Slope in preload recruitable stroke work relationship predicts survival after left ventriculoplasty and mitral repair in patients with idiopathic cardiomyopathy

AbstractBackgroundLeft ventriculoplasty (LVP) and mitral valve plasty (MVP) are sometimes effective for patients with idiopathic dilated cardiomyopathy (DCM) who are not eligible for heart transplantation. Strict patient selection is warranted for these controversial procedures.Methods and resultsThe subjects were 18 patients with idiopathic DCM and mitral regurgitation who had not been indicated for heart transplantation due to either older age or patient refusal, and who underwent LVP and MVP. Their mean age was 57±14 years and 50% were dependent on catecholamine infusion. The preload recruitable stroke work (PRSW) relationship and its slope (Mw) were estimated by a single-beat technique using transthoracic echocardiography. There were one 30-day mortality and six (33%) hospital deaths due to heart failure. The one-year survival rate was 50%. Left ventricular end-diastolic dimension (LVDd) decreased from 77±11 to 68±11mm (p=0.001) whereas the ejection fraction did not change. Preoperative Mw was significantly higher in one-year survivors than that in non-survivors (54±17ergcm−3103 vs. 31±10ergcm−3103, p=0.005). Preoperative LVDd was not different between the groups. The cut-off value of 42ergcm−3103 for Mw predicted one-year survival with high sensitivity (100%) and specificity (77%).ConclusionsMw, the slope in the PRSW relationship, may predict survival after LVP and MVP in patients with idiopathic DCM

Protective effects of trehalose preconditioning on cardiac and coronary endothelial function through eNOS signaling pathway in a rat model of ischemia-reperfusion injury

Coronary endothelial dysfunction is a major cause of ischemia-reperfusion (I/R) injury. Trehalose, a natural disaccharide, has been reported to ameliorate endothelial dysfunction during aging by activating endothelial nitric oxide synthase (eNOS); however, its role in I/R injury is unknown. This study evaluated the effects of trehalose preconditioning on cardiac and coronary endothelial function after I/R. Langendorff-perfused rat hearts underwent 30 min of global ischemia followed by 80 min of reperfusion with or without trehalose preconditioning. Rate pressure product (RPP) and coronary flow (CF) were measured during reperfusion. Perivascular edema was assessed by hematoxylin and eosin staining. Myocardial oxidative stress and apoptosis were evaluated by immunohistochemistry and TUNEL staining, respectively. eNOS dimerization was determined by western blotting. An eNOS inhibitor was used to examine the role of eNOS. Trehalose preconditioning showed a higher recovery rate after I/R as indicated by high RPP (control vs. trehalose, 28 +/- 6% vs. 46 +/- 9%; P = 0.017, Cohen's d = 2.3) and CF values (35 +/- 10% vs. 55 +/- 9%; P = 0.025, d = 1.7). Furthermore, trehalose preconditioning reduced perivascular edema, myocardial oxidative stress, and apoptosis. The eNOS dimerization ratio was increased by trehalose (1.2 +/- 0.2 vs. 1.6 +/- 0.2; P = 0.023, d = 2.1), which was associated with the recovery of RPP and CF. These effects of trehalose were abolished by the eNOS inhibitor. Trehalose preconditioning showed protective effects on cardiac and coronary endothelial function after I/R through the eNOS signaling pathway

Cardioprotective effects of chloroquine pretreatment on ischemic and reperfusion injury via activation of ERK1/2 in isolated rat hearts

Purpose Several therapeutic agents have been found to prevent myocardial ischemic and reperfusion (I/R) injury after cardiac surgery; however, no drug is routinely used to afford cardioprotective benefits in clinical settings. Herein, we aimed to determine whether chloroquine (CQ) pretreatment attenuates I/R injury after global ischemia in isolated rat hearts and elucidate mechanisms underlying the effects of CQ. Methods Isolated rat hearts were subjected to 30-min global ischemia, followed by 60-min reperfusion with Krebs-Henseleit buffer (KHB). Immediately before ischemia, 10 mL of pretreatment solutions (KHB, n = 4 or KHB + CQ [100 mu M], n = 4) were injected through the aortic root. Cardiac function was examined based on the rate pressure product (RPP). Myocardial apoptosis was evaluated using TUNEL staining. To assess the reperfusion ischemia salvage kinase pathway, protein expression levels of AKT and extracellular signal-regulated kinase (ERK1/2) were determined using western blotting. To investigate the role of ERK1/2, an ERK1/2 selective inhibitor was used in eight additional rats. Results The recovery rate of the RPP was higher in the KHB + CQ group than in the KHB group 60 min after I/R (KHB, 44 +/- 3% vs. KHB + CQ, 69 +/- 7%; P = 0.019, d = 2.2). CQ pretreatment reduced apoptosis and enhanced the phosphorylation of ERK1/2; however, AKT phosphorylation was unaltered. In addition, the ERK1/2 inhibitor abolished CQ-mediated cardioprotective effects. Conclusions CQ pretreatment showed protective effects on cardiac function after I/R by activating ERK1/2

Trehalose preconditioning for transient global myocardial ischemia in rats

Autophagy is an intracellular pathway that degrades unnecessary proteins and organelles and provides energy substrates during cellular ischemic conditions. Although pharmacological myocardial pre -conditioning 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) so-lution 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 & thorn; 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 signifi-cantly 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. (c) 2021 Elsevier Inc. All rights reserved

l-Carnitine supplementation for the prevention of postoperative atrial fibrillation in aortic valve surgery

Objectives l-Carnitine, a quaternary amine, improves fatty acid metabolism in the heart and has anti-inflammatory effects. Several studies have reported the efficacy of l-carnitine for the prophylaxis of arrhythmia. We assessed the clinical effectiveness of l-carnitine in preventing postoperative atrial fibrillation (POAF) in aortic valve surgery. Methods Thirty patients who underwent aortic valve surgery were included. Fifteen patients had no prophylaxis other than conventional measures (control), while 15 patients received oral l-carnitine for 9 days (daily dose of 3 g). The incidence of POAF during 1 week after surgery was compared between the two groups. The multivariable logistic regression analysis for POAF was performed using the pre- and intraoperative parameters. Results Preoperative characteristics and operative data were comparable between the groups. The POAF rate was significantly lower in the l-carnitine group than in the control (20% and 60%, respectively; P = 0.025). l-Carnitine use was an independently negative predictor for POAF (odds ratio 0.067; 95% confidence interval 0.006-0.768). Conclusions l-Carnitine administration may have potential for the prevention of POAF in aortic valve surgery

Cardioprotective effects of chloroquine pretreatment on ischemic and reperfusion injury via activation of ERK1/2 in isolated rat hearts

Purpose Several therapeutic agents have been found to prevent myocardial ischemic and reperfusion (I/R) injury after cardiac surgery; however, no drug is routinely used to afford cardioprotective benefits in clinical settings. Herein, we aimed to determine whether chloroquine (CQ) pretreatment attenuates I/R injury after global ischemia in isolated rat hearts and elucidate mechanisms underlying the effects of CQ. Methods Isolated rat hearts were subjected to 30-min global ischemia, followed by 60-min reperfusion with Krebs-Henseleit buffer (KHB). Immediately before ischemia, 10 mL of pretreatment solutions (KHB, n = 4 or KHB + CQ [100 mu M], n = 4) were injected through the aortic root. Cardiac function was examined based on the rate pressure product (RPP). Myocardial apoptosis was evaluated using TUNEL staining. To assess the reperfusion ischemia salvage kinase pathway, protein expression levels of AKT and extracellular signal-regulated kinase (ERK1/2) were determined using western blotting. To investigate the role of ERK1/2, an ERK1/2 selective inhibitor was used in eight additional rats. Results The recovery rate of the RPP was higher in the KHB + CQ group than in the KHB group 60 min after I/R (KHB, 44 +/- 3% vs. KHB + CQ, 69 +/- 7%; P = 0.019, d = 2.2). CQ pretreatment reduced apoptosis and enhanced the phosphorylation of ERK1/2; however, AKT phosphorylation was unaltered. In addition, the ERK1/2 inhibitor abolished CQ-mediated cardioprotective effects. Conclusions CQ pretreatment showed protective effects on cardiac function after I/R by activating ERK1/2

Protective effects of trehalose preconditioning on cardiac and coronary endothelial function through eNOS signaling pathway in a rat model of ischemia-reperfusion injury

Coronary endothelial dysfunction is a major cause of ischemia-reperfusion (I/R) injury. Trehalose, a natural disaccharide, has been reported to ameliorate endothelial dysfunction during aging by activating endothelial nitric oxide synthase (eNOS); however, its role in I/R injury is unknown. This study evaluated the effects of trehalose preconditioning on cardiac and coronary endothelial function after I/R. Langendorff-perfused rat hearts underwent 30 min of global ischemia followed by 80 min of reperfusion with or without trehalose preconditioning. Rate pressure product (RPP) and coronary flow (CF) were measured during reperfusion. Perivascular edema was assessed by hematoxylin and eosin staining. Myocardial oxidative stress and apoptosis were evaluated by immunohistochemistry and TUNEL staining, respectively. eNOS dimerization was determined by western blotting. An eNOS inhibitor was used to examine the role of eNOS. Trehalose preconditioning showed a higher recovery rate after I/R as indicated by high RPP (control vs. trehalose, 28 +/- 6% vs. 46 +/- 9%; P = 0.017, Cohen's d = 2.3) and CF values (35 +/- 10% vs. 55 +/- 9%; P = 0.025, d = 1.7). Furthermore, trehalose preconditioning reduced perivascular edema, myocardial oxidative stress, and apoptosis. The eNOS dimerization ratio was increased by trehalose (1.2 +/- 0.2 vs. 1.6 +/- 0.2; P = 0.023, d = 2.1), which was associated with the recovery of RPP and CF. These effects of trehalose were abolished by the eNOS inhibitor. Trehalose preconditioning showed protective effects on cardiac and coronary endothelial function after I/R through the eNOS signaling pathway

Feasibility and limitations of mitral valve repair, with or without left ventricular reconstruction in non-ischemic dilated cardiomyopathy

Background: Although non-transplant surgical interventions for non-ischemic dilated cardiomyopathy (NIDCM) are relatively effective, their feasibility and limitations have not been fully elucidated. The aim of this study was to define the feasibility and limitations of mitral valve repair, with or without surgical ventricular reconstruction for patients with NIDCM in terms of postoperative low cardiac output syndrome (LOS). Methods: Twenty non-transplant candidates (aged 57 ± 13 years) with NIDCM and significant mitral regurgitation had undergone mitral valve repair combined with submitral procedures. Using a 72-mL plastic ellipsoidal sizer, left ventricular reconstruction was performed concomitantly in 14/20 (70%) patients with extremely large ventricles. Total stroke volume, deceleration time of early trans-mitral flow wave, and the slope (Mw) in the preload recruitable stroke-work relationship were assessed using transthoracic echocardiography. LOS was defined as in-hospital death due to heart failure or a cardiac index less than 2.2 L/min/m2 before discharge. Results: There were three in-hospital deaths and four patients with postoperative cardiac index less than 2.2 L/min/m2 [n = 7 (35%), LOS group]. Preoperative total stroke volume, deceleration time, and the Mw were significantly lower in the LOS group compared to those in the non-LOS group; the predicted cut-off values for LOS were 84 mL/beat (p = 0.008), 133 ms (p = 0.015), and 45 erg cm-3 × 10^3 (p = 0.036), respectively. Preoperative left ventricular ejection fraction and ventricular size could not predict postoperative LOS. The one-year survival rate was 0% in the LOS group and 84% in the non-LOS group (p < 0.001). Conclusions: Mitral valve repair, with or without left ventricular reconstruction, could be contraindicated for NIDCM patients with low total stroke volume, deceleration time, and Mw in terms of high postoperative incidence of LOS. For high-risk patients, other therapeutic strategies might be necessary

The extent of papillary muscle approximation affects mortality and durability of mitral valve repair for ischemic mitral regurgitation

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