Julia Schumm

Long-Term Follow-Up of Biopsy-Proven Viral Myocarditis Predictors of Mortality and Incomplete Recovery

OBJECTIVES This study sought to evaluate the long-term mortality in patients with viral myocarditis, and to establish the prognostic value of various clinical, functional, and cardiovascular magnetic resonance (CMR) parameters. BACKGROUND Long-term mortality of viral myocarditis, as well as potential risk factors for poor clinical outcome, are widely unknown. METHODS A total of 222 consecutive patients with biopsy-proven viral myocarditis and CMR were enrolled. A total of 203 patients were available for clinical follow-up, and 77 patients underwent additional follow-up CMR. The median follow-up was 4.7 years. Primary endpoints were all-cause mortality and cardiac mortality. RESULTS We found a relevant long-term mortality in myocarditis patients (19.2% all cause, 15% cardiac, and 9.9% sudden cardiac death [SCD]). The presence of late gadolinium enhancement (LGE) yields a hazard ratio of 8.4 for all-cause mortality and 12.8 for cardiac mortality, independent of clinical symptoms. This is superior to parameters like left ventricular (LV) ejection fraction, LV end-diastolic volume, or New York Heart Association (NYHA) functional class, yielding hazard ratios between 1.0 and 3.2 for all-cause mortality and between 1.0 and 2.2 for cardiac mortality. No patient without LGE experienced SCD, even if the LV was enlarged and impaired. When focusing on the subgroup undergoing follow-up CMR, we found an initial NYHA functional class >I as the best independent predictor for incomplete recovery (p = 0.03). CONCLUSIONS Among our population with a wide range of clinical symptoms, biopsy-proven viral myocarditis is associated with a long-term mortality of up to 19.2% in 4.7 years. In addition, the presence of LGE is the best independent predictor of all-cause mortality and of cardiac mortality. Furthermore, initial presentation with heart failure may be a good predictor of incomplete long-term recovery.

CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis.

OBJECTIVES This study aimed to demonstrate that the presence of late gadolinium enhancement (LGE) is a predictor of death and other adverse events in patients with suspected cardiac sarcoidosis. BACKGROUND Cardiac sarcoidosis is the most important cause of patient mortality in systemic sarcoidosis, yielding a 5-year mortality rate between 25% and 66% despite immunosuppressive treatment. Other groups have shown that LGE may hold promise in predicting future adverse events in this patient group. METHODS We included 155 consecutive patients with systemic sarcoidosis who underwent cardiac magnetic resonance (CMR) for workup of suspected cardiac sarcoid involvement. The median follow-up time was 2.6 years. Primary endpoints were death, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator (ICD) discharge. Secondary endpoints were ventricular tachycardia (VT) and nonsustained VT. RESULTS LGE was present in 39 patients (25.5%). The presence of LGE yields a Cox hazard ratio (HR) of 31.6 for death, aborted sudden cardiac death, or appropriate ICD discharge, and of 33.9 for any event. This is superior to functional or clinical parameters such as left ventricular (LV) ejection fraction (EF), LV end-diastolic volume, or presentation as heart failure, yielding HRs between 0.99 (per % increase LVEF) and 1.004 (presentation as heart failure), and between 0.94 and 1.2 for potentially lethal or other adverse events, respectively. Except for 1 patient dying from pulmonary infection, no patient without LGE died or experienced any event during follow-up, even if the LV was enlarged and the LVEF severely impaired. CONCLUSIONS Among our population of sarcoid patients with nonspecific symptoms, the presence of myocardial scar indicated by LGE was the best independent predictor of potentially lethal events, as well as other adverse events, yielding a Cox HR of 31.6 and of 33.9, respectively. These data support the necessity for future large, longitudinal follow-up studies to definitely establish LGE as an independent predictor of cardiac death in sarcoidosis, as well as to evaluate the incremental prognostic value of additional parameters.

European cardiovascular magnetic resonance (EuroCMR) registry – multi national results from 57 centers in 15 countries

BackgroundThe EuroCMR registry sought to evaluate indications, image quality, safety and impact on patient management of clinical routine CMR in a multi-national European setting. Furthermore, interim analysis of the specific protocols should underscore the prognostic potential of CMR.MethodsMulti-center registry with consecutive enrolment of patients in 57 centers in 15 countries. More than 27000 consecutive patients were enrolled.ResultsThe most important indications were risk stratification in suspected CAD/Ischemia (34.2%), workup of myocarditis/cardiomyopathies (32.2%), as well as assessment of viability (14.6%). Image quality was diagnostic in more than 98% of cases. Severe complications occurred in 0.026%, always associated with stress testing. No patient died during or due to CMR. In 61.8% CMR findings impacted on patient management. Importantly, in nearly 8.7% the final diagnosis based on CMR was different to the diagnosis before CMR, leading to a complete change in management. Interim analysis of suspected CAD and risk stratification in HCM specific protocols revealed a low rate of adverse events for suspected CAD patients with normal stress CMR (1.0% per year), and for HCM patients without LGE (2.7% per year).ConclusionThe most important indications in Europe are risk stratification in suspected CAD/Ischemia, work-up of myocarditis and cardiomyopathies, as well as assessment of viability. CMR imaging is a safe procedure, has diagnostic image quality in more than 98% of cases, and its results have strong impact on patient management. Interim analyses of the specific protocols underscore the prognostic value of clinical routine CMR in CAD and HCM.Condensed abstractThe EuroCMR registry sought to evaluate indications, image quality, safety and impact on patient management of clinical routine CMR in a multi-national European setting in a large number of cases (n > 27000). Based on our data CMR is frequently performed in European daily clinical routine. The most important indications in Europe are risk stratification in suspected CAD/Ischemia, work-up of myocarditis and cardiomyopathies, as well as assessment of viability. CMR imaging is a safe procedure, has diagnostic image quality in more than 98% of cases, and its results have strong impact on patient management. Interim analyses of the specific protocols underscore the prognostic value of clinical routine CMR in CAD and HCM.

Cardiovascular magnetic resonance risk stratification in patients with clinically suspected myocarditis

BackgroundThe diagnosis of myocarditis is challenging due to its varying clinical presentation. Since myocarditis can be associated with significant 5-year mortality, and postmortem data show myocarditis in almost 10% of all adults suffering sudden cardiac death, individual risk stratification for patients with suspected myocarditis is of great clinical interest. We sought to demonstrate that patients with clinically suspected myocarditis and a normal cardiovascular magnetic resonance (CMR) according to our definition have a good prognosis, independent of their clinical symptoms and other findings.MethodsProspective clinical long-term follow-up of consecutive patients undergoing CMR for work-up of clinically suspected myocarditis at our institution in 2007-2008.ResultsFollow-up was available for n = 405 patients (all-comers, 54.8% inpatients, 38% outpatient referrals from cardiologists). Median follow-up time was 1591 days. CMR diagnosis was “myocarditis” in 28.8%, “normal” in 55.6% and “other pathology” in 15.6%. Normal CMR was defined as normal left ventricular (LV) volumes and normal left ventricular ejection fraction (LV-EF) in the absence of late Gadolinium Enhancement (LGE). The overall mortality was 3.2%. There were seven cardiac deaths during follow-up, in addition one aborted SCD and two patients had appropriate internal cardioverter defibrillator (ICD) shocks – all of these occurred in patients with abnormal CMR. Kaplan-Meier analysis with log-rank test showed significant difference for major adverse cardiac events (cardiac death, sudden cardiac death (SCD), ICD discharge, aborted SCD) between patients with normal and abnormal CMR (p = 0.0003).ConclusionIn our unselected population of consecutive patients referred for CMR work-up of clinically suspected myocarditis, patients with normal CMR have a good prognosis independent of their clinical symptoms and other findings.

Serum levels of large tenascin‐C variants, matrix metalloproteinase‐9, and tissue inhibitors of matrix metalloproteinases in concentric versus eccentric left ventricular hypertrophy

Chronic hypertension may cause left ventricular hypertrophy (LVH). The role of matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), and tenascin‐C (Tn‐C) splice variants in concentric vs. eccentric left ventricular remodelling has not been investigated.

Incremental Value of Late Gadolinium Enhancement for Management of Patients With Hypertrophic Cardiomyopathy

Cardiac magnetic resonance with late gadolinium enhancement (LGE) is a well-established method for in vivo detection of myocardial scarring. Several recent studies have investigated the prognostic value of LGE in patients with hypertrophic cardiomyopathy (HC). We discuss the prevalence and patterns of scarring in HC and its pathophysiologic significance, with focus on ventricular arrhythmias and sudden cardiac death. The available evidence that myocardial scar demonstrated by LGE is a good independent predictor of cardiac mortality in HC is summed up. Recommendations of current guidelines for prevention of sudden cardiac death in HC are discussed with regard to recent results, and the significance of LGE as an emerging risk factor is pointed out. In conclusion, it is demonstrated that LGE has incremental value in addition to clinical risk factors for risk stratification and management of patients with HC.

Favorable Course of Pericardial Angiosarcoma Under Paclitaxel Followed by Pazopanib Treatment Documented by Cardiovascular Magnetic Resonance Imaging

A 31-year–old white male patient was transferred from a local district hospital for suspected pericardial mass. Two months earlier he had been admitted there for worsening shortness of breath and subsequently was diagnosed with a large pericardial effusion. He had no other pertinent past medical history. After pericardiocentesis (1.5 L) there was no evidence of malignant cells on cytology, and a computed tomography scan did not reveal any abnormality. Thus, the incident was interpreted as (viral) infectious pericarditis and the patient clinically improved under anti-inflammatory medication within 4 weeks. After that, while on a holiday in Tunisia, he again reported worsening shortness of breath. On day 6 of his holiday, he suddenly passed out and was admitted to a local hospital for unexplained syncope, where again a large pericardial effusion was seen. This time, after another pericardiocentesis (1 L), a pericardial mass was suspected …

Comparison of exercise electrocardiography and stress perfusion CMR for the detection of coronary artery disease in women.

BackgroundExercise electrocardiography (ECG) is frequently used in the work-up of patients with suspected coronary artery disease (CAD), however the accuracy is reduced in women. Cardiovascular magnetic resonance (CMR) stress testing can accurately diagnose CAD in women. To date, a direct comparison of CMR to ECG has not been performed.Methods and resultsWe prospectively enrolled 88 consecutive women with chest pain or other symptoms suggestive of CAD. Patients underwent a comprehensive clinical evaluation, exercise ECG, a CMR stress test including perfusion and infarct imaging, and x-ray coronary angiography (CA) within 24 hours. CAD was defined as stenosis ≥70% on quantitative analysis of CA.Exercise ECG, CMR and CA was completed in 68 females (age 66.4 ± 8.8 years, number of CAD risk factors 3.5 ± 1.4). The prevalence of CAD on CA was 29%. The Duke treadmill score (DTS) in the entire group was −3.0 ± 5.4 and was similar in those with and without CAD (−4.5 ± 5.8 and −2.4 ± 5.1; P = 0.12). Sensitivity, specificity and accuracy for CAD diagnosis was higher for CMR compared with exercise ECG (sensitivities 85% and 50%, P = 0.02, specificities 94% and 73%, P = 0.01, and accuracies 91% and 66%, P = 0.0007, respectively). Even after applying the DTS the accuracy of CMR was higher compared to exercise ECG (area under ROC curve 0.94 ± 0.03 vs 0.56 ± 0.07; P = 0.0001).ConclusionsIn women with intermediate-to-high risk for CAD who are able to exercise and have interpretable resting ECG, CMR stress perfusion imaging has higher accuracy for the detection of relevant obstruction of the epicardial coronaries when directly compared to exercise ECG.

T1 mapping as new diagnostic technique in a case of acute onset of biopsy-proven viral myocarditis

To the editor: We have seen with great interest that quantitative T1-mapping techniques are increasingly used in CMR research. This letter draws attention to the fact that T1 mapping may also aid CMR diagnosis of acute myocarditis in a routine clinical setting. A 56-year-old white male patient was referred by his general practitioner for work-up of elevated troponin T (399 pg/ml; normal \14 pg/ml) found during routine check-up. The patient reported no angina, palpitations or dyspnea. However, 2 days ago he briefly had some chills and stayed in bed for 1 day, but after that he felt better and had been to work normally. The initial ECG was without abnormalities except sinus tachycardia (108/min.), but within hours the patient developed T-wave inversions in II, III and aVF, which has been described as one of the typical ECG changes in acute myocarditis [1]. High-sensitivity troponin T rose to up to 1,967 pg/ml during the next 42 h. Inflammatory markers were also elevated (max. CRP 23.6 mg/dl; normal\0.6 mg/dl, ESR 84 mm/h, leucocytes 12.9 GIGA/l). Cardiovascular MR (CMR) for work-up of suspected myocarditis was performed using a 1.5T Magnetom Aera (Siemens Health Care, Germany). Cine-SSFPs revealed mildly impaired LV-EF (52 %) with hypokinesia and swelling in the basal and midventricular posterolateral wall (Fig. 1). Breath-hold T2-weighted imaging using blackblood TIRM was performed before gadolinium contrast administration and demonstrated myocardial signal increase located in the posterolateral wall matching the area of the wall motion abnormality described above (Fig. 1). T1 mapping was obtained with a modified looklocker inversion-recovery sequence (MOLLI) during breath-hold before and after administration of gadolinium. Late gadolinium enhancement (LGE) images were acquired on average 5–10 min after contrast administration (gadopentetat-dimeglumin 0.15 mmol/kg) using segmented IR-FLASH constantly adjusting inversion time. LGE revealed subepicardial enhancement of the posterolateral wall, which is frequently seen in myocarditis (Fig. 1). The pre-contrast T1 mapping demonstrated significantly elevated T1 values in the affected region (1132 ± 47 ms in the posterolateral vs. 870 ± 41 ms in the septal wall, T1 of blood pool 1419 ± 32 ms). CineSSFP, pre-contrast T1 mapping and T2-weighted darkblood images of corresponding short-axis slices can be compared in Fig. 2. Figure 3 displays the post-contrast T1 mapping and the matching LGE short-axis image, demonstrating a good correlation of the shortened T1 after gadolinium and the LGE in the subepicardial posterolateral region. Significant coronary stenosis was ruled out invasively. Multiple endomyocardial biopsies (n = 11) were taken at different locations from the midventricular and apical parts of the left ventricle to exclude bacterial, giant cell or other rheumatic forms of myocarditis. Histopathological workup confirmed the diagnosis of viral myocarditis with infiltrations of CD3-positive leucocytes ([14/mm), as well as signs of myocyte damage and beginning fibrosis. Nested PCR detected human herpesvirus 6 (HHV6)-specific DNA sequences localized in myocardial cells, but not in peripheral leucocyte preparations or plasma, confirming viral myocarditis. Bacterial or rheumatic forms of myocarditis could be excluded as described before [2]. J. Schumm S. Greulich (&) U. Sechtem H. Mahrholdt Department of Cardiology, Robert Bosch Medical Center, Auerbachstrasse 110, 70376 Stuttgart, Germany e-mail: simon.greulich@rbk.de

An Unusual Case of Progressive Shock and Highly Elevated Procalcitonin Level

A 21-year-old man with signs and symptoms of rapidly progressive shock was admitted to the intensive care unit for treatment of suspected sepsis. Levels of inflammatory markers (including procalcitonin) were highly elevated, but no obvious focus of infection was apparent. Initial sepsis therapy included administration of broad-spectrum antibiotics, vasoconstrictors, and drotrecogin alfa. Cultures of blood, sputum, and urine showed no growth, and no viruses were detected. The random (no stimulation with corticotropin) cortisol level at admission was less than 25 nmol/L. Assays for autoantibodies to the adrenal cortex were strongly positive and confirmed the diagnosis of adrenal failure caused by Addison disease. After initiation of steroid therapy, the patient fully recovered. Although increased procalcitonin levels are considered a reliable and specific indicator of severe generalized infections and bacterial sepsis, elevated procalcitonin levels cannot be relied on when trying to differentiate between addisonian crisis and septic shock.