Evaluation of systemic inflammation in response to remote ischemic preconditioning in patients undergoing transcatheter aortic valve replacement (TAVR).

BACKGROUND: Systemic inflammation can occur after transcatheter aortic valve replacement (TAVR) and correlates with adverse outcome. The impact of remote ischemic preconditioning (RIPC) on TAVR associated systemic inflammation is unknown and was focus of this study. METHODS: We performed a prospective controlled trial at a single center and included 66 patients treated with remote ischemic preconditioning (RIPC) prior to TAVR, who were matched to a control group by propensity score. RIPC was applied to the upper extremity using a conventional tourniquet. Definition of systemic inflammation was based on leucocyte count, C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), assessed in the first 5 days following the TAVR procedure. Mortality was determined within 6 months after TAVR. RIPC group and matched control group showed comparable baseline characteristics. RESULTS: Systemic inflammation occurred in 66% of all patients after TAVR. Overall, survival after 6 months was significantly reduced in patients with systemic inflammation. RIPC, in comparison to control, did not significantly alter the plasma levels of leucocyte count, CRP, PCT or IL-6 within the first 5 days after TAVR. Furthermore, inflammation associated survival after 6 months was not improved by RIPC. Of all peri-interventional variables assessed, only the amount of the applied contrast agent was connected to the occurrence of systemic inflammation. CONCLUSIONS: Systemic inflammation frequently occurs after TAVR and leads to increased mortality after 6 months. RIPC neither reduces the incidence of systemic inflammation nor improves inflammation associated patient survival within 6 months.

Percutaneous Left Ventricular Assist Device Leads to Heart Rhythm Stabilisation in Cardiogenic Shock: Results from the Dresden Impella Registry.

BACKGROUND: Severe heart rhythm disturbances (SHRDs) occur regularly in cardiogenic shock (CS). Percutaneous left ventricular assist devices (pLVADs) can actively unload the left ventricle (LV), decreasing left ventricular end-diastolic pressure and wall tension, which are suspected parameters for the induction and maintenance of arrhythmias. The aim of this study was to describe effects of LV unloading on SHRD. METHOD: In the Dresden Impella Registry, 97 patients received an Impella CP in refractory CS. Of them, 19 had SHRDs, which were not stopped by common therapeutic strategies such as electrical defibrillation or antiarrhythmic drugs. They were only stopped after implantation of a micro-axial heart pump. This phenomenon was referred to as heart rhythm stabilisation (HRS). Clinical outcome and laboratory parameters were assessed and risk factors for the occurrence of HRS were identified. RESULTS: All 19 patients with refractory SHRD terminated immediately into a stable heart rhythm after insertion of the micro-axial heart pump. In 37% no additional defibrillation was needed. Of the patients with HRS, CS was mostly caused by myocardial infarction (68%). Resuscitation before pLVAD was performed in 89% for more than 30 minutes. Patients with HRS were resuscitated more frequently and for a longer duration than patients without HRS. After HRS, the serum lactate and norepinephrine dosage decreased in the first 12 hours, whereas left ventricular ejection fraction increased by 95%. CONCLUSIONS: Left ventricular unloading in patients with CS seems to be an option for treating patients with sustained life-threatening tachycardia, who are refractory to common treatment.

Regulation of circulating chromogranin B levels in heart failure.

BACKGROUND: Chromogranin B (CGB) regulates B-type natriuretic peptide (BNP) production. Circulating CGB levels are elevated in heart failure (HF) animal models and HF patients, but also increase in healthy individuals in response to physical activity. Therefore, CGB seems to integrate information from myocardial stress and systemic neuro-endocrine activation. Substantial gaps remain in our understanding of CGB regulation in HF. METHODS AND RESULTS: We conducted a retrospective registry study including 372 patients. CGB and N-terminal pro-BNP (NT-proBNP) plasma levels were assessed in acute HF and chronic valvular HF patients and controls. CGB levels were significantly increased in acute HF and chronic valvular HF, but significantly higher in the latter. Patients in chronic valvular HF with severe mitral regurgitation (cHF-MR) showed significantly higher CGB levels than patients in chronic valvular HF with severe aortic stenosis. CGB levels progressively increased with worsening NYHA functional status and were moderately correlated to NT-proBNP, but independent of left ventricular (LV) ejection fraction (LVEF), LV mass, age and body weight. Finally, cHF-MR patients showed significant reductions of CGB levels after interventional mitral valve repair. CONCLUSION: CGB is a promising emerging biomarker in HF patients with unique potential to integrate information from myocardial stress and neuro-endocrine activation.

Reduction of atrial fibrillation burden by pulmonary vein isolation leads to a decrease of CD11b expression on inflammatory cells.

Aims: It is hypothesized that inflammation could promote structural and electrical remodelling processes in atrial fibrillation (AF). Atrial infiltration of monocytes and granulocytes has been shown to be dependent on CD11b expression. The aim of this study was to investigate whether treatment of AF by pulmonary vein isolation (PVI) may lead to reduced inflammation, as indicated by a decrease of CD11b expression on monocytes and granulocytes. Methods and results: Flow-cytometric quantification analysis and determination of systemic inflammatory markers of peripheral blood were performed in 75 patients undergoing PVI 1 day before and 6 months after PVI. The extent of activation of monocytes and granulocytes was measured by quantifying the cell adhesion molecule CD11b. The mean expression of CD11b on monocytes (20.9 ± 2.5 vs. 10.2 ± 1.4; P < 0.001) and granulocytes (13.9 ± 1.6 vs. 6.8 ± 0.5; P < 0.001), as well as the relative count of CD11b-positive monocytes (P < 0.05) and CD11b-positive granulocytes (P < 0.01) were significantly reduced when comparing the identical patients before and 6 months after PVI. Systemic inflammatory parameters showed only a declining tendency after 6 months. Patients with unsuccessful PVI and ongoing AF on the day of follow-up showed no decrease in CD11b expression. Conclusions: A significant reduction of CD11b expression on monocytes and granulocytes, as a sign of reduced cellular inflammation, was achieved by treatment of AF using PVI. These data strongly support that AF is not only a consequence of but also a cause for inflammatory processes, which, in turn, may contribute to atrial remodelling.

Three-dimensional transoesophageal echocardiography is crucial for valid assessment of mitral valve leaflet morphology in severe mitral regurgitation prior to interventional repair.

BACKGROUND: Interventional mitral valve (MV) repair of severe symptomatic mitral regurgitation (MR) is a therapeutic option in high-risk surgical or inoperable patients. Assessment of the MV remains a crucial part of pre-interventional screening. Three-dimensional transoesophageal echocardiography (3D-TOE) may compensate for well-known pitfalls that occur in 2D-TOE. PURPOSE: We investigated whether the functional length of the central segments of the posterior and anterior MV leaflets (PML-P2 and AML-A2) is more reliably determined by 3D-TOE full volume datasets (3D-MPR) or orthogonal biplane-imaging (Xplane) when compared to 2D-TOE. METHODS AND RESULTS: Between February 2014 and August 2015, 265 consecutive patients with moderate to severe symptomatic MR were screened. Seventy patients were judged suitable for interventional MV repair by the in-house Heart-Team. Eventually, 59 patients remained for data analysis. Inter-observer variability was lowest in 3D-MPR followed by Xplane (r = 0.92 and 0.90, p < .001 for both) and highest in Mplane (r = 0.82, p < .001). Mean functional PML-P2 lengths were similar in Xplane (12.6 ± 1.7 mm) and 3D-MPR (12.1 ± 2.0 mm), however, significantly different in 2D-TOE (10.0 ± 2.1 mm, p < .001). 2D-TOE underestimated PML-P2 length with a bias of -2.5 mm compared to Xplane and -1.95 mm compared to 3D-MPR. In contrast, functional AML-A2 length was determined similar across all methods. CONCLUSIONS: Our results demonstrate the superiority of 3D-TOE over 2D-TOE for accurate MV assessment in MR, especially for the determination of the functional PML length. Erroneous MV leaflet assessment may result in inadequate therapy restriction if the MV is deemed not suitable for interventional repair.

Experience With the Wearable Cardioverter-Defibrillator in Patients at High Risk for Sudden Cardiac Death.

BACKGROUND: This study evaluated the wearable cardioverter-defibrillator (WCD) for use and effectiveness in preventing sudden death caused by ventricular tachyarrhythmia or fibrillation. METHODS: From April 2010 through October 2013, 6043 German WCD patients (median age, 57 years; male, 78.5%) were recruited from 404 German centers. Deidentified German patient data were used for a retrospective, nonrandomized analysis. RESULTS: Ninety-four patients (1.6%) were treated by the WCD in response to ventricular tachyarrhythmia/fibrillation. The incidence rate was 8.4 (95% confidence interval, 6.8-10.2) per 100 patient-years. Patients with implantable cardioverter-defibrillator explantation had an incidence rate of 19.3 (95% confidence interval, 12.2-29.0) per 100 patient-years. In contrast, an incidence rate of 8.2 (95% confidence interval, 6.4-10.3) was observed in the remaining cardiac diagnosis groups, including dilated cardiomyopathy, myocarditis, and ischemic and nonischemic cardiomyopathies. Among 120 shocked patients, 112 (93%) survived 24 hours after treatment, whereas asystole was observed in 2 patients (0.03%) with 1 resulting death. CONCLUSIONS: This large cohort represents the first nationwide evaluation of WCD use in patients outside the US healthcare system and confirms the overall value of the WCD in German treatment pathways.

Association of platelet activation markers with recurrence of atrial fibrillation after pulmonary vein isolation.

Atrial fibrillation (AF) is known to cause platelet activation. AF and its degree of thrombogenesis could be associated with monocyte-platelet aggregates (MPAs). We investigated on whether the content of MPAs or other platelet activation markers is associated with the recurrence of AF after pulmonary vein isolation (PVI). A total of 73 patients with symptomatic AF underwent PVI. After 6 months, all patients were evaluated for episodes of AF recurrence. At the same time, flow-cytometric quantification analyses were performed to determine the content of MPAs. Further platelet activation parameters were detected by using either cytometric bead arrays or quantitative immunological determination. Patients with recurrent AF (n = 20) compared to individuals without AF relapse (n = 53) were associated with an increased content of MPAs (43 ± 3% vs. 33 ± 2%, p = 0.004), as well as an increased CD41 expression on monocytes (191 ± 20 vs. 113 ± 6, p = 0.001). The level of the soluble platelet activation markers such as D-dimer, sCD40L, and sP-selectin did not differ between these groups. The content of MPAs correlated weakly with the level of sCD40L (r = 0.26, p = 0.03), but not with sP-selectin and D-dimer, whereas sP-selectin and sCD40L correlated with each other (r = 0.38, p = 0.001). Only the cellular marker of platelet activation, the content of MPAs, was increased in patients with recurrent AF after PVI. In contrast, soluble markers remained unaltered. These data indicate a distinct mechanism and level of platelet activation in AF. The clinical relevance of MPAs in identifying AF recurrence or in guiding the therapy with anticoagulants remains to be elucidated.

Evaluation of heart involvement in calpainopathy (LGMD2A) using cardiovascular magnetic resonance.

INTRODUCTION: Cardiac dysfunction occurs in several forms of limb girdle muscular dystrophy (LGMD). The aim of this study was to investigate cardiac involvement in calpainopathy (LGMD2A). METHODS: Cardiovascular evaluation was performed in 10 patients with genetically verified LGMD2A by echocardiography, 3 Tesla - cardiovascular magnetic resonance, 24-h electrocardiography recordings with heart rate variability (HRV) analysis, and 24-h blood pressure recordings. RESULTS: No patient with calpainopathy showed impairment of left or right ventricular function. One patient had a small amount (2% of left ventricle mass) of late gadolinium enhancement. HRV analysis revealed no significant difference compared with external reference data. CONCLUSIONS: The main finding of this study is the lack of cardiac involvement in patients with calpainopathy. Cardiac involvement was not found, even in individuals with advanced age and greater disease severity. Furthermore, we did not observe an overall reduction of cardiac autonomic regulation in calpainopathy.

Transient global amnesia and broken heart syndrome: two faces of one pathology.

We present a case of a 57-year-old female patient with transient global amnesia, who later developed broken heart syndrome also known as takotsubo cardiomyopathy. The present case underlines that co-occurrence of both pathologies might still be an under-recognized clinical problem.

Soluble ST2 and myocardial fibrosis in 3T cardiac magnetic resonance.

OBJECTIVE: The soluble form of ST2 (sST2) is a novel laboratory parameter for cardiac risk prediction, and over the past years, several studies have tried to evaluate its utility, especially in the management of heart failure. We investigated whether increased serum levels of sST2 show a characteristic pathomorphologic pattern in 3-Tesla cardiac magnetic resonance imaging (CMRI). METHODS: One hundred and fifty-six patients referred to 3T CMRI due to suspected coronary artery disease (CAD) or myocarditis were prospectively enrolled in the study. Ninety patients were diagnosed with CAD, 22 patients with myocarditis, and 44 patients, who constituted the reference group, showed no pathologic CMRI pattern. RESULTS: There was no significant difference between the sST2 values for patients in the reference group and patients with CAD or myocarditis. The sST2 concentration showed a weak correlation with the NYHA functional class (P = 0.002, r = 0.22), but correlation of sST2 and LGE, left ventricular parameters, and LVEF could not be seen. In contrast NT-proBNP was positively correlated to left ventricular parameters, LGE, and NYHA class function (P < 0.05). Additionally, it showed an inverse relationship to LVEF (P < 0.001, r = - 0.42). CONCLUSIONS: Soluble ST2 is not able to detect myocardial scar and should not be used alone as a parameter for detection of inflammation and myocardial scar formation.

3-T magnetic resonance for determination of aortic valve area: a comparison to echocardiography.

OBJECTIVES: For evaluation of aortic valve area (AVA), transthoracic echocardiography (TTE) is the method of choice. Cardiac magnetic resonance (CMR) at 1.5-Tesla is an alternative. The aim of the study was to check whether quantification of whole range of AVA without severe aortic stenosis is possible and reliable in higher magnetic field strength, and also including a comparison to TTE. METHODS: In 3-T CMR phase contrast sequences were assessed above aortic valve and left ventricular output tract. AVA was calculated using the continuity equation. Planimetric analysis of AVA was performed in magnitude images. TTE was used as reference method for graduation of AVA. RESULTS: Totally 48 patients (64 ± 18 years) without severe aortic valve stenosis were prospectively enrolled. In CMR planimetric AVA was 2.5 ± 1.3 cm(2) and calculated AVA 2.4 ± 1.3 cm(2), whereas AVA in TTE was 1.9 ± 1.1 cm(2). Planimetric and calculated AVA in CMR and also AVA in CMR and TTE showed good correlation (r = 0.97, 0.92, respectively). Bland-Altman analysis demonstrated no signs of over- or underestimation. Inter- and intraobserver variabilities were low. DISCUSSION: Determination of AVA using 3-T CMR is possible using direct planimetry and continuity equation. CMR is the alternative first choice method in cases with discrepant or insufficient echocardiographic results.

Aortic stenosis: right and left ventricular function in the early postprocedural phase. Comparison between transcatheter and surgical aortic valve implantation.

BACKGROUND: While impact of surgical aortic valve replacement (SAVR) on the function of the right and left ventricle (RV, LV) has been studied extensively, the objective of this study was to compare the two different transcatheter approaches, transfemoral vs. transapical aortic valve implantation (tf-AVI, ta-AVI) and SAVR with respect to postoperative recovery of RV and LV function in patients with severe aortic stenosis. METHODS AND RESULTS: Conventional echocardiographic studies were performed before and after the procedure (< 8 days) in 74 consecutive patients undergoing tf-AVI, 88 with ta-AVI and 63 surgically treated patients. Post procedure, a marked deterioration in the tricuspid annular plane systolic excursion (TAPSE) was seen after SAVR (23.7 +/- 4 mm vs. 15.6 +/- 2.9 mm, P > 0.001) and ta-AVI (21.1 +/- 4.7 mm vs. 19.1 +/- 4.7 mm, P = 0.02), while TAPSE remained unchanged in the tf-AVI group (21.7 +/- 5 mm vs. 22.1 +/- 4.9 mm, P = 0.38). Additionally, a significant drop of the visually estimated right ventricular ejection fraction in the SAVR and ta-AVI group compared to tf-AVI could be seen (P < 0.001, P = 0.003, respectively) Among patients with a pre-existing reduced LV-function, despite similar baseline LVEF (38.5 +/- 7.1% vs. 37.4 +/- 5.6, P = 0.8), tf-AVI patients had better recovery of LVEF compared with ta-AVI (ALVEF 7.2 +/- 8% vs. 1.6 +/- 9.3%, P = 0.038). CONCLUSION: Our study underlines the less invasive nature of tf-AVI, causing less intraoperative trauma and pericardial adhesions to the heart. Given that acute RV failure after cardiac surgery remains a major cause of morbidity and mortality, the results of the present study suggest that in high-risk patients, TAVI and in particular tf-AVI could be favoured over SAVR in regard to a RV dysfunction.

Simple periprocedural precautions to reduce Doppler microembolic signals during AF ablation.

BACKGROUND: Doppler microembolic signals (MES) occur during atrial fibrillation ablation despite of permanent flushed transseptal sheaths, frequent controls of periprocedural coagulation status and the use of irrigated ablation catheters PURPOSE: To investigate the number and type of MES depending on the procedure time, prespecified procedure steps, the activated clotting time (ACT) during the ablation procedure and the catheter contact force. METHODS: In a prospective trial, 53 consecutive atrial fibrillation patients underwent pulmonary vein isolation by super-irrigated "point-by-point" ablation. All patients underwent a periinterventional, continuous transcranial Doppler examination (TCD) of the bilateral middle cerebral arteries during the complete ablation procedure. RESULTS: An average of 686±226 microembolic signals were detected by permanent transcranial Doppler. Thereby, 569±208 signals were differentiated as gaseous and 117±31 as solid MES. The number of MES with regard to defined procedure steps were as follows: gaseous: [transseptal puncture, 26 ± 28; sheath flushing, 24±12; catheter change, 21±11; angiography, 101±28; mapping, 9±9; ablation, 439±192; protamine administration, 0±0]; solid: [transseptal puncture, 8±8; sheath flushing, 9±5; catheter replacement, 6±6; angiography, not measurable; mapping, 2±5; ablation, 41±22; protamine administration, 0±0]. Significantly less MES occurred with shorter procedure time, higher ACT and the use of tissue contact force monitoring. CONCLUSION: The current study demonstrates that during atrial fibrillation ablation using irrigated, "point-by-point" RF ablation, masses of microembolic signals are detected in transcranial ultrasound especially in the period of RF current application. The number of MES depends on the total procedure time and the reached ACT during ablation. The use of contact force monitoring might reduce MES during RF ablation.

Myocardial strain analysis using cardiac magnetic resonance in patients with calpainopathy.

BACKGROUND: Limb-girdle muscular dystrophy (LGMD) is a genetically and clinically heterogeneous group of rare muscular dystrophies. Subtype 2A (LGMD2A) also known as "calpainopathy" is an inherited autosomal recessive gene defect. Cardiac dysfunction is common in several forms of LGMD. Cardiac involvement in LGMD2A, however, is not clear. The aim of this study was to perform cardiac magnetic resonance (CMR)-based strain analysis in LGMD2A patients, as this is a diagnostic parameter of subclinical cardiac involvement and a powerful independent predictor of mortality. We conducted the largest prospective cardiac magnetic resonance study to date, including 11 genetically verified LGMD2A patients and 11 age- and sex-matched control subjects and performed CMR-based strain analysis of the left and right ventricles. RESULTS: Left and right global longitudinal strain (GLS) were not significantly different between the two groups and within normal reference ranges (left ventricle: control - 21.8 (5.1) % vs. patients - 22.3 (3.2) %, p = 0.38; right ventricle: control - 26.3 (7.2) % vs. patients - 26.8 (5.8) %, p = 0.85). Also, global circumferential and radial strains did not significantly differ between the two groups (p = 0.95 and p = 0.86, respectively). LGMD2A patients did not show relevant amounts of late gadolinium enhancement (LGE) or malignant ventricular arrhythmias. CONCLUSIONS: No evidence of even subtle cardiac dysfunction is evident form CMR-based strain analysis in LGMD2A patients. Malignant ventricular arrhythmias were not detected. Thus, in case of non-pathological initial echocardiographic and electrocardiographic examination, a less frequent or even no cardiac follow-up may be acceptable in these patients. However, if there are signs and symptoms that suggest an underlying cardiac condition (e.g. palpitations, angina, shortness of breath), this approach needs to be individualized to account for the unknown.

Comparison of uninterrupted direct oral anticoagulation with vitamin-K antagonists during AF-ablation in the clinical routine. A single center register.

BACKGROUND: Uninterrupted direct oral anticoagulation (DOAC) in AF-ablation is recommended, proven by randomized trials. The outcome and the periinterventional differences between DOACs and VKA in the real world clinical practice are discussed controversial. HYPOTHESIS: To investigate efficiency and safety of uninterrupted DOAC therapy compared to VKA during AF-Ablation in real world setting with a focus on periinterventional heparin dosage.

Evaluation of Myocardial Strain Using Cardiac Magnetic Resonance in Patients with Wilson's Disease.

(1) Background: Wilson's disease (WD) is an inherited autosomal recessive disorder with the excessive deposition of copper into different organs, including the heart. Previous studies showed structural cardiac changes even in patients with no signs of heart failure. The aim of this study was to perform cardiac magnetic resonance-based strain analysis in WD patients, as it is a powerful independent predictor of mortality. (2) Methods: We conducted a prospective cardiac magnetic resonance study that included 61 patients and 61 age and sex-matched controls, and performed strain analysis of the left and right ventricle. (3) Results: Left ventricular global longitudinal strain (GLS) as a prognostic marker of increased mortality was not altered (control -22.8 (4.8) % vs. WD patients -21.8 (5.1) %, p = 0.124). However, 4 of the 61 patients had a markedly reduced GLS. Global circumferential strain did not significantly differ between the groups either (p = 0.534). WD patients had significantly reduced global radial strain (p = 0.002). Right ventricular GLS was also significantly reduced in WD patients (p = 0.01). (4) Conclusions: Strain analysis revealed functional impairment of the left and right ventricle in a small number of patients as a potential early sign of cardiac manifestation in asymptomatic WD patients.

Cardiac manifestation is evident in chorea-acanthocytosis but different from McLeod syndrome.

INTRODUCTION: We aimed to study the various cardiac manifestations of the two core neuroacanthocytosis (NA) syndromes, namely chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS). So far, cardiac involvement has been described as specific feature only for MLS. METHODS: We studied six patients with ChAc (mean age 44.5 years, five men, one woman) and six patients with MLS (mean age 57.1 years, all men). Cardiac evaluation included echocardiography and/or cardiac magnetic resonance imaging (cardiac MRI), 24-h ECG-recording and examination of cardiac biomarkers. RESULTS: Cardiac involvement of ChAc was found in four of six patients. Two patients showed mildly reduced left ventricular ejection fraction (LVEF), two other patients mild to moderate left ventricular (LV) dilatation. Neither an increase in ventricular ectopic beats nor ventricular tachycardia were evident in ChAc. Four of five MLS patients showed left ventricle dilatation and reduced left ventricular ejection fraction (LVEF). Two of these, in addition, had critical ventricular tachycardia. High sensitive troponin T was elevated in all patients, for whom data were available (n = 10). In contrast, elevation of high sensitive troponin I was found in one of six ChAc and one of two MLS patients. CONCLUSION: For the first time, we reveal cardiac involvement in a cohort of six ChAc patients, while the risk to develop heart failure seems lower than in MLS. Our study confirms the malignant nature of MLS in terms of ventricular arrhythmias and progression to advanced heart failure. Herein, we define disease-specific recommendations for cardiac assessment in both conditions.

Spatio-temporal regulation of calpain activity after experimental myocardial infarction in vivo.

BACKGROUND: Calpains are calcium activated cysteine proteases that play a pivotal role in the pathophysiology of cardiac remodeling. METHODS: Here, we performed left anterior descending coronary artery ligation in rats as a model for ischemic systolic heart failure and examined the time- and region-specific regulation of calpain-1 and calpain-2 in the left ventricular myocardium. RESULTS: Following anterior wall myocardial infarction, calpain activity was significantly increased restricted to the ischemic anterior area at days 1, 5 and 14. No changes in calpain activity at neither time point were detected in the borderzone and remote posterior area of the left ventricle. Of note, calpain activity in the infarcted anterior myocardium was regulated differentially in the acute vs. subacute and chronic phase. In the acute phase, calpain translocation to the plasma membrane and attenuation of the expression of its endogenous inhibitor, calpastatin, were identified as the driving forces. In the subacute and chronic phase, calpain activity was regulated at the level of protein expression that was shown to be essentially independent of transcriptional activity. CONCLUSIONS: We conclude that myocardial infarction leads to a distinct calpain regulation pattern in the left ventricular myocardium that is region specific and time dependent. Considering the results from our previous studies, a spatio-temporal interaction between calpains and calcium dependent natriuretic peptide production in the infarcted myocardium is possible. GENERAL SIGNIFICANCE: Our results shed more light in the differential regulation of calpain activity in the myocardium and might aid in the development of targeted post-infarct and/or heart failure therapeutics.