Predictors of Mortality in Patients With Biopsy-Proven Viral Myocarditis: 10-Year Outcome Data.

Background There is scarce data about the long-term mortality as well as the prognostic value of cardiovascular magnetic resonance and late gadolinium enhancement (LGE) in patients with biopsy-proven viral myocarditis. We sought to investigate: (1) mortality and (2) prognostic value of LGEcardiovascular magnetic resonance (location, pattern, extent, and distribution) in a >10-year follow-up in patients with biopsy-proven myocarditis. Methods and Results Two-hundred three consecutive patients with biopsy-proven viral myocarditis and cardiovascular magnetic resonance were enrolled; 183 patients were eligible for standardized follow-up. The median follow-up was 10.1 years. End points were all-cause death, cardiac death, and sudden cardiac death (SCD). We found substantial long-term mortality in patients with biopsy-proven myocarditis (39.3% all cause, 27.3% cardiac, and 10.9% SCD); 101 patients (55.2%) demonstrated LGE. The presence of LGE was associated with a more than a doubled risk of death (hazard ratio [HR], 2.40; 95% CI], 1.30-4.43), escalating to a HR of 3.00 (95% CI, 1.41-6.42) for cardiac death, and a HR of 14.79 (95% CI, 1.95-112.00) for SCD; all P≤0.009. Specifically, midwall, (antero-) septal LGE, and extent of LGE were highly associated with death, all P<0.001. Septal LGE was the best independent predictor for SCD (HR, 4.59; 95% CI, 1.38-15.24; P=0.01). Conclusions In patients with biopsy-proven viral myocarditis, the presence of midwall LGE in the (antero-) septal segments is associated with a higher rate of mortality (including SCD) compared with absent LGE or other LGE patterns, underlining the prognostic benefit of a distinct LGE analysis in these patients.

Electrocardiographic abnormalities and relative bradycardia in patients with hantavirus-induced nephropathia epidemica.

BACKGROUND: Nephropathia epidemica (NE), caused by Puumala virus (PUUV), is characterized by acute kidney injury (AKI) and thrombocytopenia. Cardiac involvement with electrocardiographic (ECG) abnormalities has been previously reported in NE; however, its prognostic value is unknown. Relative bradycardia is an important clinical sign in various infectious diseases, and previous smaller studies have described pulse-temperature deficit in patients with PUUV infection. METHODS: We performed a cross-sectional survey of 471 adult patients with serologically confirmed NE. Data were collected retrospectively from medical records and prospectively at follow-up visits. Patients for whom ECGs were recorded during the acute phase of disease were enrolled retrospectively (n=263). Three patients were excluded because of documented pre-existing ECG abnormalities prior to NE. All patients with ECG abnormalities during the acute phase underwent follow-up. RESULTS: A total of 46 patients had ECG abnormalities at the time of admission to hospital (18%). T-wave inversion was the most frequent ECG abnormality (n=31 patients), followed by ST segment changes (nine patients with elevation and six with depression). No major adverse cardiac events occurred during follow-up (median 37months; range 34-63months). Of note, ECG abnormalities reverted to normal in the majority of the patients during follow-up. During the acute phase of NE, 149 of 186 patients had relative bradycardia, without implications for disease course. CONCLUSIONS: Transient ECG abnormalities were detected in 18% of patients during acute NE but were not associated with negative cardiovascular outcome. Relative bradycardia was identified in 80% of the patients with acute NE.

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.

Impact of arrhythmia on diagnostic performance of adenosine stress CMR in patients with suspected or known coronary artery disease.

BACKGROUND: The diagnostic performance of adenosine stress cardiovascular magnetic resonance (CMR) in patients with arrhythmias presenting for work-up of suspected or known CAD is largely unknown, since most CMR studies currently available exclude arrhythmic patients from analysis fearing gating problems, or other artifacts will impair image quality. The primary aim of our study was to evaluate the diagnostic performance of adenosine stress CMR for detection of significant coronary stenosis in patients with arrhythmia presenting for 1) work-up of suspected coronary artery disease (CAD), or 2) work-up of ischemia in known CAD. METHODS: Patients with arrhythmia referred for work-up of suspected CAD or work-up of ischemia in known CAD undergoing adenosine stress CMR were included if they had coronary angiography within four weeks of CMR. RESULTS: One hundred fifty-nine patients were included (n = 64 atrial fibrillation, n = 87 frequent ventricular extrasystoles, n = 8 frequent supraventricular extrasystoles). Of these, n = 72 had suspected CAD, and n = 87 had known CAD. Diagnostic accuracy of the adenosine stress CMR for detection of significant CAD was 73 % for the entire population (sensitivity 72 %, specificity 76 %). Diagnostic accuracy was 75 % (sensitivity 80 %, specificity 74 %) in patients with suspected CAD, and 74 % (sensitivity 71 %, specificity 79 %) in the group with known CAD. For different types of arrhythmia, diagnostic accuracy of CMR was 70 % in the atrial fibrillation group, and 79 % in patients with ventricular extrasystoles. On a per coronary territory analysis, diagnostic accuracy of CMR was 77 % for stenosis of the left and 82 % for stenosis of the right coronary artery. CONCLUSION: The present data demonstrates good diagnostic performance of adenosine stress CMR for detection of significant coronary stenosis in patients with arrhythmia presenting for work-up of suspected CAD, or work-up of ischemia in known CAD. This holds true for a per patient, as well as for a per coronary territory analysis.

Extra cardiac findings in cardiovascular MR: why cardiologists and radiologists should read together.

PURPOSE: To assess prevalence and significance of extra cardiac findings (ECF) in clinical routine cardiovascular magnetic resonance (CMR) studies reported by cardiologists alone versus cardiologist and radiologist working together. METHODS: One-thousand-seventy-four consecutive patients presenting at our institution for CMR work-up of multiple cardiovascular disease entities were enrolled retrospectively in two groups (cardiologists reading alone vs. cardiologists and radiologist reading together). RESULTS: In 1,074 routine CMR studies a total of 357 ECF's were identified in 235 patients yielding a prevalence of 21.9 %. Of these 357 ECF's more than one-third were previously known. In the remaining 223 previously unknown findings 118 (52.9 %) were considered as major ECF's (92 patients), and 105 (47.1 %) were considered as minor ECF's (69 patients). Cardiologists reading alone reported 23 previously unknown ECF's in 23 patients, versus 200 previously unknown ECF in 138 patients by cardiologists and radiologists working together, p < 0.0001. Nevertheless, highly significant ECF's with major prognostic implications, such as the initial diagnosis of malignancy in an individual with no history of cancer, are extremely rare (n = 3, 0.3 %). Cardiologists alone, as well as cardiologists and radiologists working together seem to do well with reporting of such extremely important ECF's. CONCLUSIONS: The prevalence of all ECF's was 21.9 %, and 14.9 % of previously unknown ECF's, respectively. However, the prevalence of highly significant ECF's was low. Joint reading with cardiologists and radiologists may increase the number of ECF's detected in CMR studies, but it remains unclear if this could result in an improved long-term outcome of patients undergoing routine CMR.

Cardiovascular magnetic resonance risk stratification in patients with clinically suspected myocarditis.

BACKGROUND: The 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. METHODS: Prospective clinical long-term follow-up of consecutive patients undergoing CMR for work-up of clinically suspected myocarditis at our institution in 2007-2008. RESULTS: Follow-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). CONCLUSION: In 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.

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.

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.

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

BACKGROUND: Exercise 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 RESULTS: We 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). CONCLUSIONS: In 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.

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.