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Recurrence of left ventricular (LV) remodeling after surgical ventricular reconstruction (SVR) for ischemic cardiomyopathy has been reported to be partially attributed to autophagy. We aimed to examine the effects of trehalose, an autophagy inducer, on the recurrence of LV remodeling after SVR. After SVR in rats with ICM, trehalose was orally administered. The changes in LV end-diastolic dimension (LVEDD) and fractional shortening (FS) were evaluated. The activation of myocardial autophagy was also estimated by autophagy markers: microtubule-associated light chain 3 II (LC3-II) and p62; the former usually increases and the latter decreases if autophagy is activated. Significant LV reverse remodeling was observed early after SVR. On the other hand, the 28th postoperative day SVR + trehalose was associated with smaller LVEDD and better FS than SVR alone (LVEDD, P = 0.043; FS, P < 0.01). LC3-II increased comparably in both groups, while p62 was significantly lower in the SVR + trehalose group than in the SVR alone group (P < 0.01). In conclusion, trehalose attenuated the recurrence of LV remodeling and changed autophagy markers after SVR in rats with ICM. Trehalose may be a candidate for adjuvant therapy to retain the effects of SVR., (© 2021. Springer Japan KK, part of Springer Nature.)

Autophagy is an intracellular pathway that degrades unnecessary proteins and organelles and provides energy substrates during cellular ischemic conditions. Although pharmacological myocardial preconditioning with an autophagy inducer has been reported to protect cells against ischemic reperfusion (I/R), the effects of preconditioning using naturally occurring substances are still unknown. We aimed to examine whether autophagic preconditioning with trehalose improves cardiac function after myocardial stunning by global ischemia in rats. Rat hearts were perfused by oxygenized Krebs Henseleit (KH) solution in Langendorff system. Ten rats were randomized into the following two groups according to the perfusates during the preconditioning: control (KH solution only, n = 5) and trehalose (KH + 2% trehalose, n = 5). After the 35-min preconditioning period and subsequent 20 min of global ischemia, the hearts were reperfused for 60 min. Cardiac function was assessed during the reperfusion. To evaluate autophagy, myocardial protein expression of microtubule-associated protein light chain 3 (LC3) II was evaluated by western blotting. During I/R, a systolic functional parameter, maximum dP/dt was significantly higher; meanwhile, coronary flow tended to be higher in the trehalose group than in the control group. Myocardial LC3-II expression after preconditioning was higher in the trehalose group than in the control group and decreased to the control level after I/R. In conclusion, in a rat model of global myocardial ischemia, trehalose preconditioning improved cardiac function during I/R. Further studies would be needed to identify the mechanism and effects of trehalose preconditioning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Transvalvular leakage (TVL) of a prosthetic heart valve is not negligible regurgitant flow in patients with critically low contractile function. Although the opening function of prosthetic valves has been reported, its closing function is not well understood. A man in his 70 s had a history of mitral valve replacement (MVR) with a Magna Mitral® valve for ischemic mitral valve regurgitation. He presented with dyspnea 2 years postoperatively. Echocardiography showed moderate TVL. The pulmonary capillary wedge pressure and cardiac index were 37 mmHg and 1.65 L/min/m 2 , respectively. Because we considered his TVL relevant, we performed re-do MVR with a mechanical valve and papillary muscle approximation and suspension ("papillary muscle tugging approximation"). His cardiac function improved postoperatively; he was discharged with New York Heart Association class I. For MVR in patients with critically low contractile function, prosthetic valves, such as mechanical valves, with small TVL are recommended.

Background: The indications of left-ventricular plication (LVP) are controversial, although several studies have reported favorable outcomes in heart failure patients. The aim of this study was to assess left-ventricular (LV) wall stress and myocardial remodeling after LVP in a rat model of myocardial infarction (MI)., Methods: Sixteen rats underwent LVP by excluding the LV anterior wall scar 4 weeks after ligation of the left anterior descending artery. After 4 weeks, LV wall stress was assessed using transthoracic echocardiography and an LV catheter. Gene expression of the wall stress markers, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), were evaluated via reverse transcription polymerase chain reaction. Cardiomyocyte area and myocardial fibrosis were also examined through histological examinations. These parameters were compared to those in 16 rats that underwent coronary artery ligation but not LVP., Results: We noted that the LV end-diastolic dimension was smaller (9.9 ± 0.3 vs. 11.2 ± 0.2 mm, p < 0.05) and fractional shortening was greater (25 ± 2 vs. 15 ± 1%, p < 0.05) in LVP rats than in sham rats. Moreover, systolic wall stress was lower in LVP rats (71 ± 7 vs. 111 ± 9 × 103 dyn/cm2, p < 0.05). Myocardial ANF and BNP expression levels were lower in LVP rats (2.6 ± 0.3 vs. 4.4 ± 0.5 and 1.0 ± 0.1 vs. 1.5 ± 0.2 arbitrary units, respectively; p < 0.05). Cardiomyocyte area was significantly decreased in LVP rats (556 ± 15 vs. 670 ± 28 μm2, p = 0.003) and was correlated with LV wall stress (r = 0.669, p = 0.002). The reduction in myocardial fibrosis after LVP was not significant., Conclusion: LVP reduced LV wall stress and cardiomyocyte hypertrophy in a rat model of MI., (© 2016 S. Karger AG, Basel.)

Background: Since reduction annuloplasty alone for ischemic mitral regurgitation (MR) cannot prevent late recurrence of MR or improve survival for those with left ventricular (LV) dysfunction, and the surgical approach to this etiology is still controversial, we conducted a study to assess the efficacy of the additional papillary muscle approximation (PMA) procedure for ischemic MR by comparing the different subtypes of PMA., Methods: We studied 45 patients who underwent mitral annuloplasty and papillary muscle approximation (PMA) for ischemic MR between 2003 and 2012. Papillary muscles were approximated entirely (cPMA: complete PMA, n = 32) through an LV incision or partially from the tips to mid-parts (iPMA: incomplete PMA, n = 13) through the mitral and aortic valves. Twenty-three patients with cPMA also underwent LV plasty (LVP). We assessed the outcomes after PMA by comparing cPMA and iPMA., Results: The baseline MR grade, NYHA class, LV end-diastolic diameter, and LV ejection fraction (LVEF) were 2.8 ± 1.0, 3.2 ± 0.6, 67 ± 6 mm, and 30 ± 10%, respectively. There were no significant differences in these parameters among those with iPMA, cPMA/LVP-, and cPMA/LVP+, though iPMA patients had better LVEF than others. Three patients died before discharge and 12 died during the follow-up. Recurrence of grade 2+ and 3+ MR occurred in 8 and 2 patients, respectively. Reoperation for recurrent MR was performed only for the 2 patients with recurrence of grade 3+ MR. The cPMA was associated with lower mortality (log-rank P = 0.020) and a lower rate of recurrence of MR ≥2+ (log-rank P = 0.005) than iPMA. In contrast, there were no significant differences in the mortality (log-rank P = 0.45) and rate of recurrence (log-rank P = 0.98) between those with cPMA/LVP- and cPMA/LVP+. The 4-year survival rate and rate of freedom from recurrence of MR ≥2+ were 83% and 85% for those with cPMA, repectively. In contrast, the rates were 48% and 48% for those with iPMA, respectively., Conclusions: Complete PMA could be associated with lower postoperative mortality and higher durability of mitral valve repair for ischemic MR.

Objectives: Surgical ventricular reconstruction has been believed to be beneficial for those with ischemic cardiomyopathy. However, the effectiveness of surgical ventricular reconstruction was not proved by a large-scale trial, and no report has clearly demonstrated the exact indications and limitations of surgical ventricular reconstruction. The purpose of this study was to elucidate predictive factors of mortality after surgical ventricular reconstruction and to develop a prognostic model by calculating risk scores., Methods: The study subjects were 596 patients who underwent surgical ventricular reconstruction for chronic ischemic heart failure in 11 Japanese cardiovascular hospitals between 2000 and 2010. Potential predictors of postoperative mortality were assessed using the Cox proportional hazards model, and a risk score was calculated., Results: Forty-one patients died before discharge, and 81 patients died during a mean follow-up time of 2.9 years. Four independent predictors of mortality were identified: age, Interagency Registry for Mechanically Assisted Circulatory Support profile, left ventricular ejection fraction, and severity of mitral regurgitation. Each variable was assigned a number of points proportional to its regression coefficient. A risk score was calculated using the point scores for each patient, and 3 risk groups were developed: a low-risk group (0-4 points), an intermediate-risk group (5-6 points), and a high-risk group (7-12 points). Their 3-year survivals were 93%, 81%, and 44%, respectively (log-rank P < .001). Harrell's C-index of the predictive model was 0.69., Conclusions: A simple prognostic model was developed to predict mortality after surgical ventricular reconstruction. It can be useful in clinical practice to select treatment options for ischemic heart failure., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: Surgical ventricular reconstruction (SVR) for patients with severe left ventricular (LV) remodelling due to ischaemic cardiomyopathy is still controversial, because the Surgical Treatment for Ischaemic Heart Failure (STICH) trial demonstrated that SVR not only has no beneficial effect on survival compared with coronary artery bypass grafting (CABG) alone, but also is worse for those with a larger LV. Therefore, we assessed the impact of LV remodelling on the outcomes after SVR for ischaemic cardiomyopathy in Japan, using Di Donato's LV shape classification., Methods: From 2000 to 2010, 627 patients underwent SVR for ischaemic heart failure in 11 Japanese hospitals. To assess the patients with an LV ejection fraction (LVEF) of ≤ 35% like the STICH trial, considering the severity of LV remodelling, the patients with a preoperative LVEF of >35%, no preoperative LV volume assessment and no preoperative LV shape classification were excluded. Finally, 323 patients were selected as the study subjects. The LV shape was divided into three types according to Di Donato's classification. Types 1 and 3 indicate the aneurysmal and globally akinetic LV, respectively. Type 2 is the intermediate shape., Results: Type 1, 2 and 3 LV shapes were observed in 85 (26%), 104 (32%) and 134 (42%) of the patients, respectively. The preoperative LV volume and diameter increased if the LV became more akinetic (Type 3 > 2 > 1, P < 0.001). LVEF was lower in those with more akinetic LV (P = 0.002). The preoperative LV end-diastolic volume index and LVEF in Type 3 patients were 133 ± 47 ml/m(2) and 22 ± 7%, respectively. Mitral valve repair was more frequently performed for patients with the Type 3 LV shape (65%) than for the others (P < 0.001). The hospital mortality rates were 2.4, 2.9 and 7.4% for Type 1, 2 and 3 patients, respectively (P = 0.16). Kaplan-Meier analysis demonstrated no significant difference in mortality among the three groups (log-rank P = 0.37). The 5-year survival rates were 81, 70 and 73% for Type 1, 2 and 3 patients, respectively., Conclusions: The severity of LV remodelling did not affect survival after SVR plus CABG. The results of SVR were acceptable even for those with globally akinetic LV due to ischaemic cardiomyopathy.

Background: This study aimed to elucidate whether regional left ventricular wall thickening (LVWT) determined by quantitative gated SPECT (QGS) is useful in predicting surgical outcomes for ischemic (ICM) and nonischemic cardiomyopathy (NICM)., Methods and Results: The study group comprised 53 patients with either ICM (n=30, left ventricular ejection fraction (LVEF)=24.7±7.1%) or NICM (n=23, LVEF=24.0±6.3%) scheduled for surgical repair underwent preoperative QGS to evaluate regional LV function. LVWT of 20 segments derived from QGS was normalized by being divided by the normal value of each LV level. Normalized values of the segments were summed to be representative of each area. For 16 of the 30 patients with ICM and 17 of the 23 patients with NICM, surgical ventricular restoration and papillary muscle approximation (PMA) were performed for surgical repair and, for the rest, PMA alone was done for both ICM and NICM patients. Adjunctive coronary artery bypass grafting for ICM patients was added when necessary. Mean follow-up periods were 2.5±1.8 years for ICM and 2.2±2.4 years for NICM. Posterior regional LVWT in NICM (normalized sum value <0.61 n=7, ROC: AUC=0.80) predicted cardiac events (chronic heart failure and cardiac-caused death). The one-year cardiac event-free rates were 22.2% and 85.1% and the 2 years rates were 11.1% and 48.6% for the lower posterior WT group and higher posterior WT group respectively (P=0.003)., Conclusions: Posterior LVWT can be a predictor for postoperative cardiac events in patients with NICM.

Objectives: The aim of this study was to investigate the effects of surgical ventricular reconstruction (SVR) on cardiac efficiency as a surrogate marker for cardiac function and oxidative metabolism in patients with severe heart failure., Background: Our new integrated overlapping left ventriculoplasty, modified SVR, combined with mitral complex reconstruction, reduce left ventricular (LV) volume associated with improvement of symptoms of heart failure., Methods: Twelve consecutive patients with end-stage heart failure due to nonischemic dilated cardiomyopathy (DCM) (n = 6) and ischemic dilated cardiomyopathy (ICM) (n = 6) who underwent SVR were studied. Myocardial oxidative metabolism per gram of tissue was estimated by monoexponential clearance of (11)C-acetate positron emission tomography (K(mono)). Forward stroke volume at the LV outflow tract was measured by echocardiography. Cardiac efficiency was estimated by the ratio of external work (stroke volume at the LV outflow tract index × systolic blood pressure × heart rate) to K(mono) before and 1 month after SVR., Results: After SVR, medians of New York Heart Association functional class significantly improved from 3 to 1.5 (p < 0.01) in both DCM and ICM patients. End-systolic and end-diastolic volume and LV mass significantly decreased in both groups. Stroke volume at the LV outflow tract increased from 43 ± 8 ml to 52 ± 11 ml (p = 0.028) in DCM patients, but not in ICM patients (49 ± 21 ml to 59 ± 26 ml, p = 0.12). K(mono) × LV mass, as an index of global LV oxidative metabolism, decreased in DCM patients (13.6 ± 1.9 g/min vs. 8.6 ± 1.5 g/min, p = 0.03) and ICM patients (12.0 ± 3.4 g/min vs. 9.2 ± 1.0 g/min, p = 0.06). As a result, cardiac efficiency increased in all patients with DCM (3.34 ± 0.46 × 10E6 vs. 4.74 ± 0.88 × 10E6 mm Hg·ml·min/m(2), p = 0.03) and in 5 of 6 patients with ICM (4.54 ± 1.66 × 10E6 vs. 5.99 ± 2.11 × 10E6 mm Hg·ml·min/m(2), p = 0.12)., Conclusions: Combined surgery with SVR and mitral complex reconstruction reduced LV volume in association with improvement of cardiac efficiency in patients with severe heart failure., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)