Search

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. Methods: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score–matched cohort. Results: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63–0.98]; P =0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site–related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). Conclusions: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4–8%) as well as in low-risk patients (STS-Score

Background Cardiogenic shock (CS) in patients (pts) with acute ST elevation myocardial infarction (STEMI) is the strongest predictor of hospital mortality. Radial in contrast to femoral access in STEMI pts might be associated with a lower mortality. However, little is known on radial access in CS pts. Methods We retrospectively analysed all STEMI pts between 2009 and 2015 who sufferend from CS and who were included into the ALKK PCI registry. Pts treated via a radial access were compared to those treated via a femoral access. Results Between 2009 and 2015 23796 STEMI pts were included in the registry. 1763 (7.4%) of pts were in CS. The proportion of radial access was 6.6%: in 2009 4.0% and in 2015 19.6%, p for trend Conclusions Radial access was only used in 6.6% of STEMI pts presenting in CS. However, a significant increase in the use of radial access was observed over time (2009: 4%, 2015 19.6%, p Funding Acknowledgement Type of funding source: None

Aims Left ventricular (LV) dysfunction in viral myocarditis is attributed to myocardial inflammation and fibrosis, inducing acute and long‐time cardiac damage. Interventions are not established. On the basis of the link between inflammation, fibrosis, aldosterone, and extracellular matrix regulation, we aimed to investigate the effect of an early intervention with the mineralocorticoid receptor antagonist (MRA) eplerenone on cardiac remodelling in a murine model of persistent coxsackievirus B3 (CVB3)‐induced myocarditis. Methods and results SWR/J mice were infected with 5 × 104 plaque‐forming units of CVB3 (Nancy strain) and daily treated either with eplerenone (200 mg/kg body weight) or with placebo starting from Day 1. At Day 8 or 28 post infection, mice were haemodynamically characterized and subsequently sacrificed for immunohistological and molecular biology analyses. Eplerenone did not influence CVB3 load. Already at Day 8, 1.8‐fold (P

Iron deficiency (ID) has been recognized as a relevant comorbidity in heart failure with reduced ejection fraction (HFrEF); however, study data have shown that diagnostic and therapeutic efforts on ID are primarily performed in patients with anemia. The RAID-HF registry investigated consecutive patients with ID and HFrEF in 11 heart centers in Germany and Switzerland. The present analysis focuses on 1-year follow-up data in patients with versus without anemia. In 505 patients with HFrEF and ID and 418 patients with HFrEF without ID 1-year follow-up was performed. Patients with ID had a higher long-term mortality compared to those without ID (19.5% vs. 13.7%, p = 0.02) and reported a lower quality of life. Only a minority of patients with ID (9.3%) received iron supplementation during long-term course, just 4.7% intravenously. Anemia was associated with an elevated mortality whereas ID versus no ID did not predict mortality in anemic patients (log-rank p = 0.78). However, in patients without anemia ID versus no ID predicted mortality (log-rank p = 0.002). In the adjusted analysis a significant interaction remained, with ID being a significant predictor of 1-year mortality in patients without anemia (HR 2.15, 95% CI 1.12–3.78), but not in anemic patients (HR 0.99, 95% CI 0.65–1.49). RAID-HF demonstrates the impact of ID on long-term mortality and quality of life in patients with HFrEF and reveals an underuse of iron supplementation in current clinical practice. Particularly in patients without anemia the diagnosis of ID is of clinical relevance to identify patients at higher mortality risk.

Background Veno-arterial extracorporeal membrane oxygenation therapy (VA-ECMO) is increasingly used for treatment of severe cardiogenic shock, although it causes an increase in left ventricular (LV) afterload and might therefore hamper myocardial recovery. Recently, the addition of catheter-based left ventricular assist device (cLVAD) on top of VA-ECMO has been used to unload the LV and to improve outcome measures. However, there is limited data on predictors of outcome in this high-risk population. Aim The aim of this study was to evaluate predictors of 30-day survival in a multicentre cohort of severe cardiogenic shock patients treated with cLVADon top of VA-ECMO. Material and methods We report on consecutive patients from six tertiary care centers being treated with cLVAD in addition to VA-ECMO for treatment of cardiogenic shock. The primary endpoint is 30-day all-cause mortality. To identify predictors of the primary endpoint, multivariate analysis using an “elastic net” variable selection algorithm was done after imputation of missing variables. Results A total of 220 patients treated with cLVAD on top of VA-ECMO were included in the analysis. Of these, 79.1% were male with a median age of 55.5 (25thpercentile 48.0, 75thpercentile 65.6) years. In 60.5% of the patients, acute myocardial infarction was the underlying cause of cardiogenic shock and in 44.6% VA-ECMO was used for refractory cardiac arrest (eCPR). In the multivariable analysis, the following baseline parameters were significantly associated with the primary endpoint: Age (odds ratio of 1.68 per standard deviation), duration of cardiopulmonary resuscitation (OR 2.08 per SD), lactate (OR 1.04 per SD) and time from onset of shock to VA-ECMO (OR 1.30 per SD). Conclusion and outlook In this large-scale multicentre analysis of severe cardiogenic shock patients treated with VA-ECMO plus additional cLVAD unloading, age, duration of cardiopulmonary resuscitation, lactate and time from onset of shock to VA-ECMO were significantly associated with 30-day all-cause mortality. To further investigate this topic, we will evaluate predictors of outcome in distinct patient populations such as acute myocardial infarction vs. acute heart failure and patients without vs. patients with prior cardiopulmonary association.

Background: Percutaneous mechanical circulatory support devices are increasingly used in acute myocardial infarction complicated by cardiogenic shock (AMI-CS), despite limited evidence for their effectiveness. The aim of this study was to evaluate outcomes associated with use of the Impella device compared with intra-aortic balloon pump (IABP) and medical treatment in patients with AMI-CS. Methods: Data of patients with AMI-CS treated with the Impella device at European tertiary care hospitals were collected retrospectively. All patients underwent early revascularization and received optimal medical treatment. Using IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial inclusion and exclusion criteria, 372 patients were identified and included in this analysis. These patients were matched to 600 patients from the IABP-SHOCK II trial. The following baseline criteria were used as matching parameters: age, sex, mechanical ventilation, ejection fraction, prior cardiopulmonary resuscitation, and lactate. Primary end point was 30-day all-cause mortality. Results: In total, 237 patients treated with an Impella could be matched to 237 patients from the IABP-SHOCK II trial. Baseline parameters were similarly distributed after matching. There was no significant difference in 30-day all-cause mortality (48.5% versus 46.4%, P =0.64). Severe or life-threatening bleeding (8.5% versus 3.0%, P P =0.01) occurred significantly more often in the Impella group. Limiting the analysis to IABP-treated patients as a control group did not change the results. Conclusions: In this retrospective analysis of patients with AMI-CS, the use of an Impella device was not associated with lower 30-day mortality compared with matched patients from the IABP-SHOCK II trial treated with an IABP or medical therapy. To further evaluate this, a large randomized trial is warranted to determine the effect of the Impella device on outcome in patients with AMI-CS. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03313687.

The DANISH trial raised doubts about the effectiveness of primary prevention of sudden cardiac death by ICD implantation among patients with non-ischemic heart failure. We sought to analyse data from the EVITA-HF registry to give an answer from real-world registry data to the DANISH trial. 1804 patients were identified from the EVITA-HF registry with chronic heart failure (CHF) due to ischemic or dilated heart disease and reduced left ventricular ejection fraction of ≤ 35%. The patients were divided into two groups: Patients with newly implanted cardioverter–defibrillator (ICD group; mean age 66 ± 12 years, 77% male) and without ICD (no-ICD group; mean age 66 ± 14 years, 77% male). The subgroups were compared with regard to mortality and predictive parameters affecting survival. Cardiovascular risk factors were similar among patients in the non-ICD group (n = 1473) compared to ICD group (n = 331). After 1-year follow-up patients with ischemic heart disease showed a significant improved survival in the ICD group compared to non-ICD group [92.1% vs. 80.6%, HR 0.37 (0.22–0.62)]. Patients with non-ischemic cardiomyopathy did not show a difference with regard to survival between the ICD and the non-ICD group [93.7% vs. 93.1%, HR 0.92 (0.43–1.97)]. The data were stable in a Cox-regression model. In a real-world setting, no benefit was evident for patients with non-ischemic cardiomyopathy and reduced left ventricular ejection fraction by adding ICD therapy in a short-term follow-up of 12 months in contrast to patients with ischemic cardiomyopathy.

Chronic viral infections of the heart are considered one antecedent event leading to progressive dysfunction of the myocardium, often with an impaired prognosis due to a virus- or immune-mediated myocardial injury. Symptomatic treatment does not influence the viral cause of heart failure, and the effect of antiviral treatment has not been determined, yet.In this phase II study 143 patients with symptoms of heart failure and biopsy-based confirmation of the enterovirus (EV), adenovirus, and/or parvovirus B19 genomes in their myocardial tissue were randomly assigned to double-blind treatment, and received either placebo (n = 48) or 4 × 10(6) (n = 49) and 8 × 10(6) IU (n = 46) interferon beta-1b (IFN-β-1b) for 24 weeks, in addition to standard heart failure treatment. Patients with active myocarditis or other specific causes of heart failure were excluded. Compared to placebo, virus elimination and/or virus load reduction was higher in the IFN-β-1b groups (odds ratio 2.33, p = 0.048), similarly in both interferon groups and both strata. IFN-β-1b treatment was associated with favourable effects on NYHA functional class (p = 0.013 at follow-up week 12), improvement in quality of life (Minnesota Heart Failure score; p = 0.032 at follow-up week 24) and patient global assessment (follow-up week 12 to follow-up week 24; p = 0.039). The frequency of adverse cardiac events was not higher in the IFN-β-1b groups compared to the placebo group.Immunomodulatory IFN-β-1b treatment is a well-tolerated and safe treatment option, leading to effective virus clearance or reduction of the virus load in patients with chronic viral cardiomyopathy. Favourable clinical effects assess quality of life, NYHA functional class, and patient global assessment. ClinicalTrials.gov identifier: NCT001185250.

Aims Oesophagogastroduodenoscopy (OGD) after catheter ablation (CA) of atrial fibrillation (AF) revealed a high rate of procedure related oesophageal lesions. We hypothesized that magnetically guided CA with careful radiofrequency energy titration at the posterior left atrial (LA) wall limits the incidence of oesophageal tissue damage. Methods and results As a part of the prospective "Remote MAGNetic catheter Ablation for Atrial Fibrillation" (MAGNA-AF) registry, 251 out of 266 consecutive patients underwent OGD after magnetically guided single-CA for AF. All detected pathologies were analysed. Simultaneous pacing and ablation from the tip of the magnetically guided catheter was found to be a safe and feasible method for energy titration. Post-interventional OGD documented midoesophageal tissue damage in four (1.6%) patients. Although a thermal origin of these injuries must be discussed, none of them was located at the anterior oesophageal wall. Risk factors for midoesophageal lesions were female gender and concomitant acetylsalicylic acid (ASA) treatment. Mechanical lesions in 16 patients were attributed to periprocedural transoesophageal echocardiography (TOE). There was no atrio-oesophageal fistula (AOF). Five hundred and one incidental pathologies were found endoscopically, most frequent axial oesophageal herniation (71%), oesophagitis (22%), and gastritis (57%). Conclusion Magnetically guided CA for AF with careful energy titration at the posterior LA wall and no oesophageal temperature monitoring is not associated with an increased incidence of oesophageal thermal injury. The routine use of periprocedural TOE may cause a low rate of mechanical oesophageal lesions but reliably prevents major complications like transient ischaemic attack, stroke, or cardiac tamponade. An observed high prevalence of upper digestive system inflammation (63%) may further support the recommendation for a routine post-interventional treatment with a proton-pump-inhibitor.

Cardiomyopathies are complex diseases of multifactorial pathogenesis and have a high morbidity and mortality. Over the past decades, several revisions of classifications and definitions of cardiomyopathies have been proposed, primarily focusing on the phenotypic characterization of cardiomyopathies. The MOGE(S) classification system published in 2013 encompasses the classification of rapidly growing knowledge on genetic mutations, acquired causes (i.e., intramyocardial inflammation, viral infections), and further conditions involved in the induction of cardiomyopathies (e.g., storage diseases, toxicity). It is based on five attributes, including morphofunctional characteristics (M), organ involvement (O), genetic or familial inheritance pattern (G), etiological annotation (E), and optional information about the heart failure functional status (S). This review summarizes the development, the cornerstones of the MOGE(S) classification, and the published data on the clinical relevance of the MOGE(S) classification. We furthermore discuss new issues which might be considered for future updates of the MOGE(S) classification of cardiomyopathies.

Objective To assess risk factors for paravalvular leak (PVL) after transcatheter aortic valve implantation in a large single-center cohort, including measurement of aortic valve calcification using a reproducible method. Methods We retrospectively analyzed preoperative contrast-enhanced multidetector computed tomography scans of patients who underwent transcatheter aortic valve implantation in our center between 2009 and 2016. Calcium volume was calculated for each aortic cusp in the aortic valve, left ventricular outflow tract, and device landing zone. Results Overall, 539 patients were included in the study who had experience with 4 prothesis types (SapienXT [Edwards Lifesciences, Irvine, Calif] [n = 192], Sapien3 [Edwards Lifesciences] [n = 206], CoreValve EvolutR [Medtronic, Minneapolis, Minn] [n = 44], and Acurate [Symetis, Ecublens, Switzerland] [n = 97]). Median calcium volume in the device landing zone was 757 mm3, with no significant differences among the 4 prosthesis groups. None of the patients had severe PVL. The overall incidence of mild-to-moderate PVL was 15.8% (95% confidence interval [CI], 12.8%-19.1%). On multivariate logistic regression, device landing zone calcification (P = .00006; odds ratio for an increase of 100 mm3, 1.08; 95% CI, 1.04-1.13) and use of the CoreValve (P = .0028; odds ratio, 4.1; 95% CI, 1.6-10 with SapienXT as reference) prosthesis were found to be associated with mild or greater PVL. In contrast, degree of oversizing (P = .002; odds ratio, 0.97; 95% CI, 0.95-0.99), and use of Sapien3 (P = .00005; odds ratio, 0.23; 95% CI, 0.11-0.47 with SapienXT as reference) were associated with a lower incidence of mild or greater PVL. Conclusions Aortic calcification volume in the device landing zone is associated with residual PVL after transcatheter aortic valve implantation. When taking calcification into account, the balloon-expandable prosthesis Sapien3 seems to be associated with a lower incidence of PVL.

Background— The prognostic significance of papillary muscle infarction (PapMI) on hard clinical outcomes has not been investigated in patients with reperfused ST-segment–elevation myocardial infarction. Noninvasive investigation by gadolinium-enhanced cardiac MRI enables the detection of PapMI with high spatial resolution. The aim of our study was (1) to assess the incidence, determinants, and clinical characteristics of PapMI in a large multicenter cohort of patients with ST-segment–elevation myocardial infarction and (2) to assess the prognostic significance of PapMI at 1-year follow-up. Methods and Results— We enrolled 738 patients with ST-segment–elevation myocardial infarction reperfused by primary angioplasty (P P P P =0.02). Patients with PapMI had a significantly higher mortality (8 [7.7%] versus 12 [1.9%]) and major adverse cardiac events (21 [20.2%] versus 31 [4.9%]) rate at 12-month follow-up ( P P Conclusions— The presence of PapMI is associated with decreased myocardial salvage, larger infarcts, and more pronounced reperfusion injury with subsequent significantly increased major adverse cardiac event rates. Consequently, our data underscore the importance of PapMI as a marker of poor outcome in patients with ST-segment–elevation myocardial infarction. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00712101.

Objectives The aim of the AIDA STEMI (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction) cardiac magnetic resonance (CMR) substudy was to investigate potential benefits of intracoronary versus intravenous abciximab bolus administration on infarct size and reperfusion injury in ST-segment elevation myocardial infarction. Background The AIDA STEMI trial randomized 2,065 patients to intracoronary or intravenous abciximab and found similar rates of major adverse cardiac events at 90 days with significantly less congestive heart failure in the intracoronary abciximab group. CMR can directly visualize myocardial damage and reperfusion injury, thereby providing mechanistic and pathophysiological insights. Methods We enrolled 795 patients in the AIDA STEMI CMR substudy. CMR was completed within 1 week after ST-segment elevation myocardial infarction. Central core laboratory–masked analyses for quantified ventricular function, volumes, infarct size, microvascular obstruction, hemorrhage, and myocardial salvage were performed. Results The area at risk (p = 0.97) and final infarct size (16% [interquartile range: 9% to 25%] versus 17% [interquartile range: 8% to 25%], p = 0.52) did not differ significantly between the intracoronary and the intravenous abciximab groups. Consequently, the myocardial salvage index was similar (52 [interquartile range: 35 to 69] versus 50 [interquartile range: 29 to 69], p = 0.25). There were also no differences in microvascular obstruction (p = 0.19), intramyocardial hemorrhage (p = 0.19), or ejection fraction (p = 0.95) between both treatment groups. Patients in whom major adverse cardiac events occurred had significantly larger infarcts, less myocardial salvage, and more pronounced ventricular dysfunction. Conclusions This largest multicenter CMR study in ST-segment elevation myocardial infarction patients to date demonstrates no benefit of intracoronary versus intravenous abciximab administration on myocardial damage and/or reperfusion injury. Infarct size determined by CMR was significantly associated with major adverse cardiac events. (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction [AIDA STEMI]; NCT00712101 )

Recently, a new device for noninvasive assessment of central systolic blood pressure (cSBP) (BPro device with A-Pulse) was approved by the US Food and Drug Administration, but available data are limited. In 52 patients undergoing invasive elective cardiac evaluation, central hemodynamics were measured invasively. Immediately thereafter, radial artery waveforms were sampled by two noninvasive techniques, the BPro and, as a comparator, the SphygmoCor System. Then, central hemodynamics were measured invasively for a second time. The invasively recorded cSBP (137 ± 27 mm Hg) did not differ with both noninvasively assessed cSBP by BPro (136 ± 21 mm Hg, P = .627 vs invasive cSBP) and by SphygmoCor (136 ± 23 mm Hg, P=.694 vs invasive cSBP) and correlated highly between invasively recorded and both noninvasively assessed cSBP. However, using Bland-Altman plots, spreading of compared data of both devices can be found (BPro: 0.87 ± 13 mm Hg vs invasive cSBP; SphygmoCor: 0.77 ± 14 mm Hg vs invasive cSBP). There was an excellent correlation of both noninvasive devices for the calculation of cSBP (r=0.961, P

Left ventricular hypertrophy can be a sequel of numerous clinical entities. Decisive for the diagnosis is the delineation of primary myocardial hypertrophy from secondary forms of hypertrophy since this has far-reaching consequences for the prognosis of and therapy for the individual diseases. Hypertrophic cardiomyopathy in particular requires an especially careful diagnosis with regard to the prevention of sudden cardiac death, above all because mainly younger patient collectives are concerned. Besides the case history, ausculation, electrocardiograhy and 2D echo cardiography, further procedures such as tissue Doppler echo cardiography, endomyocardial biopsy as well as contrast-enhanced cardiavascular MRI are indispensable elements in the differential diagnosis of left ventricular hypertrophy.

Left ventricular (LV) remodeling is known to contribute to morbidity and mortality after myocardial infarction (MI). Because LV remodeling is strongly associated with an inflammatory response, we investigated whether or not TLR-4 influences LV remodeling and survival in a mice model of MI. Six days after MI induction, TLR4 knockout (KO)-MI mice showed improved LV function 32 and reduced LV remodeling as indexed by reduced levels of atrial natriuretic factor and total collagen as well as by a reduced heart weight to body weight ratio when compared with WT-MI mice. This was associated with a reduction of protein levels of the intracellular TLR4 adapter protein MyD88 and enhanced protein expression of the anti-hypertrophic JNK in KO-MI mice when compared with wild-type (WT)-MI mice. In contrast, protein activation of the pro-hypertrophic kinases protein kinase Cδ and p42/44 were not regulated in KO-MI mice when compared with WT-MI mice. Improved LV function, reduced cardiac remodeling, and suppressed intracellular TLR4 signaling in KO-MI mice were associated with significantly improved survival compared with WT-MI mice (62 vs 23%; p < 0.0001). TLR4 deficiency led to improved survival after MI mediated by attenuated left ventricular remodeling.

Background— Increased left ventricular stiffness is a distinct finding in patients who have heart failure with normal ejection fraction (HFNEF). To elucidate how diastolic dysfunction contributes to heart failure symptomatology during exercise, we conducted a study using an invasive pressure-volume loop approach and measured cardiac function at rest and during atrial pacing and handgrip exercise. Methods and Results— Patients with HFNEF (n=70) and patients without heart failure symptoms (n=20) were enrolled. Pressure-volume loops were measured with a conductance catheter during basal conditions, handgrip exercise, and atrial pacing with 120 bpm to analyze diastolic and systolic left ventricular function. During transient preload reduction, the diastolic stiffness constant was measured directly. Diastolic function with increased stiffness was significantly impaired in patients with HFNEF during basal conditions. This was associated with increased end-diastolic pressures during handgrip exercise and with decreased stroke volume and a leftward shift of pressure-volume loops during atrial pacing. Conclusions— Increased left ventricular stiffness contributed to increased end-diastolic pressure during handgrip exercise and decreased stroke volume during atrial pacing in patients with HFNEF. These data suggest that left ventricular stiffness modulates cardiac function in HFNEF patients and suggests that diastolic dysfunction with increased stiffness is a target for treating HFNEF.

HISTORY AND CLINICAL FINDINGS Two days before admission a 22-year-old woman developed general fatigue, nausea, headache and retrosternal pain. Physical examination was unremarkable. INVESTIGATIONS Erythrocyte sedimentation rate was increased to 20/48, C-reactive protein to 3.3 mg/dl, and there was evidence of myocardial damage (creatine kinase 609 U/l, creatine kinase-MB 42 U/l, troponine T 8.39 ng/ml); ST-segment elevations in I, II, III, aVF and V-V6 of the ECG. Echocardiography revealed clearly thickened myocardium, moderate but haemodynamically not significant pericardial effusion, as well as impaired left ventricular function. Antimyosin scintigraphy was very abnormal. Cardiac catheterization confirmed the left ventricular dysfunction, rise of left ventricular enddiastolic pressure to 17 mm Hg, and a markedly reduced cardiac output of 2.4 l/min. Myocardial biopsy showed severe myocarditis with marked myocytolysis and considerable lymphocytic infiltrations. Enteroviral RNA was demonstrated in the myocardium by polymerase chain reaction. TREATMENT AND COURSE The haemodynamics became normal within only 3 days. Myocardial biopsy after 6 months was unremarkable histologically and immunohistologically, and left ventricular function was also normal. However, while after a further 12 months myocardial biopsy remained normal and no virus was demonstrated, there was definite, though moderate, impairment in left ventricular function, indicating a dilated cardiomyopathy. INTERPRETATION Even when histological and immunohistological evidence of healing of an acute viral myocarditis has been achieved, with complete normalization of left ventricular function, a dilated cardiomyopathy may subsequently develop. The pathophysiological mechanism of this occurrence remains unknown.

History and clinical findings A 28-year-old woman was admitted after syncope which had been preceded by several flulike episodes. There was no history of any other serious disease. Physical examination was unremarkable. Heart sounds were regular and normal, there were no murmurs. Investigations White cell count was 9400/microliter, with a normal differential count. Erythrocyte sedimentation rate and C-reactive protein were also normal. Virus serology revealed no abnormality. The electrocardiogram (ECG) showed complete (third degree) atrioventricular (AV) block with an idioventricular rhythm of 38 beats/min and right bundle branch block pattern. Treatment and course A temporary transvenous pacemaker was inserted on the first hospital day. As myocarditis was suspected a right ventricular endomyocardial biopsy was obtained. Histological and immunohistological examinations demonstrated no unequivocal findings. But molecular-biological tests revealed. Coxsackie-B3 virus genome. The pacemaker was removed on the 6th day, when the ECG had shown intermittent second degree AV block. Regular sinus rhythm with a PR interval of 0.18 s was recorded on day 12, and 24-hour ECG monitoring for several days until her discharge on the 18th day confirmed this rhythm throughout. Conclusion In aetiologically undetermined disease molecular-biological techniques can be indispensable for the exact diagnosis and may be decisive for administering specific treatment.

Prof. Dr. Andre Keren ()) Center for Heart Failure and Heart Muscle Diseases Heart Institute Hadassah University Hospital Hadassah-Hebrew University Medical School Jerusalem 91120, Israel E-Mail: andrek@cc.huji.ac.il Hypertrophic cardiomyopathy (HCM), defined clinically by the presence of unexplained left ventricular hypertrophy [1], is the most common inherited cardiac disorder affecting one in 500 people [2, 3]. Approximately 25% of patients have left ventricular outflow obstruction at rest and 70% can develop outflow gradients during exercise [4]. The dynamic outflow obstruction is caused by the abnormal systolic contact between the hypertrophied basal interventricular septum and the anterior mitral leaflet

Cardiac autoantibodies play a pathogenic role in dilated cardiomyopathy (DCM). Removal of antibodies by immunoadsorption (IA) induces hemodynamic improvement in DCM patients. The present study investigated the effects of IA on myocardial gene expression of the intermediate cytoskeletal filament desmin, which is upregulated in heart failure. RNA was isolated from five explanted non-failing hearts and five explanted failing hearts of DCM patients, and myocardial gene expression of desmin was estimated by real-time polymerase chain reaction (PCR). In a case-control study in six DCM patients (LVEF

Background— Various conventional and tissue Doppler echocardiographic indexes were compared with pressure–volume loop analysis to assess their accuracy in detecting left ventricular (LV) diastolic dysfunction in patients with heart failure with normal ejection fraction (HFNEF). Methods and Results— Diastolic dysfunction was confirmed by pressure–volume loop analysis obtained by conductance catheter in 43 patients (19 men) with HFNEF. Their Doppler indexes were compared with those of 12 control patients without heart failure symptoms and with normal ejection fraction. Invasively measured indexes for diastolic relaxation (τ, dP/dt min ), LV end-diastolic pressure, and LV end-diastolic pressure–volume relationship (stiffness, b [dP/dV], and stiffness constant, β) were correlated with several conventional mitral flow and tissue Doppler imaging indexes. Conventional Doppler indexes correlated moderately with the degree of LV relaxation index, τ (E/A: r =−0.36, P =0.013; isovolumic relaxation time: r =0.31, P =0.040) and b (deceleration time: r =0.39, P =0.012) but not with β, in contrast to the tissue Doppler imaging indexes E’/A’ lateral ( r =−0.37, P =0.008) and E/E’ lateral ( r =0.53, P lateral , and E/E’ lateral , respectively. Conclusions— Of all echocardiographic parameters investigated, the LV filling index E/E’ lateral was identified as the best index to detect diastolic dysfunction in HFNEF in which the diagnosis of diastolic dysfunction was confirmed by conductance catheter analysis. We recommend its use as an essential tool for noninvasive diagnostics of diastolic function in patients with HFNEF.

Objective Despite the success of antiproliferative therapies, restenosis remains a common problem after percutaneous transluminal coronary angioplasty (PTCA). Longer-term clinical results of brachytherapy (intracoronary radiation), the lack of long-term clinical results after implantation of drug eluting stents, and the occurrence of late thrombosis after both procedures leave room for skepticism. Neointimal proliferation is not substantially inhibited at late time points after brachytherapy, and late lumen loss with a “catch-up” proliferation can occur. We hypothesized that the transcription factors nuclear factor-{kappa}B (NF-κB) and activator protein-1 (AP-1) are involved in these processes. We addressed the role of these mediators in a porcine model of coronary restenosis. Methods Thirty-nine pigs underwent PTCA in two major coronary arteries. One of the two balloon-injured arteries was randomly assigned to receive immediate 20 Gy beta-irradiation (Brachy group) using a noncentered source train (90Sr/Y Beta-Cath, Novoste). Animals were sacrificed after 1 day, 14 days, or 28 days. Proliferating cells were labeled prior to euthanasia. Results At late time points, lumen area was significantly smaller and the inflammatory response was more pronounced in the Brachy group than in the PTCA group. These findings coincided with sustained activation of MMP-9 and transcription factors like NF-κB and AP-1. Initially, cell proliferation was reduced in the Brachy group; however, at late time points, differences between the two treatment groups were no longer significant. Conclusions Brachytherapy initially inhibits cell proliferation; however, cellular and molecular inflammatory processes (e.g. activation of NF−κB) are enhanced within the arterial wall. This proinflammatory side effect may be responsible for the observed delayed proliferation and the resulting lumen loss.

Intravenous inotropic therapy may be necessary to achieve short-term survival in end-stage heart failure patients with cardiogenic shock or extreme low output and severe organ hypoperfusion. However, mid- or long-term intravenous inotropic therapy is associated with an increased mortality in advanced stage D heart failure patients using β-adrenoceptor agonists (dobutamine) or PDE-3-inhibitors (milrinone). Intermittent levosimendan may evolve as a reasonable therapeutic option. Randomized trials or other meaningful scientific evidence addressing the optimal treatment of exclusively the most threatened subgroup of hospitalized patients with persistent severe organ hypoperfusion are missing, but urgently needed. Despite a lack of other beneficial pharmacological options, the use of long-term intravenous inotropic therapy as a treatment for refractory heart failure or as an obligatory criterion for high urgency (HU) listing of heart transplant candidates with a median waiting time of 66 days in Germany is not based on scientific evidence. In addition, it might create a disincentive to achieve the HU status as well as keeping it, thereby potentially exposing the patient to an unnecessary additional risk. Upcoming new allocation algorithms may possibly help to improve the inadequate present situation. There is need for both, a better definition and a better treatment of high risk terminal heart failure requiring high urgent transplant listing.

Surgical sutureless and interventional transcatheter aortic valve prostheses are nowadays extensively adopted in high-risk elderly patients. An explorative analysis was carried out to compare the clinical outcome and costs associated to these approaches. Since 2010, a total of 626 patients were distributed between transcatheter aortic valve implantation (TAVI; n = 364) and sutureless (n = 262) groups. Patients of both groups were not comparable for clinical and surgical characteristics, but many patients were in a "gray zone"; therefore, a retrospective propensity score analysis was possible and performed. For the matched pair samples, postoperative, follow-up clinical data, and costs data were obtained. In-hospital death occurred in 5 patients in sutureless group and 3 patients in TAVI group (p = 0.36). Blood transfusions were higher in sutureless group (2.1 ± 2.3 vs 0.4 ± 1.0 U). TAVI group had a shorter intensive care unit and hospital stay (2.2 ± 2.7 vs 3.2 ± 3.5 days, p = 0.037; 12 ± 6 vs 14 ± 6 days, p = 0.017). No differences in postoperative neurologic (p = 0.361), renal (p = 0.106), or respiratory (p = 0.391) complications were observed between groups. At follow-up (24.5 ± 13.8 months), 1 patient in sutureless group and 7 patients in TAVI group died (p = 0.032). Paravalvular leakage occurred more frequently in patients in TAVI group (35 [34%] vs 7 [6.9%]; p

This review focuses on hypertrophic (HCM), restrictive (RCM) and arrhythmogenic right ventricular cardiomyopathies (ARVC). The clinical phenotype of HCM depends not only on the gene mutations involved, but also on "modifier genes". It is characterized by an asymmetrical hypertrophy. Investigations of endomyocardial biopsies (EMBs) typically reveal a disarray of the hypertrophied cardiomyocytes. Percutaneous septum ablation has gained relevance as the treatment of choice in hypertrophic obstructive cardiomyopathy. Myocardial and endomyocardial RCM-forms can be differentiated. Enlargement of the atria in concert with normal dimensions of the ventricles and almost normal systolic contractility as well as the dip-plateau phenomenon are characteristic findings in RCM. EMB diagnostics are pivotal to identify the causes underlying secondary RCM types. Treatment is directed at heart failure and specifically at the underlying disease. With ARVC, apoptosis, viral infection/inflammation and genetic dystrophy result in fibrofatty degeneration primarily of the right, and with further progression also of the left ventricle. The primary treatment goal in ARVC is prevention of sudden cardiac death. As for other cardiomyopathies, there is increasing evidence for the superiority of ICD compared with pharmacological approaches.

Cardiomyopathies are common causes of heart failure and sudden cardiac death. According to the WHO classification, "specific" cardiomyopathies are differentiated from "idiopathic" cardiomyopathies. Thus, this classification is primarily based on pathophysiological characteristics. The diagnostic spectrum in cardiomyopathies comprises the entire spectrum of non-invasive and invasive cardiological examination techniques. The exact verification of certain cardiomyopathies necessitates additionally investigations. For example, immunohistological and molecular biological investigations of endomyocardial biopsies may confirm inflammatory cardiomyopathy, which is often induced by viruses. Several studies have shown that specific immunomodulatory treatment options can halt the progressive course of the disease. Several gene mutations have been identified in genetic/familial dilated cardiomyopathy. First-degree relatives should be screened for early stages. Primary prevention of sudden cardiac death shows increasing superiority of the implantable defibrillator compared with pharmacological approaches (i.e. amiodarone).

Background : Carvedilol, a vasodilating nonselective β-adrenoceptor antagonist, but not metoprolol, a selective β 1 -adrenoceptor antagonist, has been shown to increase the production of cardiac antiinflammatory cytokines in experimental myocarditis. However, the hemodynamic consequences of these differences had not been investigated until today. Therefore, we determined the effects of carvedilol and metoprolol on left ventricular function in a murine model of coxsackievirus B3 (CVB3)-induced myocarditis. Methods : BALB/c mice were inoculated with the coxsackie-B3 virus. Four and 10 days after infection, left ventricular function was investigated using a conductance micromanometer system. Additional groups were treated starting 24 h after infection using equipotent doses of carvedilol and metoprolol and studied on day 10. Results : On day 4, infected mice manifested increased afterload-enhanced contractility and abnormal diastolic function. On day 10, contractile function of untreated mice was impaired. Carvedilol significantly improved cardiac index and most systolic indices, whereas metoprolol was substantially less effective. Diastolic dysfunction was not influenced by either of the β-adrenoceptor antagonists. Conclusions : These hemodynamic data indicate that not only β 1 -adrenoceptor blockade but also pleiotropic effects are involved in the cardioprotective effects of carvedilol on the pathophysiology of acute viral myocarditis.

Background— Viral infections are important causes of myocarditis and may induce cardiac dysfunction and finally lead to dilated cardiomyopathy. We investigated whether interferon (IFN)-β therapy is safe and may achieve virus clearance and prevent deterioration of left ventricular (LV) function in patients with myocardial virus persistence. Methods and Results— In this phase II study, 22 consecutive patients with persistence of LV dysfunction (history of symptoms, 44±27 months) and polymerase chain reaction–proven enteroviral or adenoviral genomes were treated with 18×10 6 IU/week IFN-β (Beneferon) subcutaneously for 24 weeks. Histological and immunohistological analysis of endomyocardial biopsies was used to characterize myocardial inflammation. LV diameters and ejection fraction were assessed by echocardiography and angiography, respectively. During the treatment period, IFN-β was well tolerated by all patients. No patient deteriorated. Clearance of viral genomes was observed in 22 of 22 of patients after antiviral therapy. Virus clearance was paralleled by a significant decrease of LV end diastolic and end systolic diameters, decreasing from 59.7±11.1 to 56.5±10.0 mm ( P P P Conclusions— A 6 months, IFN-β treatment was safe in patients with myocardial enteroviral or adenoviral persistence and LV dysfunction and resulted in elimination of viral genomes (22 of 22 patients) and improved LV function (15 of 22 patients).

Nonrandomized studies suggested lower mortality rates with statin pretreatment in patients with acute ST elevation myocardial infarction (STEMI). However, clinical data are still inconclusive and the mechanisms of these presumed beneficial effects require further exploration. Cardiac magnetic resonance (CMR) imaging offers the possibility of studying a variety of markers of myocardial damage and reperfusion injury after myocardial infarction. The aim of this study was to assess a possible link of statin pretreatment with myocardial damage in acute STEMI. The multicenter Abciximab i.v. versus i.c. in ST-elevation Myocardial Infarction CMR substudy enrolled 795 consecutive patients with acute STEMI who underwent primary angioplasty within 12 hours of symptom onset. CMR studies assessing left ventricular ejection fraction, infarct size, microvascular obstruction, area at risk, and myocardial salvage index were performed in a median of 3 days after the clinical event. We performed a retrospective analysis to evaluate the impact of statin pretreatment on myocardial damage. Information on statin pretreatment was available in 791 of 795 patients (99%). Of these, 122 (15%) had long-term statin pretreatment. CMR results showed no significant differences in the area at risk, left ventricular ejection fraction, infarct size, microvascular obstruction, and myocardial salvage index between patients with and without statin pretreatment. Furthermore, no differences in short- and long-term outcomes could be observed. In conclusion, in this CMR study, statin pretreatment in patients with STEMI was not associated with lesser myocardial damage.

Limited data exist regarding baseline characteristics and management of heart failure with reduced ejection fraction (EF) in tertiary care facilities. EVITA-HF comprises web-based case report data on demography, comorbidities, diagnostic and therapy measures, quality of life, adverse events and 1-year follow-up of patients hospitalized for chronic heart failure and an ejection fraction of less than 40 %. Between February 2009 and June 2011, a total of 1,853 consecutive, hospitalized patients (pts) were included in 16 centers in Germany. Mean age was 70 years, 76 % were male. Median EF was 30 %, and 63 % were in NYHA III/IV. Ischemic cardiomyopathy was present in 56 %, history of hypertension in 76 %, diabetes in 39 %, impaired renal function in 33 %, thyroid dysfunction in 12 %, and malignoma in 7 %. Sixty-eight percent of pts had a non-elective admission. Rhythm was sinus/atrial fibrillation or flutter/pacemaker in 64, 28 and 11 %, respectively. Median heart rate amounted to 80 bpm, median blood pressure to 122/74 mmHg. LBBB was present in 26 % of non-pacemaker pts. Eighteen percent had an ICD or CRT-D. Medication (admission vs. discharge) consisted of ACEI or ARB in 73 vs. 88 %, β-blocker in 71 vs. 89 %, mineral corticosteroid receptor antagonist (MRA) in 32 vs. 57 %, diuretics in 68 vs. 83 % (p

Objectives. The present study investigated whether myocyte injury can be assessed sensitively by measurement of serum levels of cardiac troponin T (cTnT) in patients with clinically suspected myocarditis and whether cTnT levels may predict the results of histologic and immunohistologic analysis of endomyocardial biopsy specimens. Background. Conventionally used laboratory variables often fail to show myocyte injury in patients with clinically suspected myocarditis, possibly because of a low extent of myocardial injury in these patients. Sensitive variables for myocyte injury have not yet been investigated. Methods. Eighty patients with clinically suspected myocarditis were screened for creatine kinase (CK) activity, MB isoform of CK (CK-MB) activity and cTnT. Endomyocardial biopsy specimens were examined histologically and immunohistologically. Results. cTnT was elevated in 28 of 80 patients with clinically suspected myocarditis, CK in 4 and CK-MB in 1. Histologic analysis alone of the endomyocardial biopsy specimen revealed evidence of myocarditis in only five patients, all with elevated cTnT levels. Twenty-three of 28 patients with elevated cTnT levels had histologically negative findings for myocarditis. Additional immunohistologic analysis revealed evidence of myocarditis in 26 (93%) of 28 patients with elevated cTnT levels and in 23 (44%) of 52 patients with normal cTnT levels. Mean cTnT levels were higher in patients with myocarditis proved histologically or immunohistologically, or both, than in patients without myocarditis (0.59 ± 1.68 vs. 0.04 ± 0.05, p < 0.001). Conclusions. Measurement of serum levels of cTnT provides evidence of myocyte injury in patients with clinically suspected myocarditis more sensitively than does conventional determination of cardiac enzyme levels. Myocardial cell damage may be present even in the absence of histologic signs of myocarditis. Additional immunohistologic analysis often shows lymphocytic infiltrates in these patients. Elevated levels of cTnT are highly predictive for myocarditis in this group.

Data on the impact on clinical outcome of cardiac magnetic resonance imaging (CMR) parameters in patients with ST-elevation myocardial infarction (STEMI) are limited due to analysis of single-center cohorts and small study sample sizes. Aim of the current study was to investigate the prognostic

The need for implantable cardioverter-defibrillator (ICD) defibrillation testing (DT) and subsequent intraoperative system modifications is discussed controversially. The study’s goal was to prove that consequent abdication of intraoperative DT does not impair defibrillation efficacy and does not increase the rate of postoperative system revisions. In a prospective single-center observational study, 609 out of 648 consecutive patients underwent transvenous ICD implantation (left-sided, active can, dual coil lead, and biphasic shock waveform) waiving intraoperative DT. Defibrillation efficacy was validated prior to hospital discharge (PHD) by applying two 10 J safety margin (SM) shocks. Following “schockless” implantation 580 out of 609 patients (95.2 %) met a 10 J SM with default programming. Shock path reversal provided 10 J SM in 13 out of 29 cases with initially failed DT. In four patients (0.7 %) maximum energy shocks were ineffective. There was no morbidity or mortality related to DT. The total rate of surgical ICD revisions was 1.8 %. Routine ICD implantation without intraoperative DT does not lead to an increased rate of postoperative system modifications and does not decrease defibrillation efficacy as tested PHD.

Inflammatory cardiomyopathy (DCMi) is commonly induced and maintained by cardiotropic viruses, and is associated with left ventricular (LV) dysfunction accompanied by myocardial inflammatory cell infiltration and increased release of proinflammatory cytokines. Recent insights have revealed the pivotal role played by the disruption of the extracellular matrix (ECM) architecture, caused mainly by cytokine-driven post-translational modification. Fibrillar collagen turnover results from the equilibrium between synthesis and degradation. The imbalance of the matrix degrading system with induced expression of metalloproteinases (MMPs) and plasminogen activators, and with concomitantly reduced expression of the tissue inhibitors of MMPs, contributes to a pathological collagen turnover. This results in a loss of myocardial structural integrity and impairment of LV function. Interference with ECM regulatory mechanisms may be effective in preventing persistent virus-induced and cytokine-driven cardiac injury. Future investigations are warranted to elucidate the possible effects of established immunomodulatory treatment strategies on the expression, biological activity and architecture of ECM components.

We would like to thank Dr Kass for his interest in our study, which investigated hemodynamic characteristics of patients with heart failure and normal ejection fraction (HFNEF).1 An important finding in our study was that with increased paced heart rates the patients in the HFNEF group showed a decrease in end-diastolic volume leading to reduced stroke volume, which limited their ability to increase cardiac output and may explain their exertional limitations. These results were in contrast to those in the control group where end-diastolic volumes and stroke …

To investigate the potential benefit of an earliest possible out-of-hospital start of abciximab (ReoPro) therapy in ST-elevation myocardial infarction (STEMI; Lilly, Bad Homburg, Germany) and planned primary percutaneous intervention compared with periprocedural abciximab treatment on reperfusion and clinical outcome.Randomization of one hundred and one patients with STEMI to prehospital or periprocedural abciximab treatment. Evaluation of thrombolysis in myocardial infarction (TIMI) flow, ST-segment resolution, myocardial blush grade, and maximal creatine kinase release before and after as well as clinical follow-up until 6 months after the index event.Prehospital abciximab (group 1) was initiated a median of 101 min (37-165 min) earlier compared with periprocedural treatment (group 2). Initial TIMI 3 flow (24 vs. 15%, P=NS), ST-segment resolution before percutaneous coronary intervention (PCI) (30%: 33 vs. 46%, P=NS;70%: 38 vs. 33%, P=NS), post-PCI myocardial blush grade 2 and 3 (72 vs. 75%, P=NS), maximal cardiac enzyme release (creatinine kinase MB median 77 U/l; range 33-137 vs. 74 U/l; range 39-143 U/l, P=NS), and 6 months follow-up (recurrent myocardial infarction or repeat coronary intervention, and PCI, need for coronary bypass surgery) did not differ significantly between both treatment groups.Prehospital intravenous administration of abciximab, although safe and feasible in a trained surrounding, does not add angiographic or clinical benefit to patients with STEMI.

Background The short-term results for the prevention of coronary restenosis after intravascular brachytherapy (IVBT) and use of drug-eluting stents (DESs) are excellent. The long-term results either lack or present with late complications (e.g., late thrombosis and late catch-up phenomenon leading to late restenosis even years after the initial procedure). Both IVBT and DESs mediate their potent antirestenotic effects via a cytostatic mechanism, but the cardiovascular pathology at late time points after the use of these antiproliferative therapies is incompletely understood. This study investigated the long-term effects of antiproliferative beta-irradiation in a clinically relevant porcine coronary model to address the pathophysiology of late coronary restenosis after antiproliferative vascular interventions. Methods We performed percutaneous transluminal coronary angioplasty (PTCA) in two major coronary arteries in 12 domestic crossbred pigs. One of the two balloon-injured segments was randomly assigned to receive immediate beta-irradiation (PTCA+IVBT group) using a noncentered delivery catheter (20 Gy; Novoste Beta-Cath System, Novoste, Norcross, GA, USA). The animals were sacrificed after 14 days ( n =6) or 3 months ( n =6). Results The luminal area in the PTCA+IVBT group decreased significantly 3 months after the intervention as compared with that in the PTCA group (PTCA 3.45±0.46 mm 2 vs. PTCA+IVBT 1.22±0.26 mm 2 ; P =.0017). This lumen loss was primarily due to shrinkage of the external elastic lamina area (negative arterial remodeling; PTCA 5.22±0.27 mm 2 vs. PTCA+IVBT 3.42±0.45 mm 2 ; P =.0064), which was accompanied by an increase in the adventitial area (PTCA 3.07±0.2 mm 2 vs. PTCA+IVBT 5.41±0.5 mm 2 ; P =.0049). Conclusions The application of antiproliferative radiation in a porcine coronary model caused an early beneficial effect (reduction of intimal–medial lesion and luminal gain) that was followed by a late lumen loss primarily due to negative arterial remodeling. This mechanism may in part help us understand the pathophysiology of late adverse events occurring after IVBT.

A previously healthy 39-year-old man was admitted to our department with biventricular cardiac decompensation (New York Heart Association class IV) and acute onset of angina pectoris after a flulike disease 1 week earlier. The ECG on admission displayed ST elevations in II, III, and aVF. Troponin T on admission was increased (2.20 mg/L, normal value

Recently, it has been demonstrated that myocardial inflammation plays a pivotal role in the development and progression of congestive heart failure. The myocardial inflammatory reaction not only affects myocardial hypertrophy and apoptosis, but it has a major influence on the regulation of extracellular matrix turnover. The balance between collagen synthesis and degradation is of crucial relevance in maintaining the structural integrity of the heart. Therefore, the overwhelming inflammatory response, as seen in acute myocarditis or inflammatory cardiomyopathy, could lead to a breakdown of this tightly regulated system. This is an additional key factor in the development and progression of heart failure. This review summarizes the importance of myocardial inflammation in respect to extracellular matrix remodeling and its possible patho-physiological role in the development and progression of left ventricular dysfunction in inflammatory heart disease.

Background: The cardiac troponin T I79N mutation, linked to familial hypertrophic cardiomyopathy, carries a high risk of sudden cardiac death even in the absence of significant cardiac hypertrophy. The pathology underlying this mechanism has not yet been identified. Aims: To study the underlying mechanism of this phenomenon we characterized the left ventricular (LV) performance of transgenic mice carrying the human troponin T mutation I79N under basal and isoproterenol-induced stress conditions. Methods and results: LV function was analyzed by recording pressure—volume loops using a microconductance catheter. Despite a hypercontractile systolic function under basal conditions TnT-I79N mice showed a diastolic dysfunction indicated by an increase in end-diastolic pressure—volume relationship (EDPVR), a load-independent factor of LV stiffness (0.06±0.01 vs. 0.02±0.01; P

To the Editor: In patients with ST-segment elevation myocardial infarction (STEMI), direct intracoronary as compared with standard intravenous bolus administration of the glycoprotein IIb/IIIa receptor antagonist abciximab acutely causes higher local drug concentrations, greater glycoprotein IIb/

Background— Enteroviruses (EVs) and adenoviruses (ADVs) have been considered common causes of myocarditis and dilated cardiomyopathy. In the present study, we report on the association of parvovirus B19 (PVB19) genomes in the clinical setting of acute myocarditis. Methods and Results— This study included 24 consecutive patients admitted to our hospital within 24 hours after onset of chest pain. Acute myocardial infarction had been excluded in all patients by coronary angiography. Endomyocardial biopsies were analyzed by nested polymerase chain reaction/reverse transcriptase-polymerase chain reaction for EV, ADV, PVB19, human cytomegalovirus, Epstein-Barr virus, Chlamydia pneumoniae , influenza virus A and B, and Borrelia burgdorferi genomes, respectively, followed by direct sequencing of the amplification products. All patients presented with acute onset of angina pectoris and ST-segment elevations or T-wave inversion mimicking acute myocardial infarction. Mean baseline peak creatinine kinase and creatine kinase-isoenzyme fraction were 342±241 U/L and 32±20 U/L, respectively. Mean troponin T was increased to 7.5±15.0 ng/mL and C-reactive protein to 91±98 mg/mL. Eighteen patients had global or regional wall motion abnormalities (ejection fraction 62.5±15.5%). Histological analysis excluded the presence of active or borderline myocarditis in all but one patient. PVB19, EV, and ADV genomes were detected in the myocardium of 12, 3, and 2 patients, respectively (71%). Follow-up biopsies of virus-positive patients (11 of 17) demonstrated persistence of PVB19 genomes in 6 of 6 patients, EV genomes in 2 of 3 patients, and ADV genomes in 1 of 2 patients, respectively. Conclusions— Virus genomes can be demonstrated in 71% of patients with normal coronary anatomy, clinically mimicking acute myocardial infarction. In addition to EVs and ADVs, PVB19 was the most frequent pathogen.

Background Data on the prognostic value of cardiac magnetic resonance imaging (CMR) parameters in patients with STelevation myocardial infarction (STEMI) are limited due to analysis of single-center cohorts and small study sample sizes. Aim of the current study was thus to investigate the impact of infarct size, microvascular obstruction (MO) and myocardial salvage index (MSI) on clinical outcome in a large cohort of STEMI patients derived from a multi-center study. Methods STEMI patients (n=795) reperfused by primary percutaneous coronary intervention (PCI) within 12 hours after symptom onset underwent CMR in 8 centers in Germany. CMR was performed at day 1 to 4 after the index event. Infarct size and microvascular obstruction (MO) were measured 15 minutes after gadolinium injection. T2-weighted and contrast-enhanced CMR were used to calculate the MSI. The primary endpoint was defined as a composite of death, non-fatal myocardial reinfarction and congestive heart failure (MACE). Clinical follow-up was conducted after 12 months. Results Infarct size, MO and MSI were significantly associated with MACE in univariable Cox regression analysis (all p