Severe Left Ventricular Failure Unmanageable by Impella 5.0.

Mechanical circulatory support can be beneficial for patients with cardiogenic shock. Of these, the Impella has recently become the first-line device due to its feasibility, minimal invasiveness, and efficacy. We had a 58-year-old male with acute myocardial infarction followed by cardiogenic shock. We initially placed the patient on intra-aortic balloon pumping, which was switched to Impella 2.5 and could stabilize him. Unfortunately, the Impella 2.5 device suddenly stopped on the fifth day, thus, we tried to manage him by inotropes. However, his condition gradually deteriorated, so we applied Impella 5.0. Although his systemic circulation could be maintained, severe pulmonary hypertension persisted on Impella 5.0. He developed flash pulmonary edema, thus, we emergently added venoarterial extracorporeal membrane oxygenation on Impella 5.0 (ECPELLA). Then, we removed Impella 5.0 and changed peripheral venoarterial extracorporeal membrane oxygenation to central venoarterial extracorporeal membrane oxygenation. In this central venoarterial extracorporeal membrane oxygenation, we inserted the cannulas in the pulmonary artery and the left ventricle in addition to the usual cannulas in the ascending aorta and the right atrium. We aimed to control pulmonary arterial blood flow for lung protection as well as left ventricular unloading by this modification. However, his cardiac function showed no signs of recovery, and his lung condition showed further exacerbation. He was complicated by fungal sepsis and finally died of multi-organ failure. Although the Impella is an option, it is crucial to evaluate patients' condition carefully and to escalate the device, if needed, without delay.

Acute Myocardial Infarction Due to Left Main Trunk Ostial Stenosis Occurring in the Acute Phase After Aortic Valve Replacement.

Coronary ostial stenosis is a rare but critical complication after aortic valve replacement. We present a patient with acute myocardial infarction that occurred eight days after aortic valve replacement. The patient had favorable progress until eight days after the operation, but she suddenly developed ventricular fibrillation and then pulseless electrical activity; thus, she was placed on venoarterial extracorporeal membrane oxygenation. Emergent coronary angiography revealed severe stenosis without thrombus nor dissection in the left main trunk orifice, and we realized that the prosthetic valve stent was quite close to the left main trunk orifice. She underwent stent implantation, and TIMI III flow was achieved. She could be weaned from venoarterial extracorporeal membrane oxygenation in 12 days and was stabilized without inotropes. Unfortunately, she was complicated by fungal sepsis and died from multi-organ failure 37 days after index surgery. The majority of coronary ostial stenosis is reported to occur within a few months after surgery because of its pathophysiological mechanisms. The onset of coronary ostial stenosis in the acute phase after surgery like in our case is not common. The deformity of the aortic complex after aortic valve replacement may trigger a left main trunk ostial stenosis. The change of aortic complex geometry after aortic valve replacement should be noted, especially in small patients or narrow aortic annulus.

[The use of high-dose oxycodone with midazolam for dyspnea due to end-stage heart failure in an older patient with renal insufficiency].

INTRODUCTION: We herein report a case of dyspnea in an older patient with end-stage heart failure and renal insufficiency successfully controlled with high-dose oxycodone plus midazolam. CASE: A 91-year-old womam with end-stage heart failure due to severe aortic stenosis and complete atrio-ventricular block developed dyspnea. We used continuous oxycodone subcutaneous injection instead of morphine for dyspnea due to renal insufficiency. Oxycodone relieved her dyspnea in a dose-dependent manner without serious adverse events. We also carefully administered midazolam for the dyspnea as well. CONCLUSION: We used high-dose oxycodone plus midazolam to manage dyspnea in an older patient with end-stage heart failure and renal insufficiency. High-dose oxycodone with midazolam might be useful for treating dyspnea under careful observation.

Dexmedetomidine for dyspnoea.

Dexmedetomidine is a selective α2-adrenoreceptor agonist with a broad range of effects, including easily controllable sedation, analgesia and anxiolysis. Because of these favorable features, it has replaced traditional sedatives, such as benzodiazepines, and is becoming the first-line sedative for the patients in intensive care units. Terminally ill patients often need sedatives for symptom management, especially for dyspnoea. However, the use of dexmedetomidine in a palliative care setting has rarely been recognised to date. We experienced a patient nearing the end of life due to uncontrollable pulmonary haemorrhage on ventilator, whose dyspnoea was successfully managed by dexmedetomidine in addition to continuous intravenous infusion of oxycodone.

Perforation of the right atrial appendage during implantation of a leadless pacemaker.

We report a case of perforation of the right atrial appendage during implantation of a leadless pacemaker in a 94 years old woman. We performed emergency surgery to repair the perforation site. To our konwledge, there are few reports of right atrial perforation during a leadless pacemaker indwelling.

Usefulness of hybrid veno-arterial extracorporeal membrane oxygenation for lung ischemia-reperfusion injury after biventricular assist device implantation.

We experienced a case of fulminant myocarditis complicated by severe lung ischemia-reperfusion injury after switching from veno-arterial extracorporeal membrane oxygenation to biventricular assist device. We controlled lung blood flow by hybrid veno-arterial extracorporeal membrane oxygenation, which was established by modifying the biventricular assist device circuit without resternotomy, blood delivery to the pulmonary artery and blood removal from the left ventricle in addition to central veno-arterial extracorporeal membrane oxygenation, and accelerated lung recovery. The patient's lung damage and cardiac function were restored, and she completely recovered and was discharged without any complications. Regulation of lung blood flow is important and effective for lung ischemia-reperfusion injury after biventricular assist device implantation.

Electrodiagnostic assessment of the autonomic nervous system: A consensus statement endorsed by the American Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology.

Evaluation of disorders of the autonomic nervous system is both an art and a science, calling upon the physician's most astute clinical skills as well as knowledge of autonomic neurology and physiology. Over the last three decades, the development of noninvasive clinical tests that assess the function of autonomic nerves, the validation and standardization of these tests, and the growth of a large body of literature characterizing test results in patients with autonomic disorders have equipped clinical practice further with a valuable set of objective tools to assist diagnosis and prognosis. This review, based on current evidence, outlines an international expert consensus set of recommendations to guide clinical electrodiagnostic autonomic testing. Grading and localization of autonomic deficits incorporates scores from sympathetic cardiovascular adrenergic, parasympathetic cardiovagal, and sudomotor testing, as no single test alone is sufficient to diagnose the degree or distribution of autonomic failure. The composite autonomic severity score (CASS) is a useful score of autonomic failure that is normalized for age and gender. Valid indications for autonomic testing include generalized autonomic failure, regional or selective system syndromes of autonomic impairment, peripheral autonomic neuropathy and ganglionopathy, small fiber neuropathy, orthostatic hypotension, orthostatic intolerance, syncope, neurodegenerative disorders, autonomic hyperactivity, and anhidrosis.

A case of HeartMate II implantation in non-dilated left ventricle.

Left ventricular assist device is an established therapeutic option for the patient with end-stage heart failure. Recently, durable continuous-flow devices have replaced earlier generation of pulsatile devices and their desirable features are accelerating the utilization of these devices. However, their powerful performance could sometimes induce unfavorable complications such as sucking, especially in not so dilated left ventricle. Special maneuvers such as cannula position and lower pump speed may be reasonable for patients with non-dilated left ventricular, however, those managements have not been established yet to date. Right ventricular failure is also another concern in these devices. We experienced a patient who got a HeartMate II in spade-shaped, non-dilated left ventricle concomitant with right ventricular dysfunction, and successfully managed her.

Impact of Change in Body Mass Index on Outcomes After Left Ventricular Assist Device Implantation in Obese Patients.

Obesity could be a risk factor portending a poor prognosis after left ventricular assist device (LVAD) implantation. We sought to determine the impact of change in body mass index (BMI) on outcomes in obese patients supported by LVAD. Fifty-nine patients, who received LVAD between January 2010 and June 2015, with BMI ≥30 kg/m at the time of LVAD implantation, were retrospectively analyzed. Patients were divided into two groups based upon whether BMI after 6 months of device support decreased when compared with before. Thirty-eight patients who experienced decrease in BMI (group D) were compared with 21 patients whose BMI increased (group I). Baseline characteristics were similar between the groups except for body weight and BMI, which were significantly higher in group D (BMI: 35.9 ± 4.0 kg/m vs. 33.4 ± 3.5 kg/m; p = 0.018). During mean follow-up of 560 ± 178 days, group I had significantly higher incidence of infection [events per patient-years (eppy): nondevice related: 0.18 vs. 0.35, p = 0.01; device related: 0.1 vs. 0.32, p < 0.01; sepsis: 0.1 vs. 0.32, p < 0.01], heart failure (eppy: 0.1 vs. 0.25, p < 0.01), and renal failure (eppy: 0.03 vs. 0.14, p < 0.01). Survival at 2 years was significantly lower in group I (84.8% vs. 57.1%, p = 0.025). Increase in BMI in obese patients on LVAD is associated with worse survival with a higher incidence of infection, heart failure, and renal failure. Weight control may be a modifiable factor to improve prognosis.

Assimilation of satellite data to 3D hydrodynamic model of Lake Säkylän Pyhäjärvi.

To analyze the applicability of direct insertion of total suspended matter (TSM) concentration field based on turbidity derived from satellite data to numerical simulation, dispersion studies of suspended matter in Lake Säkylän Pyhäjärvi (lake area 154 km²; mean depth 5.4 m) were conducted using the 3D COHERENS simulation model. To evaluate the practicality of direct insertion, five cases with different initialization frequencies were conducted: (1) every time, when satellite data were available; (2) every 10 days; (3) 20 days; (4) 30 days; and (5) control run without repeated initialization. To determine the effectiveness of initialization frequency, three methods of comparison were used: simple spatial differences of TSM concentration without biomass in the lake surface layer; averaged spatial differences between initialization data and the forecasts; and time series of TSM concentration and observation data at 1 m depth at the deepest point of the lake. Results showed that direct insertion improves the forecast significantly, even if it is applied less often.

Utility of left ventricular systolic torsion derived from 2-dimensional speckle-tracking echocardiography in monitoring acute cellular rejection in heart transplant recipients.

BACKGROUND: Reduced left ventricular torsion (LV-tor) has been reported to be associated with acute rejection in heart transplant (HTx) recipients. We investigated the utility of LV-tor analysis derived from 2-dimensional speckle-tracking echocardiography (2D-STE) for detecting allograft rejection. METHODS: A total of 301 endomyocardial biopsies (EMBs), right heart catheterizations and echocardiograms were performed in 32 HTx recipients. Echocardiography was done within 3 hours from EMB or simultaneously with the procedures. The LV-tor was defined as the difference between apical and basal end-systolic rotations. The LV-tor values with and without cellular rejection were compared. In addition, we investigated whether the change in LV-tor values predicts the change in rejection grade in each patient. The baseline LV-tor value in each patient was defined as a mean value of the first 3 LV-tor measurements obtained when the patient was free from rejection. RESULTS: According to the conventional International Society for Heart and Lung Transplantation criteria, 274 biopsies showed a rejection Grade of 0, 1a or 1b (Group AR(-)), whereas 27 biopsies were Grade 2 or higher (Group AR(+)). LV-tor decreased more in Group AR(+) than in Group AR(-) (9.3 ± 0.7 vs 12.2 ± 0.2 degrees, p < 0.0001). In the LV-tor measurement for each patient, the 25% reduction in LV-tor value from baseline predicted Grade 2 or higher rejection with a predictive accuracy of 92.9%. CONCLUSION: LV-tor derived from 2D-STE could be of clinical value for non-invasive monitoring of acute rejection in HTx recipients.

Clinical course and outcome of heart transplant recipients: single center experience at the National Cardiovascular Center in Japan.

The number of heart transplant (HTx) surgeries in Japan is expected to increase under the Revised Organ Transplant Law. To date, among 69 HTx surgeries performed in Japan, 27 operations (39.1%) were performed at our institution, the National Cardiovascular Center (NCVC), located in Osaka. We have reviewed the outcomes of HTx conducted at NCVC during a 10 year period (May 1999 to January 2009). Among 27 heart transplant recipients at NCVC, the clinical charts of 26 recipients whose post-HTx period exceeded 1 year were retrospectively reviewed and compared to data from the International Society for Heart and Lung Transplantation (ISHLT) Registry. The survival rate of our recipients was 96.2% at 10.8 years, which was excellent even compared to the ISHLT Registry. The immunosuppressive regimen at NCVC was equivalent to that of the ISHLT Registry, except for more frequent use of Muromonab-CD3 (26.9% versus 3.3%, P < 0.0001) and an initial CSA-based regimen (65.3% versus 34.4%, P < 0.001). The drug we use for induction therapy has been recently changed from Muromonab-CD3 to Basiliximab. The incidences of post-HTx hypertension, diabetes, hyperlipidemia, and renal insufficiency were significantly less in patients at NCVC compared to those in the ISHLT Registry, however, the incidence of transplant coronary artery disease (TxCAD) was almost identical. Clinical review of post-HTx outcome at NCVC can provide useful information for Japanese transplant cardiologists who will engage in HTx management.

Improved long-term performance of pulsatile extracorporeal left ventricular assist device.

BACKGROUND AND PURPOSE: The majority of heart transplant (HTx) candidates require left ventricular assist device (LVAD) support for more than 2 years before transplantation in Japan. However, the only currently available device is the extracorporeal pulsatile LVAD. The long-term management of extracorporeal LVAD support has improved remarkably over the years. To determine which post-operative management factors are related to the long-term survival of patients on such LVAD, we retrospectively compared the incidence of complications and their management strategies between the initial and recent eras of LVAD use, classified by the year of LVAD surgery. METHODS: Sixty-nine consecutive patients supported by extracorporeal pulsatile LVAD as a bridge to HTx between 1994 and 2007 were reviewed retrospectively. The patients were assigned according to the time of LVAD surgery to either group A (n=30; between 1994 and 2000) or group B (n=39; between 2001 and 2007). RESULTS: Patients in group B survived significantly longer on LVAD support than those in group A (674.6 vs. 369.3 days; p<0.001). The 1- and 2-year survival rates were significantly higher in group B than that in group A (82% vs. 48%, p<0.0001; 68% vs. 23%, p<0.0001, respectively). The proportion of deaths due to cerebrovascular accidents was lower (17% vs. 50%, p<0.001) in group B compared with group A. The incidences of systemic infection were similar in both groups, but the proportions of patients alive and achieving transplant surgery after systemic infection were higher in group B than those in group A (55% vs. 14%, p<0.01; 14% vs. 36%, p<0.05, respectively). CONCLUSIONS: The long-term survival of patients even on "first-generation" extracorporeal LVAD has improved significantly in the recent era. Careful management of cerebrovascular accidents and systemic infection will play important roles in the long-term LVAD management.

Chest computed tomography of a patient revealing severe hypoxia due to amniotic fluid embolism: a case report.

INTRODUCTION: Amniotic fluid embolism is one of the most severe complications in the peripartum period. Because its onset is abrupt and fulminant, it is unlikely that there will be time to examine the condition using thoracic computed tomography (CT). We report a case of life-threatening amniotic fluid embolism, where chest CT in the acute phase was obtained. CASE PRESENTATION: A 22-year-old Asian Japanese primiparous woman was suspected of having an amniotic fluid embolism. After a Cesarean section for cephalopelvic disproportion, her respiratory condition deteriorated. Her chest CT images were examined. CT findings revealed diffuse homogeneous ground-glass shadow in her bilateral peripheral lung fields. She was therefore transferred to our hospital. On admission to our hospital's intensive care unit, she was found to have severe hypoxemia, with SpO2 of 50% with a reservoir mask of 15 L/min oxygen. She was intubated with the support of noninvasive positive pressure ventilation. She was successfully extubated on the sixth day, and discharged from the hospital on the twentieth day. CONCLUSION: This is the first case report describing amniotic fluid embolism in which CT revealed an acute respiratory distress syndrome-like shadow.

Body mass index is a useful predictor of prognosis after left ventricular assist system implantation.

BACKGROUND: The obesity paradox has recently attracted considerable interest in the study of many diseases. In this investigation we examine the relationship between body mass index (BMI) and prognosis after left ventricular assist system (LVAS) implantation. METHODS: We measured the BMI of 64 patients 3 months after LVAS implantation for end-stage heart failure. The patients were classified according to BMI into Group A (BMI <16 kg/m(2)), Group B (BMI 16 to 18.4 kg/m(2)) or Group C (BMI > or =18.5 kg/m(2)). We compared the prognosis among these three groups after a mean follow-up period of 583 days. RESULTS: Seven patients were weaned from their LVAS, 24 received heart transplantation, 25 died on the transplant waiting list, and 8 remain on the list. Long-term (>1 year) mortality was significantly higher in Group A than in Groups B and C (59% vs 40% and 18%, respectively; p < 0.05). The incidence of sepsis was also significantly higher in Group A than in Groups B and C (68% vs 45% and 32%, respectively; p < 0.05). After multivariate adjustment, BMI <16 kg/m(2) (hazard ratio [HR] 14.9; 95% confidence interval [CI] 2.61 to 86.0; p < 0.01) and levels of C-reactive protein (HR 1.56; 95% CI 1.15 to 2.13; p < 0.01) were independent predictors of mortality. CONCLUSIONS: A lower BMI indicated a poor prognosis, as well as a higher incidence of a fatal complication, sepsis, after LVAS implantation. Control of BMI could be an effective way to improve management of patients with LVAS.

Drug interaction between tacrolimus and carbamazepine in a Japanese heart transplant recipient: a case report.

This article reports changes in tacrolimus (FK506) blood levels connected with carbamazepine (CBZ). A drug interaction between FK506 and CBZ was investigated in a woman, who was in her 40s, who underwent heart transplantation. Pharmacokinetic parameters were measured, including dose and trough blood levels (C(0)), area under the serum concentration-time curve from 0 to 12 hours (AUC(0-12h)), and apparent clearance of oral FK506 (CL/F) for FK506 alone (about 3 months before starting CBZ) and combined with CBZ (11 days and about 3 months after starting CBZ). FK506 C(0) levels were decreased within 7 days of CBZ treatment. FK506 dosing required a 1.3- to 1.4-fold increase to maintain adequate blood levels while taking 200 mg CBZ daily. The AUC(0-12h)/dose 11 days after CBZ treatment was about 50% of the value before CBZ, and was about 70% at 3 months after CBZ treatment. The CL/F at 11 days and about 3 months after starting CBZ treatment was about 2 times higher than before CBZ therapy. FK506 C(0) levels are decreased by CBZ treatment, and blood levels should be closely monitored.

Experience of appendicular thermal therapy applied to a patient with a left ventricular assist device awaiting heart transplantation.

Thermal therapy for heart failure is recognized to improve clinical symptoms. We describe our experience with appendicular thermal therapy applied to a patient fitted with an extracorporeal left ventricular assist device (LVAD) who was wait-listed for a heart transplant. A 21-year-old male with end-stage heart failure due to dilated cardiomyopathy was fitted with a LVAD. His general condition stabilized after LVAD placement and the status of his heart failure has remained at NYHA class II for the past 13 months. However, his cardiac function did not sufficiently recover to discontinue LVAD support. We conducted appendicular thermal therapy using a steam foot bath and heated gloves for 2 weeks. Immediately after thermal therapy, his average sublingual temperature increased from 36.3 to 37.0 degrees C and the grade of mitral regurgitation, as well as LV ejection fraction and endothelial function improved. Furthermore, levels of oxidative and anti-oxidative stress markers decreased and increased, respectively, after 2 weeks of therapy. No complications developed. We conclude that appendicular thermal therapy was safe in this patient waiting for a heart transplant and who had an extracorporeal LVAD, and that the procedure might be beneficial for others with end-stage heart failure.

An adult patient with Kabuki syndrome presenting with Henoch-Schönlein purpura complicated with pulmonary hemorrhage.

We present a case of a 33-year-old woman with Kabuki syndrome (KS) presenting with Henoch-Schönlein purpura (HSP). She was admitted to our hospital with a brain abscess in the lateral ventricle and meningitis. She had been diagnosed with KS. Skin eruptions had appeared on her lower extremities, with arthralgia, cough, and hemoptysis. She suddenly developed pulmonary hemorrhage and respiratory failure. We intubated her trachea and started mechanical ventilation in the intensive care unit (ICU). Skin biopsy revealed leukocytoclastic vasculitis with granular depositions of immunoglobulin A (IgA) in dermal vessel walls, and she was diagnosed as having HSP. Supportive management and prednisolone at 20 mg x day(-1) cured the pulmonary hemorrhage and respiratory failure. On ICU day 27, she was weaned from mechanical ventilation. Pulmonary hemorrhage as a complication of HSP is rare and sometimes fatal. KS is often associated with an increased incidence of infection and congenital heart disease. Susceptibility to infection and pulmonary hypertension due to congenital heart disease in this patient may have led to the development of the pulmonary hemorrhage. Supportive care and steroid therapy appeared to be beneficial in the treatment of this patient with HSP with pulmonary hemorrhage.

Limited sampling strategy for mycophenolic acid in Japanese heart transplant recipients: comparison of cyclosporin and tacrolimus treatment.

BACKGROUND: The purpose of the study was to characterize the pharmacokinetics of mycophenolic acid (MPA) in Japanese heart transplant recipients and to find the time point that has the best correlation with the MPA area under the plasma concentration curve (AUC). METHODS AND RESULTS: Twenty-two Japanese recipients treated with mycophenolate mofetil were evaluated in the study. Approximately 9 months after transplantation, the area under the MPA serum concentration-time curve from 0 to 12 h (AUC(0-12 h)) was evaluated. The MPA AUC(0-12 h) h values in the cyclosporine (CsA) and tacrolimus (FK) groups ranged from 13.11 to 50.98 mug . h/ml and from 39.19 to 93.18 mug . h/ml, respectively. Fourteen models were developed and analyzed for their ability to estimate the MPA AUC(0-12 h) based on a limited number of samples in the CsA group. Sixteen models were developed in the FK group. The best model for predicting the full MPA AUC(0-12 h) in the CsA group was a 3-time-point model that included C(0 h), C(1 h) and C(2 h) (r(2), 0.96; mean prediction error, 0.15+/-7.85%); a 2-time-point model that included C(0 h), and C(2 h) (r(2), 0.94; mean prediction error, 0.495+/-10.35%) was also reliable. In the FK group, a 3-time-point model that included C(1 h), C(2 h) and C(4h) (r(2), 0.73; mean prediction error, 2.73+/-17.09%) was the best model for predicting the full MPA AUC(0-12 h), but it was not reliable in clinical practice. CONCLUSION: A 3-(C(0 h), C(1 h) and C(2 h)) and a 2-time-point model (C(0 h) and C(2 h)) are useful for predicting the full MPA AUC(0-12 h) in Japanese heart transplant recipients treated with CsA but not with FK.

Spironolactone modulates expressions of cardiac mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase 2 and prevents ventricular remodeling in post-infarct rat hearts.

Aldosterone antagonists have been reported to prevent ventricular remodeling after myocardial infarction (MI) via their action to extracellular matrix (ECM). However, it remains largely unknown whether aldosterone antagonists attenuate myocyte loss in the remodeling process. The present study examined whether spironolactone prevents myocyte apoptosis and improves post-infarct ventricular remodeling in rats. MI was achieved by permanent occlusion of the left coronary artery. Administration of spironolactone (100 mg/kg/day) was started immediately after MI. Sprague-Dawley rats were divided into four groups: 1) sham, 2) spironolactone-treated sham, 3) untreated MI, 4) spironolactone-treated MI. Echocardiographic parameters (left ventricular [LV] diastolic dimension [LVDd], fractional shortening [%FS]), hemodynamic parameters (LV systolic pressure [LVSP], LV end-diastolic pressure [LVEDP], dP/dt(max) and dP/dt(min)) and collagen accumulation quantitated by Masson's Trichrome staining were significantly improved in the spironolactone-treated MI group on the 14th day, compared with the untreated MI group. Moreover, the percentage of apoptotic myocytes evaluated by terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay was significantly lower in the spironolactone-treated MI group on the 2nd (3.54% vs. 5.79% in untreated MI group), 7th (0.65% vs. 1.37% in untreated MI group) and 14th days (0.11% vs. 0.16% in untreated MI group). Real time reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the expression of mineralocorticoid receptor (MR) mRNA and that of 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) mRNA, which is known to confer aldosterone selectivity on MR, were upregulated in the untreated MI group, and that spironolactone significantly suppressed the expression of these genes. Moreover, spironolactone significantly inhibited aldosterone-induced apoptosis in cultured rat cardiac myocytes in a dose-dependent fashion. Our study demonstrates that, in addition to their effect on ECM, aldosterone antagonists inhibit myocyte apoptosis and prevent post-infarct ventricular remodeling by modulating the expression levels of MR and 11beta-HSD2, which are enhanced in the remodeling heart.