Ten years later, transthoracic echocardiography detected blood flow acceleration in the left atrium and scheduled follow-up cardiac catheterization revealed a 3.3 mm Hg pressure gradient between the common pulmonary venous chamber and left atrium, confirming cor triatriatum. An abnormal septum in the left atrium was surgically resected through a left-side right atriotomy. Postoperative echocardiography showed no accelerated blood flow in the left atrium.