Macular Microvascular Perfusion Status in Hypertensive Patients with Chronic Kidney Disease.

To compare retinal microvascular perfusion between the eyes of hypertensive patients with and without chronic kidney disease (CKD), the vessel density (VD) and fractal dimension (FD) of the superficial (SVP) and deep retinal vascular plexus (DVP) were analyzed on 6 × 6 mm fovea-centered optical coherence tomography angiography (OCTA) images of patients with hypertension. The retina was divided into an inner ring (IR) and outer ring (OR) according to the Early Treatment of Diabetic Retinopathy Study grid. The glomerular filtration rate (GFR) was determined and CKD was diagnosed (GFR < 60 mL/min/1.73 m2). Ninety-six eyes from 52 patients with hypertension were included in this analysis. Twenty patients (n = 37 eyes) were diagnosed with CKD. The mean age was 69 ± 11.7 years and 60.4 ± 9.2 years in the CKD group and in the control group, respectively. The univariate model revealed a significant difference in VD between patients without and with CKD in the superficial IR (0.36 ± 0.03 vs. 0.34 ± 0.04, p = 0.03), the superficial OR (0.35 ± 0.02 vs. 0.33 ± 0.04, p = 0.02), the deep OR (0.24 ± 0.01 vs. 0.23 ± 0.02, p = 0.003), and the FD in the SVP (1.87 ± 0.01 vs. 1.86 ± 0.02, p = 0.02) and DVP (1.83 ± 0.01 vs. 1.82 ± 0.01, p = 0.006). After adjusting for age and sex, these differences did not remain statistically significant. Similar results were observed for the FD in the SVP and DVP. In our cohort, patients with hypertension and CKD did not differ from patients without CKD in regard to microvascular perfusion status in the macular area as assessed using OCTA.

Surgical Transmitral Thrombectomy to Prevent Recurrent Stroke in Acute Myocardial Infarction.

Left ventricular (LV)-thrombi occur in up to 14 % of patients with acute myocardial infarction (AMI) in the era of primary percutaneous coronary intervention. For these patients, anticoagulant therapy (AC) is recommended by AMI-guidelines. When, despite AC, LV-thrombi lead to embolism, surgical thrombectomy is an option, which is not mentioned or not recommended in AMI-guidelines. We report a 46-year old female patient with AMI. An 80 % stenosis of the proximal left anterior descending coronary artery was treated by a drug-eluting stent. Thrombi within the akinetic LV-apex became mobile despite AC and dual antiplatelet therapy, and a cerebellar stroke occurred. By a transmitral surgical approach with endoscopic assistance the thrombi were completely removed. Postoperative course and 12-months follow-up were uneventful. LV-thrombi should be observed carefully regarding changes in morphology. Surgical thrombectomy of LV-thrombi is a rare treatment option to prevent imminent embolism. Benefits versus risks of surgical removal of LV-thrombi need to be carefully weighted.

Empagliflozin in acute myocardial infarction: the EMMY trial.

AIMS: Sodium-glucose co-transporter 2 inhibition reduces the risk of hospitalization for heart failure and for death in patients with symptomatic heart failure. However, trials investigating the effects of this drug class in patients following acute myocardial infarction are lacking. METHODS AND RESULTS: In this academic, multicentre, double-blind trial, patients (n = 476) with acute myocardial infarction accompanied by a large creatine kinase elevation (>800 IU/L) were randomly assigned to empagliflozin 10 mg or matching placebo once daily within 72 h of percutaneous coronary intervention. The primary outcome was the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) change over 26 weeks. Secondary outcomes included changes in echocardiographic parameters. Baseline median (interquartile range) NT-proBNP was 1294 (757-2246) pg/mL. NT-proBNP reduction was significantly greater in the empagliflozin group, compared with placebo, being 15% lower [95% confidence interval (CI) -4.4% to -23.6%] after adjusting for baseline NT-proBNP, sex, and diabetes status (P = 0.026). Absolute left-ventricular ejection fraction improvement was significantly greater (1.5%, 95% CI 0.2-2.9%, P = 0.029), mean E/e' reduction was 6.8% (95% CI 1.3-11.3%, P = 0.015) greater, and left-ventricular end-systolic and end-diastolic volumes were lower by 7.5 mL (95% CI 3.4-11.5 mL, P = 0.0003) and 9.7 mL (95% CI 3.7-15.7 mL, P = 0.0015), respectively, in the empagliflozin group, compared with placebo. Seven patients were hospitalized for heart failure (three in the empagliflozin group). Other predefined serious adverse events were rare and did not differ significantly between groups. CONCLUSION: In patients with a recent myocardial infarction, empagliflozin was associated with a significantly greater NT-proBNP reduction over 26 weeks, accompanied by a significant improvement in echocardiographic functional and structural parameters. CLINICALTRIALS.GOV REGISTRATION: NCT03087773.

Reversal of systolic dysfunction in noncompaction and Wolff-Parkinson-White syndrome after accessory pathway ablation.

In a previously healthy asymptomatic 18-year old male, Wolff-Parkinson-White syndrome (WPW) with left ventricular hypertrabeculation/noncompaction (LVHT) and systolic dysfunction was detected. Holter monitoring disclosed multiple long episodes of supraventricular tachycardia with a heart rate of about 110/min. After radiofrequency ablation of an epicardial posteroseptal accessory pathway with ante- and retrograde conduction, systolic function gradually normalized without any pharmacotherapy. After 32 months of follow-up, the patient remains asymptomatic with normal systolic function. WPW-induced tachycardiomyopathy may even occur in asymptomatic patients, who are so adapted to their arrhythmias that they do not recognize them. .

Subcutaneous implanted cardioverter-defibrillator in ventricular noncompaction, coronary artery disease and stroke.

Left ventricular hypertrabeculation/noncompaction (LVHT) is associated with arrhythmias. Guidelines for prevention of sudden cardiac death by implanted cardioverter-defibrillator (ICD) also apply to LVHT-patients. Right ventricular perforation by the ICD-lead is a matter of concern. Subcutaneous ICD (S-ICD) may overcome disadvantages of transvenous ICD in patients without a need for pacing therapy. We report a LVHT-patient with arterial hypertension, hyperlipidemia, coronary artery disease with an anterior-wall myocardial infarction 2004 and stroke without neurological deficits in 2018. Since ejection fraction of 33% remained unchanged despite bisoprolol, sacubitril/valsartan and spironolactone, he was treated with S-ICD for primary prevention of sudden cardiac death.

Improved in-hospital outcome for radial access in a large contemporary cohort of primary percutaneous coronary intervention.

BACKGROUND: Randomised controlled trials have shown diverse results for radial access in patients undergoing primary percutaneous coronary intervention (PPCI). Moreover, it is questionable whether radial access improves outcome in patients with cardiogenic shock undergoing PPCI. We aimed to investigate the outcome according to access site in patients with or without cardiogenic shock, in daily clinical practice. METHODS: For the present analysis we included 9,980 patients undergoing PPCI between 2012 and 2018, registered in the multi-centre, nationwide registry on PCI for myocardial infarction (MI). In-hospital mortality, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE) until discharge were compared between 4,498 patients with radial (45%) and 5,482 patients with femoral (55%) access. RESULTS: Radial compared to femoral access was associated with lower in-hospital mortality (3.5% vs. 7.7%; P<0.01). Multivariable logistic regression analysis confirmed reduced in-hospital mortality [odds ratio (OR) 0.57, 95% confidence interval (CI): 0.43 to 0.75]. Furthermore, MACE (OR 0.60, 95% CI: 0.47 to 0.78) as well as NACE (OR 0.59, 95% CI: 0.46 to 0.75) occurred less frequently in patients with radial access. Interaction analysis with cardiogenic shock showed an effect modification, resulting in lower mortality in PCI via radial access in patients without, but no difference in those with cardiogenic shock (OR 1.78, 95% CI: 1.07 to 2.96). CONCLUSIONS: Radial access for patients with acute MI undergoing PPCI is associated with improved survival in a large contemporary cohort of daily practice. However, this beneficial effect is restricted to hemodynamically stable patients.

Usefulness of Neuromuscular Co-morbidity, Left Bundle Branch Block, and Atrial Fibrillation to Predict the Long-Term Prognosis of Left Ventricular Hypertrabeculation/Noncompaction.

The prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT) is assessed controversially. LVHT is associated with other cardiac abnormalities and with neuromuscular disorders (NMD). Aim of the study was to assess cardiac and neurological findings as predictors of mortality rate in adult LVHT-patients. Included were patients with LVHT diagnosed between 1995 and 2019 in 1 echocardiographic laboratory. Patients underwent a baseline cardiologic examination and were invited for a neurological investigation. In January 2020, their survival status was assessed. End points were death or heart transplantation. LVHT was diagnosed by echocardiography in 310 patients (93 female, aged 53 ± 18 years) with a prevalence of 0.4%/year. A neurologic investigation was performed in 205 patients (67%). A specific NMD was found in 33 (16%), NMD of unknown etiology in 123 (60%) and the neurological investigation was normal in 49 (24%) patients. During follow-up of 84 ± 71 months, 59 patients received electronic devices, 105 patients died, and 6 underwent heart transplantation. The mortality was 4.7%/year, the rate of heart transplantation/death 5%/year. By multivariate analysis, the following parameters were identified to elevate the risk of mortality/heart transplantation: increased age (p = 0.005), inpatient (p = 0.001), presence of a specific NMD (p = 0.0312) or NMD of unknown etiology (p = 0.0365), atrial fibrillation (p = 0.0000), ventricular premature complexes (p = 0.0053), exertional dyspnea (p = 0.0023), left bundle branch block (p = 0.0201), and LVHT of the posterior wall (p = 0.0158). In conclusion, LVHT patients should be systematically investigated neurologically since neurological co-morbidity has a prognostic impact.

Multisystem Myotilinopathy, including Myopathy and Left Ventricular Noncompaction, due to the MYOT Variant c.179C>T.

Left ventricular hypertrabeculation/noncompaction is a myocardial abnormality of unknown etiology/pathogenesis, which is frequently associated with neuromuscular disorders or chromosomal defects. LVHT in association with a MYOT mutation has not been reported. The patient is a 72-year-old male with a history of strabismus in childhood, asymptomatic creatine-kinase elevation since age 42 years, slowly progressive lower limb weakness since age 60 years, slowly progressive dysarthria and dysphagia since age 62 years, and recurrent episodes of arthralgias and myalgias since age 71 years. He also had arterial hypertension, diverticulosis, hyperlipidemia, coronary heart disease, and a hiatal hernia with reflux esophagitis. Clinical exam revealed mild quadruparesis and proximal wasting of the legs. Whole exome sequencing revealed a known variant in the MYOT gene. Muscle biopsy, previously assessed as inclusion body myopathy, was compatible with the genotype after revision. Cardiologic work-up revealed a left anterior hemiblock, mild myocardial thickening, and noncompaction. This case shows that myotilinopathy may manifest as a multisystem disease, including noncompaction.

Reversible myocardial oedema due to acute myocardial infarction as differential diagnosis of cardiac transthyretin amyloidosis.

Using bone-avid radiotracers, cardiac transthyretin (TTR) amyloidosis can be diagnosed by scintigraphy, thus obviating endomyocardial biopsy. Radiotracer accumulation, however, may also be due to other causes. A 68-year-old male with acute myocardial infarction underwent recanalization of the left anterior descending coronary artery (LAD). Postinterventionally, transthoracic echocardiography showed hypokinesia of the septum and anterior wall and a thickened myocardium with granular sparkling appearance. Cardiac amyloidosis was suspected. A 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid whole-body scan 4 days after LAD recanalization showed Perugini 2 myocardial tracer uptake. Monoclonal gammopathy was excluded, and cardiac TTR amyloidosis was diagnosed. Three months later, 99m-Tc-hydroxydiphosphate scan showed no myocardial tracer uptake. Cardiac magnetic resonance imaging revealed late gadolinium enhancement within the LAD supply area. No mutation of the TTR gene was found. Suspicion of amyloidosis should consider not only echocardiography but also history and clinical findings. Myocardial oedema due to reperfusion should be acknowledged as a differential diagnosis for cardiac uptake of bone-avid radiotracers.

Culprit Vessel Only Versus Complete Revascularisation in Patients with ST-Segment Elevation Myocardial Infarction - Should we Stay or Stage?

Multivessel coronary artery disease (MVCAD) is common in patients with ST-elevation myocardial infarction (STEMI), thereby negatively affecting mortality and outcome. Currently there is increasing evidence that complete revascularisation should be considered in haemodynamically stable patients. There are few larger randomised controlled trials available showing a lower risk of major adverse cardiac events after complete revascularisation, mainly driven by a reduction of repeat revascularisation. However, these trials are not adequately powered to show a mortality benefit or reduced risk of myocardial infarction. As there are several possible strategies, the presence of MVCAD often poses a therapeutic dilemma for interventional cardiologists and there is still ongoing debate on when and how to perform complete revascularisation. Pending further trials that may clarify which strategy is best, an individualised approach should be adopted.

In-Hospital Outcome Comparing Bivalirudin to Heparin in Real-World Primary Percutaneous Coronary Intervention.

Randomized controlled trials have shown conflicting results regarding the outcome of bivalirudin in primary percutaneous coronary intervention (PPCI). The aim of this study was to evaluate the in-hospital outcomes of patients receiving heparin or bivalirudin in a real-world setting of PPCI: 7,023 consecutive patients enrolled in the Austrian Acute PCI Registry were included between January 2010 and December 2014. Patients were classified according to the peri-interventional anticoagulation regimen receiving heparin (n = 6430) or bivalirudin (n = 593) with or without GpIIb/IIIa inhibitors (GPIs). In-hospital mortality (odds ratio [OR] 1.13, 95% confidence interval [CI] 0.57 to 2.25, p = 0.72), major adverse cardiovascular events (OR 1.18, 95% CI 0.65 to 2.14, p = 0.59), net adverse clinical events (OR 1.01, 95% CI 0.57 to 1.77, p = 0.99), and TIMI non-coronary artery bypass graft-related major bleeding (OR 0.41, 95% CI 0.09 to 1.86, p = 0.25) were not significantly different between the groups. However, we detected potential effect modifications of anticoagulants on mortality by GPIs (OR 0.12, 95% CI 0.01 to 1.07, p = 0.06) and access site (OR 0.25, 95% CI 0.06 to 1.03, p = 0.06) favoring bivalirudin in femoral access. In conclusion, this large real-world cohort of PPCI, heparin-based anticoagulation showed similar results of short-term mortality compared with bivalirudin. We observed a potential effect modification by additional GPI use and access favoring bivalirudin over heparin in femoral, but not radial, access.

Takotsubo-like syndrome triggered by fludrocortisone overdose for Addison's disease: a case report.

BACKGROUND: Reversible left ventricular dysfunction, also termed Takotsubo cardiomyopathy, is rarely reported in Addison's disease after initiation of hormone replacement therapy. The pathogenesis of this cardiomyopathy is unknown. CASE PRESENTATION: A 41-year-old white woman with a history of autoimmune Hashimoto thyroiditis diagnosed 3 years earlier and acute adrenal insufficiency diagnosed 3 weeks earlier presented with new onset of heart failure New York Heart Association class IV, which had started shortly after initiation of hormone replacement therapy with hydrocortisone 20 mg/day and fludrocortisone 0.3 mg/day. Nine days before admission she had collapsed because of dizziness and had a cerebral concussion and open fracture of her nasal bone, however, no further investigations were carried out at that time. A physical examination revealed leg edema, tachycardia, tachypnea, bilateral basal crepitations, and blood pressure 110/70 mmHg. An electrocardiogram showed sinus tachycardia, low voltage, negative T-waves in V5 and V6 and a corrected QT interval of 590 ms. Echocardiography revealed a reduced left ventricular systolic function with an ejection fraction of 30 %, and septal, apical, and anterior wall akinesia. Cardiac magnetic resonance imaging showed relative enhancement of gadolinium, indicating hyperemia and capillary leakage, and no myocardial scars. Because of the improvement in her cardiac function, lack of cardiovascular risk factors, and lack of signs for ischemia on magnetic resonance imaging, no coronary angiography was carried out. The results of sellar and renal magnetic resonance imaging were normal. Her troponin T was slightly elevated. Bisoprolol and ramipril were started. Her fludrocortisone dose was reduced to 0.05 mg/day. Her electrocardiogram and systolic function, documented by echocardiography and magnetic resonance imaging, normalized within 6 months. CONCLUSIONS: Although we could not exclude coronary artery disease by coronary angiography, her clinical course and instrumental findings suggest Takotsubo cardiomyopathy of the apical type. Fludrocortisone overdosage and increased myocardial vulnerability due to cortisol deficiency might be pathogenetic factors, whereas myocarditis is unlikely. When hormone replacement in patients with Addison's disease is initiated, cardiac function should be monitored by electrocardiogram and echocardiography.

Atrial fibrillation: state of the art.

Atrial fibrillation (AF) is by far the most frequent heart rhythm disorder and is associated with a significantly increased risk of stroke, heart failure and death. Despite improvements in prevention and treatment, the prognosis has not changed significantly. To use new and promising pharmacological and interventional concepts for thromboembolic prophylaxis and treatment of AF, as well as prevention of recurrence, patient compliance has to be improved, physicians have to be trained and experience hast to be gained. A consistently carried 'anticoagulation pass' might be a promising piece of the puzzle.

The wealth of nations and the dissemination of cardiovascular research.

BACKGROUND: This study aimed at understanding whether investigators from less wealthy countries were at a disadvantage in disseminating their research, after accounting for potential differences in research quality and infrastructure. METHODS AND RESULTS: In this bibliometric analysis a representative random selection of 10% (n=1002 studies) of all abstracts submitted to the European Society of Cardiology (ESC) congress 2006 was followed for publication and citation from September 2006 to December 2011. The main variable of interest was the per-capita gross domestic product (GDP) of the country of the principal investigator. Using multivariable models that adjusted for socioeconomic indicators and previously identified markers of research quality, we examined the relationship between per-capita GDP and three study endpoints: Acceptance at the ESC congress, full-text publication, and number of two-year citations. Among 1002 abstracts from 63 countries, per-capita GDP was positively correlated with all three study endpoints. After adjusting for markers of research quality and infrastructure, per-capita GDP remained a strong predictor for acceptance at the ESC congress (adjusted OR for every 10,000 USD increase in per-capita GDP, 1.44; 95% CI, 1.15 to 1.80), full-text publication within 5years (adjusted OR, 1.49; 95% CI, 1.17 to 1.90), and high citation frequency (adjusted OR, 2.30; 95% CI, 1.31 to 4.04). These findings were largely consistent in a subgroup of abstracts of high-quality, prospective clinical trials. CONCLUSION: Investigators in less wealthy countries face challenges to disseminate their research, even after accounting for potential differences in the quality of their work and research infrastructure.

Peripheral blood monocyte Sirt1 expression is reduced in patients with coronary artery disease.

BACKGROUND: Inflammation plays a key role in atherosclerosis. Sirt1 regulates transcription factors involved in inflammatory processes and blunts atherosclerosis in mice. However, its role in humans remains to be defined. This study was therefore designed to investigate the role of Sirt1 in the development of atherosclerosis. METHODS AND RESULTS: 48 male subjects admitted for cardiac catheterization were subdivided into healthy subjects, patients with stable coronary artery disease (CAD), and with acute coronary syndromes (ACS). Monocytes were isolated and Sirt1 mRNA levels were determined. Sirt1 gene expression was higher in healthy subjects as compared to patients with CAD or ACS (P<0.05), respectively. Interestingly, HDL levels correlated positively with Sirt1 expression. Thus, HDL from the three groups was isolated and incubated with THP-1 monocytes to determine the effects of HDL on Sirt1 protein in controlled experimental conditions. HDL from healthy subjects stimulated Sirt1 expression in THP-1 monocytes to a higher degree than HDL from CAD and ACS patients (P<0.05). Paraoxonase-1 (PON-1), a HDL-associated enzyme, showed a reduced activity in HDL isolated from CAD and ACS patients as compared to the controls (P<0.001). CONCLUSIONS: Monocytic Sirt1 expression is reduced in patients with stable CAD and ACS. Experiments on THP-1 monocytes suggest that this effect is HDL-dependent and is mediated by a reduced activity of HDL-associated enzyme PON1.

From abstract to impact in cardiovascular research: factors predicting publication and citation.

AIMS: Through a 4-year follow-up of the abstracts submitted to the European Society of Cardiology Congress in 2006, we aimed at identifying factors predicting high-quality research, appraising the quality of the peer review and editorial processes, and thereby revealing potential ways to improve future research, peer review, and editorial work. METHODS AND RESULTS All abstracts submitted in 2006 were assessed for acceptance, presentation format, and average reviewer rating. Accepted and rejected studies were followed for 4 years. Multivariate regression analyses of a representative selection of 10% of all abstracts (n= 1002) were performed to identify factors predicting acceptance, subsequent publication, and citation. A total of 10 020 abstracts were submitted, 3104 (31%) were accepted for poster, and 701 (7%) for oral presentation. At Congress level, basic research, a patient number ≥ 100, and prospective study design were identified as independent predictors of acceptance. These factors differed from those predicting full-text publication, which included academic affiliation. The single parameter predicting frequent citation was study design with randomized controlled trials reaching the highest citation rates. The publication rate of accepted studies was 38%, whereas only 24% of rejected studies were published. Among published studies, those accepted at the Congress received higher citation rates than rejected ones. CONCLUSIONS: Research of high quality was determined by study design and largely identified at Congress level through blinded peer review. The scientometric follow-up revealed a marked disparity between predictors of full-text publication and those predicting citation or acceptance at the Congress.

Expression of the aging gene p66Shc is increased in peripheral blood monocytes of patients with acute coronary syndrome but not with stable coronary artery disease.

OBJECTIVE: The interplay between oxidative stress and inflammation is crucial in the pathogenesis of atherosclerosis. The adaptor protein p66Shc is implicated in atherogenesis and oxidative stress related responses in animal models of diseases. However, its role in humans remains to be defined. In this study, we hypothesized that expression of p66Shc increases in peripheral blood monocytes of patients affected by acute coronary syndromes (ACS). METHODS: Male subjects aged 59±4 (mean±SD) years admitted for cardiac catheterization were subdivided in three groups: (a) no local stenosis for the control group, (b) at least one stenosis ≥75% in either left, circumflex or right coronary artery for the coronary artery disease (CAD) group or (c) ST-elevation/non-ST-elevation myocardial infarction for the ACS group. Monocytes were isolated from whole blood and p66Shc RNA levels were determined by quantitative real time PCR. RESULTS: p66Shc RNA levels were increased in ACS patients as compared to CAD (p=0.007) and controls (p=0.0249). Furthermore, malondialdehyde (MDA) and C-reactive protein (CRP) were increased in plasma of ACS patients. Levels of MDA correlated positively to p66Shc (r=0.376, p=0.01). Our data demonstrate increased p66Shc levels in monocytes of ACS but not CAD patients. CONCLUSION: This study suggests an involvement of p66Shc in the transition of a stable CAD to an ACS patient. p66Shc was associated with states of increased oxidative stress. Further work is needed to understand whether p66Shc may represent a possible pharmacological target or whether it represents an interesting novel biomarker.

Anti-thymocyte globulin induces neoangiogenesis and preserves cardiac function after experimental myocardial infarction.

RATIONALE: Acute myocardial infarction (AMI) followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries. OBJECTIVE: Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG) was evaluated in this study. METHODS AND RESULTS: AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat) was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01). Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG. CONCLUSIONS: These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI.