Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry.

BACKGROUND AND AIMS: Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS: Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS: Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS: Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.

Diagnosis and treatment of cardiac amyloidosis. A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases.

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.

Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases.

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.

Measuring Anxiety in Older Adults: Development, Diagnostic Accuracy, and Preliminary Validation of a Short-Form of the German Geriatric Anxiety Scale (GAS-G-SF).

Anxiety symptoms and anxiety disorders are highly prevalent among older adults, and are associated with considerable distress, functional impairment, and burden. Also, there is growing need for brief instruments to measure anxiety symptoms in primary care and geriatric medical settings. Therefore, the current study focuses on the development and psychometric evaluation of a short-form of the Geriatric Anxiety Scale (GAS-G), a well-established anxiety instrument for use with older adults. Study 1 draws on the original data from the GAS-G validation study (N = 242) to develop the short-form (GAS-G-SF) and determines whether the results replicate with the short-form. Study 2 extends the validation of the GAS-G-SF to a clinical sample (N = 156; 62 patients with heart disease, 94 patients with Parkinson's disease). Overall, the GAS-G-SF showed promising psychometric properties in terms of internal consistency and validity. Also, the GAS-G-SF showed good discriminatory power based on receiver operating characteristic curve analysis in both studies. These results support the utility of the GAS-G-SF as a brief assessment measure for anxiety.

Physiological monitoring in the complex multimorbid heart failure patient - Conclusions.

Comorbidities are increasingly recognized as crucial components of the heart failure syndrome. Main specific challenges are polypharmacy, poor adherence to treatments, psychological aspects, and the need of monitoring after discharge. The chronic multimorbid patient therefore represents a specific heart failure phenotype that needs an appropriate and continuous management over time. This supplement issue covers the key points of a series of meeting coordinated by the Heart Failure Association of the European Society of Cardiology (ESC), that have discussed the issues surrounding the effective monitoring of our ever more complex and multimorbid heart failure patients. Here, we present an overview of the complex issues from a healthcare delivery perspective.

Ventricular arrhythmias and myocardial inflammation: Long-term follow-up of patients with suspected myocarditis.

BACKGROUND: Inflammatory heart disease is known to be associated with ventricular arrhythmias (VA) and impaired ventricular function at presentation or during follow-up. We aimed to investigate the need for implanted cardioverter defibrillator (ICD) due to ventricular dysfunction and occurrence of VA during long-term follow-up in patients admitted with suspected myocarditis. METHODS: Between 2000 and 2016, 191 patients (age 43 ±â€¯13 years, 71% male, mean left ventricular ejection fraction (LVEF) 33 ±â€¯15%) with clinically suspected myocarditis, who underwent endomyocardial biopsies (EMB), were prospectively enrolled and followed up in 6-months-intervals (median follow-up was 83 (49-156) months). The primary endpoint was deterioration of cardiac function (LVEF ≤ 35%) or occurrence of VA leading to ICD implantation. RESULTS: According to EMB results, patients were stratified in three diagnostic groups: acute myocarditis (5%), chronic myocarditis (50%) and dilated cardiomyopathy (DCM) (45%). An ICD implantation was performed in 58 patients (30%, n = 38 for primary prevention). Besides LVEF at baseline, chronic myocardial inflammation was the only independent predictor of ICD implantation for primary prevention (hazard ratio 2.48 (95% confidence interval 1.02-5.5); p = 0.045). VA requiring ICD therapy occurred in 29 of 58 patients (50%) after a median of 14 (2-37) months without a significant difference between presence and absence of myocardial inflammation. CONCLUSIONS: Nearly one third of patients with suspected myocarditis require an ICD due to impaired LVEF or occurrence of VA. Half of these patients experienced VA with adequate ICD therapy.

Screening, diagnosis and treatment of iron deficiency in chronic heart failure: putting the 2016 European Society of Cardiology heart failure guidelines into clinical practice.

Iron deficiency is common in patients with chronic heart failure (CHF) and is associated with reduced exercise performance, impaired health-related quality of life and an increased risk of mortality, irrespective of whether or not anaemia is present. Iron deficiency is a serious but treatable condition. Several randomized controlled clinical trials have demonstrated the ability of intravenous (IV) iron, primarily IV ferric carboxymaltose (FCM), to correct iron deficiency in patients with heart failure with reduced ejection fraction (HFrEF), resulting in improvements in exercise performance, CHF symptoms and health-related quality of life. The importance of addressing the issue of iron deficiency in patients with CHF is reflected in the 2016 European Society of Cardiology (ESC) heart failure guidelines, which recognize iron deficiency as an important co-morbidity, independent of anaemia. These guidelines recommend that all newly diagnosed heart failure patients are routinely tested for iron deficiency and that IV FCM should be considered as a treatment option in symptomatic patients with HFrEF and iron deficiency (serum ferritin < 100 µg/L, or ferritin 100-299 µg/L and transferrin saturation < 20%). Despite these specific recommendations, there is still a lack of practical, easy-to-follow advice on how to diagnose and treat iron deficiency in clinical practice. This article is intended to complement the current 2016 ESC heart failure guidelines by providing practical guidance to all health care professionals relating to the procedures for screening, diagnosis and treatment of iron deficiency in patients with CHF.

[Iron deficiency in heart failure. A new diagnostic therapy algorithm - evidence-tested and workable]. / Eisenmangel bei Herzinsuffizienz ­ neuer Diagnose-Therapie-Algorithmus, evidenzgeprüft und praktikabel.

BACKGROUND: Iron deficiency is a diagnostic and therapy-requiring comorbidity in heart failure with a negative impact on the prognosis. Even without signs of anemia, iron deficiency can lead to reduced performance with physical weakness and dyspnoea in patients with chronic heart failure. METHOD: Well-known cardiologists discussed this at an expert meeting on the topic of iron deficiency in heart failure. RESULTS AND CONCLUSIONS: Despite the high relevance for patients' outcome, this complication is still under-addressed, although specific diagnosis and effective therapy are possible and are also recommended in current ESC guidelines. A new evidence-tested algorithm should now help to facilitate diagnosis and therapy in everyday practice. The prerequisite is that it can be well integrated into clinical routine.

The first post-cardiac injury syndrome reported following transcatheter aortic valve implantation: a case report.

BACKGROUND: Post-cardiac injury syndrome is a form of secondary pericarditis with or without pericardial effusion, which typically occurs weeks to months following an injury to the heart or pericardium. Disease activity can be followed with serial testing of inflammatory markers e.g. C-reactive protein (CRP) and/or sedimentation rate, electrocardiogram, and echocardiography. CASE SUMMARY: A 79-year-old woman was admitted with chest pain, dyspnoea at rest, cough, and low degree fever. The patient had undergone transcatheter aortic valve implantation (TAVI) 6 months before admission. Inflammatory markers were increased and a chest X-ray and computed tomography (CT) showed a minimal left pleural effusion. An empirical antibiotic treatment and ibuprofen to control chest pain were started on the presumption of an acute bronchitis. Despite 15 days of different antibiotic protocols the markers of inflammation remained increased. A positron emission tomography with computed tomography and cardiac magnetic resonance imaging showed signs of an aseptic pericarditis. After having excluded any infectious, metabolic, drug-induced or neoplastic genesis we considered the diagnosis of late onset autoimmune-mediated pericarditis. Subsequently, treatment was promptly initiated with colchicine and prednisone. The patient reported clinical improvement in the following days and the CRP value continuously decreased. DISCUSSION: To the best of our knowledge, this is the first reported case of post-cardiac injury syndrome after TAVI. It should be considered in those patients who have persistent chest pain, fever, fatigue, and elevated inflammatory markers after a TAVI procedure, even though it may occur weeks or months after the intervention. A triple therapy with colchicine, ibuprofen, and low-dosage steroids may be used for persistent symptoms.

Physical and mental recovery after conventional aortic valve surgery.

OBJECTIVE: Physical and mental recovery are important factors to consider in the treatment of aortic valve disease, and the process of recovery is not well known. We investigated the course of physical and mental recovery directly after conventional aortic valve surgery. METHODS: In a longitudinal study, 60 patients undergoing elective aortic valve surgery were studied preoperatively and at intervals of 4 weeks after aortic valve surgery. The last measurement was taken 6 months postoperatively. Measurements included the 6-minute walk test and N-terminal pro-B-type natriuretic peptide. Mental recovery was assessed by the Short Form Health Survey and the Hospital Anxiety and Depression Scale. All parameters were compared with published healthy norms. RESULTS: All parameters except for the anxiety score showed a significant decline after the first postoperative measurement at 1 week after aortic valve surgery. The baseline level was restored at 1 to 3 weeks (anxiety, depression, mental quality of life, Borg scale), 4 to 6 weeks (6-minute walk test, physical quality of life), and 9 weeks (N-terminal pro-B-type natriuretic peptide) after the first postoperative week. Significantly better values than preoperatively for the first time were reached at 2 to 3 weeks (anxiety, depression, mental quality of life), 5 weeks (6-minute walk test), 8 weeks (physical quality of life), and 12 weeks (N-terminal pro-B-type natriuretic peptide) after the first postoperative week. At 3 months postoperatively, significant improvements (P < .001) were seen in walk distance (+212 m), dyspnea (-1.11), physical (+12.38) and mental quality of life (+7.71), anxiety (-3.74), and depression (-3.62) compared with the first week postoperatively. At 6 months postoperatively, all parameters were significantly improved compared with preoperative data and, except for the N-terminal pro-B-type natriuretic peptide value, significantly better or equal compared with published healthy norms. CONCLUSIONS: After conventional aortic valve surgery, the most pronounced recovery was seen in the first 6 weeks postoperatively. Physical quality of life and N-terminal pro-B-type natriuretic peptide required a prolonged time for a complete recovery.

Vena cava compression syndrome in patients with obesity presenting with edema and thrombosis.

OBJECTIVE: Obesity is a risk factor for cardiovascular disease and venous thrombosis. Previous studies have shown that in late pregnancy a compression of the inferior vena cava (VCI) leads to a hypotensive syndrome. The objective of this study was to explore the correlation between obesity and an elevated pressure in the VCI simulating obesity-induced vena cava compression syndrome. METHODS: A left and right heart catheterization was performed in 29 patients. After right atrial pressure measurement, the catheter was pulled back through the VCI, and the pressure gradient between the thoracic and abdominal vena cava was measured. We determined the correlation between the BMI and the pressure gradient. RESULTS: In 29 patients, a high BMI was associated with an increased pressure gradient between the thoracic and abdominal vena cava (r = 0.66). This correlation was particularly close in patients with a BMI >30 kg/m(2) (P = 0.0008). Two patients had complications such as recurrent thrombosis, with one of them having the highest pressure gradient of 16 mm Hg. CONCLUSIONS: Because mechanical obstruction of the VCI leads to an increased risk for venous thrombosis in patients with obesity, this finding needs to be considered in the decision-making for interventional treatments like bariatric surgery.

Predictors of outcome in patients with parvovirus B19 positive endomyocardial biopsy.

OBJECTIVE: Primary objective was to establish the prognostic value of the myocardial load of PVB19 genomes in patients presenting for work-up of myocarditis and/or unclear cardiomyopathy in comparison to clinical, and CMR parameters. METHODS: 108 consecutive patients who underwent EMB because of suspected myocarditis and/or unclear cardiomyopathy, and had evidence of myocardial PVB19 genome, were enrolled. Primary endpoint was all-cause mortality; secondary endpoint was a composite of cardiac mortality and hospitalization for heart failure. RESULTS: Mean LV-EF was 40%. We found n = 27 patients to have a viral load ≥ 500 GE (IQR 559-846), n = 72 had 100-499 GE, and n = 9 had <100 GE. Immunohistology revealed chronic myocarditis in n = 66, acute myocarditis in n = 1, DCM in n = 17, PVB19 genome only in n = 13, and other pathologies in n = 11. During follow-up 11 patients died, two suffered SCD but were successfully shocked by ICD, and 21 were hospitalized for heart failure. Interestingly, not the viral load, but functional parameters such as LV-EF, LV-EDV (endpoint 2), as well as the histologic diagnosis of DCM and the presence of LGE (for all endpoints) reached statistical significance. In fact, the presence of LGE yields an odds-ratio for a lethal event of 8.56 (endpoint 1), and of 5.52 for endpoint 2. No patient with normal LV-EF, or the absence of LGE, suffered cardiac death during long-term follow-up. CONCLUSION: The viral load of PVB19 genomes in the myocardium is not related to the long-term outcome. Furthermore, this study suggests a growing role of imaging for risk stratification in non-ischemic myocardial disease.

Angiopoietin-2 and outcome in patients with acute decompensated heart failure.

PURPOSE: Angiopoietin-2 (Ang-2) impairs endothelial integrity. The association of Ang-2 in the presence of oedema and outcome of patients with acute decompensated heart failure (ADHF) has not been investigated. METHODS AND RESULTS: Angiopoietin-2 was measured in 132 ADHF patients, which were included in a monocentric, prospective trial (Clinicaltrials.gov: NCT01429857). Primary endpoint was all-cause death at 6-months. 20 healthy persons served as control group (HC). In ADHF patients, mean Ang-2 concentration at admission was significantly increased compared to HC (2,111 ± 117 vs. 971 ± 46 pg/ml, p = 0.0002). Ang-2 was increased in patients with compared to those without peripheral oedema (2,294 ± 140 vs. 1,540 ± 170 pg/ml; p = 0.009) and in patients with NYHA class III or IV symptoms compared to those with NYHA class II symptoms (2,256 ± 132 vs. 1,341 ± 380 pg/ml, p = 0.023). During the 6-month follow-up, 10 patients died. In survivors, Ang-2 significantly decreased at discharge compared to admission (2,046 ± 118 vs. 1,431 ± 93 pg/ml; p < 0.0001). Non-survivors showed no difference between Ang-2 concentration at admission and discharge (3,296 ± 594 vs. 2,909 ± 536 pg/ml). Ang-2 concentrations at discharge above 2,500 pg/ml were associated with an increased risk of death compared to Ang-2 concentrations below this threshold (Hazard ratio 8.8; 95 % confidence interval; 2.48-31.16, p < 0.001). CONCLUSION: In ADHF patients, Ang-2 is significantly increased compared to healthy controls, shows a relationship in the presence of oedema and is a predictor of poor outcome.

Position paper on the importance of psychosocial factors in cardiology: Update 2013.

BACKGROUND: The rapid progress of psychosomatic research in cardiology and also the increasing impact of psychosocial issues in the clinical daily routine have prompted the Clinical Commission of the German Heart Society (DGK) to agree to an update of the first state of the art paper on this issue which was originally released in 2008. METHODS: The circle of experts was increased, general aspects were implemented and the state of the art was updated. Particular emphasis was dedicated to coronary heart diseases (CHD), heart rhythm diseases and heart failure because to date the evidence-based clinical knowledge is most advanced in these particular areas. Differences between men and women and over the life span were considered in the recommendations as were influences of cognitive capability and the interactive and synergistic impact of classical somatic risk factors on the affective comorbidity in heart disease patients. RESULTS: A IA recommendation (recommendation grade I and evidence grade A) was given for the need to consider psychosocial risk factors in the estimation of coronary risks as etiological and prognostic risk factors. Furthermore, for the recommendation to routinely integrate psychosocial patient management into the care of heart surgery patients because in these patients, comorbid affective disorders (e.g. depression, anxiety and post-traumatic stress disorder) are highly prevalent and often have a malignant prognosis. A IB recommendation was given for the treatment of psychosocial risk factors aiming to prevent the onset of CHD, particularly if the psychosocial risk factor is harmful in itself (e.g. depression) or constrains the treatment of the somatic risk factors. Patients with acute and chronic CHD should be offered anti-depressive medication if these patients suffer from medium to severe states of depression and in this case medication with selective reuptake inhibitors should be given. In the long-term course of treatment with implanted cardioverter defibrillators (ICDs) a subjective health technology assessment is warranted. In particular, the likelihood of affective comorbidities and the onset of psychological crises should be carefully considered. CONCLUSIONS: The present state of the art paper presents an update of current empirical evidence in psychocardiology. The paper provides evidence-based recommendations for the integration of psychosocial factors into cardiological practice and highlights areas of high priority. The evidence for estimating the efficiency for psychotherapeutic and psychopharmacological interventions has increased substantially since the first release of the policy document but is, however, still weak. There remains an urgent need to establish curricula for physician competence in psychodiagnosis, communication and referral to ensure that current psychocardiac knowledge is translated into the daily routine.

Diagnostic and prognostic validity of different biomarkers in patients with suspected myocarditis.

BACKGROUND: Myocarditis might be associated with increased markers of myocardial injury. However, data on novel biomarkers, such as high-sensitive Troponin T (hs-TnT) or Copeptin, are lacking. This study aimed to determine the diagnostic and prognostic utility of biomarkers in patients with suspected myocarditis. METHODS: Seventy patients with clinically suspected myocarditis (age 43.4 ± 14 years, 76 % male, ejection fraction 36.9 ± 17.8) underwent endomyocardial biopsy (EMB) and were followed for 7.5 (2-21) months. At the time of EMB, blood samples to evaluate concentrations of hs-TnT, Copeptin, NT-proBNP and mid-regional pro-adrenomedullin (MR-proADM) were collected. RESULTS: According to EMB, 6 patients were diagnosed with acute myocarditis (AM) and 36 patients with chronic myocarditis (CM). In 28 patients, EMB revealed no myocardial inflammation (NM). Acute myocarditis was associated with the highest concentrations of hs-TnT compared to other groups (AM 262.9 pg/ml (61.4-884.2); CM 20.4 pg/ml (15.6-20.4); NM 19.5 pg/ml (13.8-50.7); p < 0.0001). No significant differences existed in the Copeptin, NT-proBNP, and MR-proADM concentrations between the groups. The concentration of hs-TnT was significantly higher in myocarditis when myocardial viral genome was detected (37.4 pg/ml (21.9-163.6) vs. 20 pg/ml (14-44.4); p = 0.042). During follow-up, only NT-proBNP in the highest quartile (>4,225 ng/ml) was predictive for cardiac death or heart transplantation (hazard ratio 9.2; 95% confidence interval 1.7-50; p = 0.011). CONCLUSIONS: Biopsy-proven acute and viral myocarditis is associated with elevated concentrations of hs-TnT. Elevated hs-TnT is highly suggestive of acute myocarditis, if other causes of increased myocardial necrosis markers such as myocardial infarction have been systematically excluded.

Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension.

Increased renal resistive index and urinary albumin excretion are markers of hypertensive end-organ damage and renal vasoconstriction involving increased sympathetic activity. Catheter-based sympathetic renal denervation (RD) offers a new approach to reduce renal sympathetic activity and blood pressure in resistant hypertension. The influence of RD on renal hemodynamics, renal function, and urinary albumin excretion has not been studied. One hundred consecutive patients with resistant hypertension were included in the study; 88 underwent interventional RD and 12 served as controls. Systolic, diastolic, and pulse pressure, as well renal resistive index in interlobar arteries, renal function, and urinary albumin excretion, were measured before and at 3 and 6 months of follow-up. RD reduced systolic, diastolic, and pulse pressure at 3 and 6 months by 22.7/26.6 mm Hg, 7.7/9.7 mm Hg, and 15.1/17.5 mm Hg (P for all <0.001), respectively, without significant changes in the control group. SBP reduction after 6 months correlated with SBP baseline values (r=-0.46; P<0.001). There were no renal artery stenoses, dissections, or aneurysms during 6 months of follow-up. Renal resistive index decreased from 0.691±0.01 at baseline to 0.674±0.01 and 0.670±0.01 (P=0.037/0.017) at 3- and 6-month follow-up. Mean cystatin C glomerular filtration rate and urinary albumin excretion remained unchanged after RD; however, the number of patients with microalbuminuria or macroalbuminuria decreased. RD reduced blood pressure, renal resistive index, and incidence of albuminuria without adversely affecting glomerular filtration rate or renal artery structure within 6 months and appears to be a safe and effective therapeutic approach to lower blood pressure in patients with resistant hypertension.

Blood pressure and heart rate predict outcome in patients acutely admitted with suspected myocarditis without previous heart failure.

OBJECTIVE: The study investigated the prognostic impact of blood pressure and heart rate in patients acutely admitted with suspected myocarditis without previous heart failure who underwent endomyocardial biopsy. METHODS AND RESULTS: In our prospectively planned study SBP, DBP, mean arterial blood pressure (MAP) and ECGs on admission were analyzed retrospectively in 175 patients with suspected myocarditis, who underwent endomyocardial biopsy between 1994 and 2007. Patients were followed up for a median of 53 ±â€Š41 months, corresponding to a total follow-up of 9337 patient months. The primary endpoint was the time to cardiac death or heart transplantation, which occurred in 39 patients (22%). Baseline SBP was inversely associated with primary endpoint occurrence. Per 1 mmHg increase in SBP, the hazard ratio for the primary endpoint decreased by 4.3% [hazard ratio = 0.96, confidence interval (CI) = 0.94-0.98, P < 0.001]. The increased risk at a SBP below the mean value was confirmed after adjusting for the known independent predictors immunohistological signs of inflammation in biopsy samples, New York Heart Association functional class, and lack of ß-blocker treatment (hazard ratio = 2.78, CI = 1.25-6.18, P = 0.012). In the presence of all risk predictors, hazard ratio for primary endpoint was 4.97 (CI = 2.28-10.83, P < 0.001). In a subgroup analysis of patients without ß-blocker treatment, atrial fibrillation or pacemaker, a high heart rate was also associated with poor outcome (hazard ratio = 2.92, CI = 1.02-8.29, P = 0.045). CONCLUSION: In patients with suspected myocarditis without previous chronic heart failure low SBP, DBP and MAP were predictors of poor outcome. However, in patients not treated with ß-blockers, a high heart rate was a predictor for cardiac death or heart transplantation.

Update on myocarditis.

Myocarditis is an inflammatory disease of the heart frequently resulting from viral infections and/or post-viral immune-mediated responses. It is one of the important causes of dilated cardiomyopathy worldwide. The diagnosis is presumed on clinical presentation and noninvasive diagnostic methods such as cardiovascular magnetic resonance imaging. Endomyocardial biopsy remains the gold standard for in vivo diagnosis of myocarditis. The therapeutic and prognostic benefits of endomyocardial biopsy results have recently been demonstrated in several clinical trials. Although remarkable advances in diagnosis, understanding of pathophysiological mechanisms, and treatment of acute myocarditis were gained during the last years, no standard treatment strategies could be defined as yet, apart from standard heart failure therapy and physical rest. In severe cases, mechanical support or heart transplantation may become necessary. There is some evidence that immunosuppressive and immunomodulating therapy are effective for chronic, virus-negative inflammatory cardiomyopathy. Further investigations by controlled, randomized studies are needed to definitively determine their role in the treatment of myocarditis.

Virus serology in patients with suspected myocarditis: utility or futility?

AIMS: Serological analyses of viral infection in suspected myocarditis are still widely used, although convincing evidence for their value is lacking. We determined prospectively the diagnostic value of virus serology in comparison with endomyocardial biopsy (EMB) including viral genome detection and immunohistochemistry in patients with clinically suspected myocarditis. METHODS AND RESULTS: Virus serology and state-of-the-art evaluation of EMB were performed in 124 patients (age 40 ± 15 years) with suspected myocarditis. Endomyocardial biopsy was studied for inflammation with histological and immunohistological criteria. The viral genome was detected in the myocardium by polymerase chain reaction. Acute viral infection with enterovirus, adenovirus, parvovirus B19, cytomegalovirus, human herpesvirus, and Epstein-Barr virus was diagnosed by IgM or IgA in the initial sample or IgG seroconversion in the follow-up sample. Immunohistological signs of inflammation were present in 54 patients. The viral genome was detected in the myocardium of 58 patients (47%). In 20 patients (16%), acute viral infection was diagnosed by serology. Only in 5 out of 124 patients (4%), there was serological evidence of an infection with the same virus that was detected by EMB. Sensitivity and specificity of virus serology were 9 and 77%, respectively. The positive predictive value was 25% and the negative predictive value was 49%. The lack of correlation between serology and EMB remained also for patients with biopsy-proven myocarditis and patients with time from initial symptoms to EMB procedure of ≤1 month. CONCLUSIONS: For patients with suspected myocarditis, virus serology has no relevance for the diagnosis of myocardial infection. Endomyocardial biopsy remains the gold standard in the diagnostic of viral myocarditis.