Taro Sasaoka

Post-resuscitation myocardial microcirculatory dysfunction is ameliorated with eptifibatide.

BACKGROUND The post-cardiac arrest syndrome includes a decline in myocardial microcirculation function. Inhibition of the platelet IIb/IIIa glycoprotein receptor has improved myocardial microvascular function post-percutaneous coronary intervention. Therefore, we evaluated such inhibition with eptifibatide for its effect on myocardial microcirculation function post-cardiac arrest and resuscitation. METHODS Four groups of swine were studied in a prospective, randomized, blinded, placebo-controlled protocol including; eptifibatide administered during CPR (Group 1, n=5), after resuscitation (Group 2, n=4), during and after resuscitation (Group 3, n=5), or placebo (Group 4, n=10). CPR was initiated following 12min of untreated VF. Those successfully resuscitated were studied during a 4-h post-resuscitation period. Coronary flow reserve, a measure of microcirculation function (in the absence of coronary obstruction), as well as parameters of left ventricular systolic and diastolic function, were measured pre-arrest and serially post-resuscitation. RESULTS Coronary flow reserve was preserved during the post-resuscitation period, indicating normal microcirculatory function in the eptifibatide-treated animals, but not in the placebo-treated group. However, LV function declined equally in both groups during the first 4h after cardiac arrest. CONCLUSION Inhibition of platelet IIb/IIIa glycoprotein receptors with eptifibatide post-resuscitation prevented myocardial microcirculation dysfunction. Left ventricular dysfunction post-resuscitation was not improved with eptifibatide, and perhaps transiently worse at 30min post-resuscitation. Post-cardiac arrest ventricular dysfunction may require a multi-modality treatment strategy for successful prevention or amelioration.

Comparison of outcomes after everolimus-eluting stent implantation in diabetic versus non-diabetic patients in the Tokyo-MD PCI study

BACKGROUND Diabetes mellitus (DM), especially in those requiring insulin for treatment, is known to be a risk factor for adverse events after percutaneous coronary intervention using first-generation drug-eluting stents. However, the role of DM in patients treated with everolimus-eluting stents (EES) is less known. The purpose of the present analysis was to evaluate the outcomes of treatment with EES for DM patients both requiring and not requiring insulin, and to compare them with non-DM patients. METHODS Of patients treated with EES in the Tokyo-MD PCI study, an all-comer, multicenter, observational cohort study, we identified 199 insulin-requiring diabetics (IRDM), 575 non-insulin requiring diabetics (NIRDM), and 1092 non-diabetics (non-DM). The main outcomes were major adverse cardiovascular events (MACE) defined as a composite of all-cause death, myocardial infarction, and stroke, and target lesion revascularization (TLR). RESULTS The cumulative incidence of MACE and TLR was significantly greater in patients with IRDM than non-DM [MACE: hazard ratio 1.97, 95% confidence interval (CI) 1.31-2.90, p<0.01; TLR: hazard ratio 3.43, 2.07-5.55, p<0.0001] according to univariate Cox proportional hazards model. After adjusting for confounders using the multivariate Cox proportional hazard model, the risk of IRDM versus non-DM for TLR remained significant (hazard ratio 1.92, 1.10-3.29, p=0.02). The incidence of TLR in NIRDM was slightly greater than that in non-DM according to univariate analysis (hazard ratio 1.65, 1.07-2.54, p=0.02). However, the risk was not statistically different in the multivariate analysis (hazard ratio 1.52, 0.97-2.35, p=0.06). CONCLUSIONS In this all-comer, observational study, the risk of TLR was greater in IRDM compared with non-DM after EES implantation, while the increased risk for TLR from NIRDM did not reach statistical significance.

Common Occurrence of Everolimus-Associated Aphthous Stomatitis in Japanese Heart Transplant Recipients

Mammalian target of rapamycin (mTOR) inhibitors display antiproliferative effects with less nephrotoxicity than calcineurin inhibitors. However, clinical use of mTOR inhibitors can be associated with a series of adverse events. We experienced cases of aphthous stomatitis associated with everolimus (EVL) in four Japanese heart transplant recipients treated at the target trough EVL blood level after a switch from mycophenolate mofetil between April and December 2007. All four patients developed aphthous stomatitis; three required reduction of the exposure and one, EVL discontinuation due to stomatitis as well as other side effects. All patients recovered from stomatitis after reduction or withdrawal of EVL. Thus, we considered that EVL-related stomatitis might occur commonly among the Japanese population. The proper dosage, effects, and frequency of the side effects of mTOR inhibitors may vary by ethnic population.

Incidence and predictors of early and late target lesion revascularization after everolimus‐eluting stent implantation in unselected patients in japan

The objective of this study was to clarify the incidence and predictors of early and late target lesion revascularization (TLR) after everolimus‐eluting stent (EES) implantation in actual clinical practice.

The Hypercholesterolemia Paradox in Percutaneous Coronary Intervention: An Analysis of a Multicenter PCI Registry

Objective The aim of this study was to assess the relationship between hypercholesterolemia (HC) and clinical events through a percutaneous coronary intervention (PCI) registry. HC is a well-known independent risk factor for long-term cardiovascular events after PCI. However, it has been reported to be associated with a lower risk of adverse events in patients with cancer or acute coronary syndrome. Methods We analyzed the relationship between HC and adverse events in patients treated with everolimus-eluting stents (EESs) through the Tokyo-MD PCI study (an all-comer, multicenter, observational registry). The propensity score method was applied to select two groups with similar baseline characteristics. Results The unadjusted population included 1,536 HC patients and 330 non-HC patients. Propensity score matching yielded 314 matched pairs. After baseline adjustment, the outcomes of HC patients were significantly better than those of the non-HC patients with respect to the primary endpoint, which was a combination of mortality from all causes, nonfatal myocardial infarction (MI), nonfatal neurological events, and major bleeding [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.39-0.81; p=0.002], and the secondary endpoints, which included a combination of mortality from all causes, nonfatal MI, and nonfatal neurological events (HR 0.59, 95% CI 0.39-0.88; p=0.01), and major bleeding (HR 0.42, 95% CI 0.20-0.88; p=0.02). A subgroup analysis showed age as an interaction factor for the primary endpoint (interaction p=0.035). Conclusion HC was associated with better outcomes in patients who underwent EES implantation, even after baseline adjustment.

Effectiveness of the proximal optimization technique for longitudinal stent elongation caused by post‐balloon dilatation

OBJECTIVES To evaluate the effectiveness of the proximal optimization technique (POT) to prevent longitudinal stent elongation. BACKGROUND The mechanism of stent elongation, which occurs after post-balloon dilation, is still unclear. METHODS A total of 103 lesions treated with optical coherence tomography guided coronary intervention between May 2013 and November 2017 were retrospectively analyzed. Lesions were divided according to the circumferential degree of malapposition at the stent edge immediately after deployment into well-apposed group (<180°) and malapposed group (≥180°). Post-dilation was performed from distal to proximal within the stent until August 2016 (non-POT cohort), and POT was applied thereafter (POT cohort). In the POT cohort, post-dilation was done at the proximal portion of the stent with sufficiently large balloon to minimize malapposition followed by distal dilatations. Stent elongation length was defined as the change in stent length from stent deployment to after post-dilatation. RESULTS In the non-POT cohort, 72 lesions, including 54 lesions in the well-apposed group and 18 in the malapposed group were analyzed. Stent elongation length was significantly longer in the malapposed group than in the well-apposed group (1.51 ± 1.34 mm vs 0.13 ± 0.84 mm, P < 0.01). In the POT cohort, 31 lesions including 21 in the well-apposed group and 10 in the malapposed group were analyzed. Stent elongation length was not significantly different between the groups (-0.09 ± 0.91 mm vs 0.30 ± 0.99 mm, P = 0.29). CONCLUSIONS Malapposition of the stent edge is responsible for longitudinal stent elongation caused by post-dilatation. POT appeared to effectively prevent longitudinal stent elongation.

Long-term clinical outcomes of permanent polymer everolimus-eluting stent implantation following rotational atherectomy for severely calcified de novo coronary lesions: Results of a 22-center study (Tokyo-MD PCI Study)

BACKGROUND Long-term clinical outcomes of permanent polymer everolimus-eluting stent (PP-EES) implantation after rotational atherectomy (RA) have not been fully evaluated. We sought to investigate the long-term clinical outcomes of PP-EES implantation after RA and assess the impact of hemodialysis on this treatment strategy. METHODS Patients who underwent percutaneous coronary intervention (PCI) with PP-EES at 22 institutions between January 2010 and December 2011 were enrolled in this multicenter, observational trial. From a total of 1918 registered patients, 113 patients with 115 de-novo lesions who underwent PCI with PP-EES following RA were retrospectively analyzed. The primary endpoint was a major adverse cardiac event (MACE) defined as the composite of cardiac death, non-fatal myocardial infarction (MI), and clinically driven target lesion revascularization (TLR). RESULTS Long-term follow-up was available for 112 patients (99.1%). The median follow-up period was 2.9 (interquartile range 1.9-3.6) years. The mean age of the patients was 72.3 ± 8.8 years and 64 patients (56.6%) had chronic kidney disease (≥stage 3, 42 on hemodialysis). The cumulative incidences of MACE, non-fatal MI, and TLR were 22.1%, 5.3%, and 10.6%, respectively. Coxs proportional hazards analysis showed that the independent predictors of TLR were hemodialysis and chronic total occlusion. (HR, 14.1; 95% CI, 1.74-155.5; p = 0.01, HR, 9.01; 95% CI, 1.34-62.5; p = 0.02). CONCLUSIONS PP-EES implantation after lesion modification by RA is considered to be a feasible treatment strategy for heavily calcified lesions. Hemodialysis and chronic total occlusion appeared to be associated with TLR.

Effect of aortic regurgitant jet direction on mitral valve leaflet remodeling: a real-time three-dimensional transesophageal echocardiography study

Chronic aortic regurgitation (AR) induces mitral valve (MV) leaflet enlargement, although, its mechanism still remains unclear. This study aimed to clarify the influence of AR jet directions on the MV apparatus in patients with chronic AR. This study included 69 consecutive patients with severe chronic AR and 17 controls who underwent three-dimensional (3D) transesophageal echocardiography (TEE). The anterior mitral leaflet (AML), posterior mitral leaflet (PML) and MV annulus areas were measured at mid-diastole. All AR patients were classified into the posterior (Group A, n = 38) or non-posterior (Group B, n = 31) group based on the AR jet directions. Both two groups revealed the increased total leaflet areas compared with the controls. No significant differences in the left ventricular volumes, PML or MV annulus area were observed between Group A and B; however, Group A had the larger AML area and greater AML/PML area ratio than Group B (both P < 0.01). The multivariate analysis indicated that the posterior AR jet was independently associated with the AML/PML area (P < 0.01). 3D TEE depicted geometric differences in the MV apparatus between the different types of AR jet directions. These results may be helpful in understanding the mechanism of MV leaflet remodeling in chronic AR.

Long-Term Management of Pulsatile Extracorporeal Left Ventricular Assist Device

Heart transplantation provides considerable survival benefits for patients with end-stage heart failure, but it is available for only a small fraction of such patients all over the world due to donor shortage. Therefore, many heart transplant candidates require long-term support by a left ventricular assist device (LVAD) while they await transplantation. However, the long-term LVAD support can result in serious complications such as cerebrovascular accident (CVA) and infection, which are the leading cause of death and the primary reason for elimination from transplant eligibility in patients supported by LVAD (Rose EA et al., 2001; Holman WL et al., 2009). In Japan, only less than 100 organ transplants from brain-dead donors have been performed over the past 10 years. The mean waiting period for heart transplant candidates after LVAD surgery frequently exceeds 2 years. In addition, the only available LVAD covered by the National Health Insurance System in Japan is pulsatile extracorporeal LVAD (ToyoboLVAS®; Nipro, Tokyo, Japan). Implantable LVADs have not yet been approved and are still under clinical trials, awaiting approval by the Ministry of Health, Labour and Welfare as of October 2010. Toyobo-LVAS® was primarily designed for short-term support, but it is used in Japan over the long term as a ‘bridge-to-transplant’ device (Figure 1). Patients supported by pulsatile extracorporeal LVAD cannot be discharged from the hospital, and cannot leave the intensive care ward without attendant medical doctors. Some patients required to be supported by such device for 4 years until being transplanted. Given these circumstances, the long-term management skills of Japanese cardiologists for overcoming “extracorporeal pulsatile” LVAD–related complications have improved over time, with the 1-year survival now being 82% (Sasaoka T et al., 2010). The extracorporeal pulsatile LVAD is the devise that is not utilized in a first line anymore in a world except for Japan. However, CVA and infection, on which we have paid considerable attention during long-term management of extracorporeal pulsatile LVAD, still remain to be important complication even in the era of new generation continuous flow devises. Therefore, we believe that our delicate care for such complication to accomplish long-term survival in patients supported by extracorporeal pulsatile LVAD is worthwhile information even today. In this chapter, we focused on the management strategies of CVA and infection in patients with extracorporeal pulsatile LVAD according to our past 10 years experience.