ECG findings in comparison to cardiovascular MR imaging in viral myocarditis.

OBJECTIVES: We sought (1) to assess prevalence and type of ECG abnormalities in patients with biopsy proven myocarditis and signs of myocardial damage indicated by LGE, and (2) to evaluate whether ECG abnormalities are related to the pattern of myocardial damage. BACKGROUND: Prevalence and type of ECG abnormalities in patients presenting biopsy proven myocarditis, as well as any relation between ECG abnormalities and the in vivo pattern of myocardial damage are unknown. METHODS: Eighty-four consecutive patients fulfilled the following criteria: (1) newly diagnosed biopsy proven viral myocarditis, and (2) non-ischemic LGE, and (3) standard 12-lead-ECG upon admission. RESULTS: Sixty-five patients with biopsy proven myocarditis had abnormal ECGs upon admission (77%). In this group, ST-abnormalities were detected most frequently (69%), followed by bundle-branch-block in 26%, and Q-waves in 8%. Atrial fibrillation was present in 6%, and AV-Block in two patients. In patients with septal LGE ST-abnormalities were more frequently located in anterolateral leads compared to patients with lateral LGE, in whom ST-abnormalities were most frequently observed in inferolateral leads. Bundle-branch-block occurred more often in patients with septal LGE (11/17). Four of five patients with Q-waves had severe and almost transmural LGE in the lateral wall. CONCLUSION: ECG abnormalities can be found in most patients with biopsy proven viral myocarditis at initial presentation. However, similar to suspected acute myocardial infarction, a normal ECG does not rule out myocarditis. ECG findings are related to the amount and area of damage as indicated by LGE, which confirms the important clinical role of 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.

Usefulness of pericardial effusion as new diagnostic criterion for noninvasive detection of myocarditis.

Cardiovascular magnetic resonance (CMR) imaging holds promise for diagnosing myocarditis in vivo. The CMR diagnosis of myocarditis is determined by the ventricular morphology/function, late gadolinium enhancement, and T(2)-weighted imaging for myocardial edema. However, in routine clinical practice, we encounter patients with suspected myocarditis in the absence of left ventricular dysfunction, myocardial edema, or late gadolinium enhancement. In the present study, we sought to determine whether the presence of pericardial effusion could serve as a new diagnostic criterion and improve the sensitivity of CMR imaging to detect myocarditis. A total of 35 consecutive patients with biopsy proven virus-associated myocarditis, onset of clinical symptoms within the past 3 months, and normal left ventricular function were enrolled in the present study. All patients underwent echocardiography, CMR imaging, and endomyocardial biopsy for workup of myocarditis. Late gadolinium enhancement was present in 16 patients (46%). Myocardial edema on T(2)-weighted imaging was present in 4 patients, but in just 1, it was the only abnormal finding. Pericardial effusion was present in 14 patients (40%). In 7 patients with myocarditis (20%), pericardial effusion was the only abnormal finding. Pericardial effusion, used as an additional diagnostic criterion, improved the sensitivity of CMR imaging for myocarditis from 46% to 66% (p = 0.023). In conclusion, pericardial effusion detected by CMR imaging might serve as a new diagnostic criterion for the noninvasive diagnosis of myocarditis in patients with recent onset of clinical symptoms and normal left ventricular function.

Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy.

OBJECTIVES: We sought to establish the prognostic value of a comprehensive cardiovascular magnetic resonance (CMR) examination in risk stratification of hypertrophic cardiomyopathy (HCM) patients. BACKGROUND: With annual mortality rates ranging between 1% and 5%, depending on patient selection, a small but significant number of HCM patients are at risk for an adverse event. Therefore, the identification of and prophylactic therapy (i.e., defibrillator placement) in patients with HCM who are at risk of dying are imperative. METHODS: Two-hundred forty-three consecutive patients with HCM were prospectively enrolled. All patients underwent initial CMR, and 220 were available for clinical follow-up. The mean follow-up time was 1,090 days after CMR. End points were all-cause and cardiac mortality. RESULTS: During follow-up 20 of the 220 patients died, and 2 patients survived sudden cardiac death due to adequate implantable cardioverter-defibrillator discharge. Most events (n = 16) occurred for cardiac reasons; the remaining 6 events were related to cancer and accidents. Our data indicate that the presence of scar visualized by CMR yields an odds ratio of 5.47 for all-cause mortality and of 8.01 for cardiac mortality. This might be superior to classic clinical risk factors, because in our dataset the presence of 2 risk factors yields an odds ratio of 3.86 for all-cause and of 2.20 for cardiac mortality, respectively. Multivariable analysis also revealed the presence of late gadolinium enhancement as a good independent predictor of death in HCM patients. CONCLUSIONS: Among our population of largely low or asymptomatic HCM patients, the presence of scar indicated by CMR is a good independent predictor of all-cause and cardiac mortality.

Diagnostic value of perfusion cardiovascular magnetic resonance in patients with angina pectoris but normal coronary angiograms assessed by intracoronary acetylcholine testing.

BACKGROUND: Perfusion cardiovascular magnetic resonance (CMR) has a high sensitivity for the detection of significant coronary artery disease (CAD). However, the specificity of this method is lower than its sensitivity. The reason for this observation is hitherto unclear and has been either explained by 'false-positive' results or by microvascular dysfunction in patients without CAD. OBJECTIVE: To evaluate whether pathological myocardial perfusion-CMR imaging in symptomatic patients without significant CAD is associated with coronary epicardial or microvascular dysfunction. METHODS: In this retrospective study, 42 patients who presented with unstable angina pectoris underwent (a) an adenosine-stress perfusion-CMR study; (b) coronary angiography; (c) intracoronary acetylcholine (ACh) testing following coronary angiography with exclusion of significant CAD. The CMR protocol comprised cine imaging followed by adenosine first-pass perfusion imaging and late gadolinium enhancement-CMR. Diagnostic left ventriculography and multiplane coronary angiography were performed before intracoronary ACh testing. RESULTS: An adenosine-induced, reversible subendocardial perfusion defect was detected in 22/42 patients (52%) without significant CAD. Coronary epicardial vasospasm was detected in 10/42 patients (24%) while microvascular dysfunction was found in 20/42 patients (48%). Patients with a reversible stress-induced perfusion defect had significantly more often a pathological coronary epicardial or microvascular vasoreaction (20/22; 91%) during intracoronary ACh testing than those without a perfusion defect (10/20; 50%; p<0.01). Univariate correlation analyses revealed a substantial association between a pathological ACh-testing result and a perfusion defect in the antecedent CMR study (r= +0.45; p<0.01). CONCLUSIONS: Reversible perfusion defects depicted by perfusion-CMR in patients without significant CAD are mostly due to coronary epicardial or microvascular dysfunction, and correct interpretation of such perfusion-CMR results may enable targeted treatment.

Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis: noninvasive imaging compared to endomyocardial biopsy.

OBJECTIVES: We sought to evaluate the diagnostic performance of cardiovascular magnetic resonance imaging (CMRI) for detection of cardiac amyloidosis compared with endomyocardial biopsy (EMB) in a clinical routine setting. BACKGROUND: For the clinical workup of heart failure with restrictive filling, pattern cardiac amyloidosis is an important differential diagnosis that is difficult to verify with current noninvasive techniques, especially in the presence of myocardial hypertrophy. METHODS: A total of 33 consecutive patients underwent both CMRI and EMB for workup of heart failure with restrictive filling pattern in combination with myocardial hypertrophy (n = 24) and/or clinical conditions often associated with cardiac amyloidosis (n = 18). RESULTS: Cardiac amyloidosis was detected by EMB in 15 of the 33 patients. In patients with biopsy-proven cardiac amyloidosis, CMRI revealed a distinct pattern of late gadolinium enhancement, which was distributed over the entire subendocardial circumference, extending in various degrees into the neighboring myocardium. This pattern was found in 12 of the 15 patients diagnosed with cardiac amyloidosis by EMB, compared with only 1 individual in the group of 18 patients diagnosed with other myocardial diseases. Consequently, using this pattern as a diagnostic criterion, the sensitivity of CMRI for diagnosing cardiac amyloidosis was 80%, yielding a specificity of 94%. The positive predictive value was 92%, and the negative predictive value was 85%. CONCLUSIONS: In patients with biopsy-proven cardiac amyloidosis, late gadolinium enhancement frequently occurs in a peculiar pattern. On the basis of the gold standard, EMB, noninvasive CMRI can be used to diagnose or rule out cardiac amyloidosis with good sensitivity and excellent specificity in a clinical routine setting.

Value of cardiovascular magnetic resonance stress perfusion testing for the detection of coronary artery disease in women.

OBJECTIVES: We wanted to assess the value of cardiovascular magnetic resonance (CMR) stress testing for evaluation of women with suspected coronary artery disease (CAD). BACKGROUND: A combined perfusion and infarction CMR examination can accurately diagnose CAD in the clinical setting in a mixed gender population. METHODS: We prospectively enrolled 147 consecutive women with chest pain or other symptoms suggestive of CAD at 2 centers (Duke University Medical Center, Robert-Bosch-Krankenhaus). Each patient underwent a comprehensive clinical evaluation, a CMR stress test consisting of cine rest function, adenosine-stress and rest perfusion, and delayed-enhancement CMR infarction imaging, and X-ray coronary angiography within 24 h. The components of the CMR test were analyzed visually both in isolation and combined using a pre-specified algorithm. Coronary artery disease was defined as stenosis > or =70% on quantitative analysis of coronary angiography. RESULTS: Cardiovascular magnetic resonance imaging was completed in 136 females (63.0 +/- 11.1 years), 37 (27%) women had CAD on coronary angiography. The combined CMR stress test had a sensitivity, specificity, and accuracy of 84%, 88%, and 87%, respectively, for the diagnosis of CAD. Diagnostic accuracy was high at both sites (Duke University Medical Center 82%, Robert-Bosch-Krankenhaus 90%; p = 0.18). The accuracy for the detection of CAD was reduced when intermediate grade stenoses were included (82% vs. 87%; p = 0.01 compared the cutoff of stenosis > or =50% vs. > or =70%). The sensitivity was lower in women with single-vessel disease (71% vs. 100%; p = 0.06 compared with multivessel disease) and small left ventricular mass (69% vs. 95%; p = 0.04 for left ventricular mass < or =97 g vs. >97 g). The latter difference was even more significant after accounting for end-diastolic volumes (70% vs. 100%; p = 0.02 for left ventricular mass indexed to end-diastolic volume < or =1.15 g/ml vs. >1.15 g/ml). CONCLUSIONS: A multicomponent CMR stress test can accurately diagnose CAD in women. Detection of CAD in women with intermediate grade stenosis, single-vessel disease, and with small hearts is challenging.

Presentation, patterns of myocardial damage, and clinical course of viral myocarditis.

BACKGROUND: Enteroviruses and adenoviruses have been considered the most common causes of viral myocarditis, but parvovirus B19 (PVB19) and human herpesvirus 6 (HHV6) are increasingly found in endomyocardial biopsy samples. METHODS AND RESULTS: Consequently, our aim was to evaluate the prevalence and clinical presentation of cardiac PVB19 and/or HHV6 infection in a cohort of myocarditis patients and to follow its clinical course. In addition, we sought to demonstrate patterns of myocardial damage and to determine predictors for chronic heart failure. Our study design consisted of a cardiovascular magnetic resonance protocol as well as endomyocardial biopsies in the myocardial region affected as indicated by cardiovascular magnetic resonance. One hundred twenty-eight patients were enrolled by clinical criteria. In the group of myocarditis patients (n=87), PVB19 (n=49), HHV6 (n=16), and combined PVB19/HHV6 infections (n=15) were detected most frequently. The remaining patients were diagnosed with healing myocarditis (n=15) or did not have myocarditis (n=26). Patients with PVB19 presented in a manner similar to that of myocardial infarction; most had typical subepicardial late gadolinium enhancement in the lateral wall and recovered within months. Conversely, patients with HHV6 and especially with HHV6/PVB19 myocarditis presented with new onset of heart failure, had septal late gadolinium enhancement, and frequently progressed toward chronic heart failure. CONCLUSIONS: Our data indicate that PVB19 and HHV6 are the most important causes for viral myocarditis in Germany and that the clinical presentation is related to the type of virus. Furthermore, clinical presentation, type of virus, and pattern of myocardial damage are related to the clinical course.