Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: a proof-of-concept pilot study.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease that occurs in previously healthy women. We identified prolactin, mainly its 16-kDa angiostatic and proapoptotic form, as a key factor in PPCM pathophysiology. Previous reports suggest that bromocriptine may have beneficial effects in women with acute onset of PPCM. METHODS AND RESULTS: A prospective, single-center, randomized, open-label, proof-of-concept pilot study of women with newly diagnosed PPCM receiving standard care (PPCM-Std; n=10) versus standard care plus bromocriptine for 8 weeks (PPCM-Br, n=10) was conducted. Because mothers receiving bromocriptine could not breast-feed, the 6-month outcome of their children (n=21) was studied as a secondary end point. Blinded clinical, hemodynamic, and echocardiographic assessments were performed at baseline and 6 months after diagnosis. Cardiac magnetic resonance imaging was performed 4 to 6 weeks after diagnosis in PPCM-Br patients. There were no significant differences in baseline characteristics, including serum 16-kDa prolactin levels and cathepsin D activity, between the 2 study groups. PPCM-Br patients displayed greater recovery of left ventricular ejection fraction (27% to 58%; P=0.012) compared with PPCM-Std patients (27% to 36%) at 6 months. One patient in the PPCM-Br group died compared with 4 patients in the PPCM-Std group. Significantly fewer PPCM-Br patients (n=1, 10%) experienced the composite end point of poor outcome defined as death, New York Heart Association functional class III/IV, or left ventricular ejection fraction <35% at 6 months compared with the PPCM-Std patients (n=8, 80%; P=0.006). Cardiac magnetic resonance imaging revealed no intracavitary thrombi. Infants of mothers in both groups showed normal growth and survival. CONCLUSIONS: In this trial, the addition of bromocriptine to standard heart failure therapy appeared to improve left ventricular ejection fraction and a composite clinical outcome in women with acute severe PPCM, although the number of patients studied was small and the results cannot be considered definitive. Larger-scale multicenter and blinded studies are in progress to test this strategy more robustly.

Review: Contrast-enhanced magnetic resonance in the diagnosis and management of cardiac sarcoidosis.

Sarcoidosis is a relatively rare inflammatory condition which potentially carries high morbidity and substantial mortality. Due to the fact that it does not subject patients to ionizing radiation, has high temporal, spatial and contrast resolutions, cardiovascular magnetic resonance imaging (CMR) has become an important diagnostic and prognostic modality in the evaluation for cardiac involvement in this condition. This review provides relevant clinical and pathophysiological background on cardiac sarcoidosis, whilst detailing the role of CMR imaging in the diagnosis, and management of this condition.

Right ventricular involvement and the extent of left ventricular enhancement with magnetic resonance predict adverse outcome in pulmonary sarcoidosis.

AIMS: Cardiac involvement is the main determinant of poor outcomes in sarcoidosis. Right ventricular (RV) dysfunction and left ventricular (LV) late gadolinium enhancement (LGE) have been reported to be predictive of adverse outcome in non-ischaemic cardiomyopathies. The aim of our study was to determine whether delayed RV LGE with cardiovascular magnetic resonance would be predictive of adverse events in addition to LV LGE during the long-term follow-up of pulmonary sarcoidosis patients. METHODS AND RESULTS: Eighty-four consecutive biopsy-proven pulmonary sarcoidosis patients were followed for a median of 56 months [38-74] after baseline delayed contrast-enhanced cardiac magnetic resonance. The composite primary endpoint consisted of admission for congestive heart failure, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy, pacemaker implantation for high degree atrio-ventricular block, or cardiac death. The composite secondary endpoint included all-cause mortality in addition to the primary endpoint. RV and LV LGE were demonstrated in respectively 12 and 27 patients. Five of 10 events included in the primary endpoint occurred in the group with RV LGE. RV LGE, LV, or biventricular LGE yielded Cox hazard ratios of 8.71 [95% confidence interval (CI) 1.90-23.81], 9.22 (95% CI 1.96-43.45), and 12.09 (95% CI 3.43-42.68) for the composite primary endpoint. In a multivariate model, the predictive value of biventricular LGE for the composite primary and secondary endpoints was strongest. Kaplan-Meier event-free survival curves were most significant for RV LGE and biventricular LGE (log rank with P < 0.001). CONCLUSIONS: Biventricular LGE at presentation is the strongest, independent predictor of adverse outcome during long-term follow-up. Asymptomatic myocardial scar <8% of LV mass carried a favourable long-term outcome.

Right ventricular involvement in cardiac sarcoidosis demonstrated with cardiac magnetic resonance.

AIMS: Cardiac involvement in sarcoidosis is reported in up to 30% of patients. Left ventricular involvement demonstrated by contrast-enhanced cardiac magnetic resonance has been well validated. We sought to determine the prevalence and distribution of right ventricular late gadolinium enhancement in patients diagnosed with pulmonary sarcoidosis. METHODS AND RESULTS: We prospectively evaluated 87 patients diagnosed with pulmonary sarcoidosis with contrast-enhanced cardiac magnetic resonance for right ventricular involvement. Pulmonary artery pressures were non-invasively evaluated with Doppler echocardiography. Patient characteristics were compared between the groups with and without right ventricular involvement, and right ventricular enhancement was correlated with pulmonary hypertension, ventricular mass, volume, and systolic function. Left ventricular late gadolinium enhancement was demonstrated in 30 patients (34%). Fourteen patients (16%) had right ventricular late gadolinium enhancement, with sole right ventricular enhancement in only two patients. The pattern of right ventricular enhancement consisted of right ventricular outflow tract enhancement in 1 patient, free wall enhancement in 8 patients, ventricular insertion point enhancement in 10 patients, and enhancement of the right side of the interventricular septum in 11 patients. Pulmonary arterial hypertension correlated with the presence of right ventricular enhancement (P < 0.001). Right ventricular enhancement correlated with systolic ventricular dysfunction (P < 0.001), hypertrophy (P = 0.001), and dilation (P < 0.001). CONCLUSIONS: Right ventricular enhancement was present in 16% of patients diagnosed with pulmonary sarcoidosis and in 48% of patients with left ventricular enhancement. The presence of right ventricular enhancement correlated with pulmonary arterial hypertension, right ventricular systolic dysfunction, hypertrophy, and dilation.

Contrast-enhanced cardiac Magnetic Resonance: distinction between cardiac sarcoidosis and infarction scar.

Objectives: To review the value of delayed contrast-enhanced cardiac magnetic resonance (CECMR) in differentiating patients with cardiac sarcoidosis (CS) from those with coronary artery disease and recent myocardial infarctions. Background: Late gadolinium enhancement (LGE) accurately delineates myocardial necrosis or fibrosis. The pattern of LGE in ischemic and non-ischemic myocardial disease is different, and might be helpful in distinguishing CS from ischemic disease. Methods: The CECMR studies of 30 patients with CS were compared to those performed in 30 consecutive infarct patients, who had been managed with primary coronary interventions, and 10 healthy controls. Two experienced blinded observers classified patients by assessing the distribution of LGE. Results: LV LGE was present in 29/30 CS (mean 3.8 segments, range 0-12), all infarct (mean 4.3 segments, range 0-9), and none of the patients in the control group. The amount of LV LGE did not differ significantly between CS and infarct patients (19 ± 11% and 19 ± 12%, P= 0.8). The CS group exhibited a predominantly patchy, 3 layer LGE (P = 0.01), whereas confluent transmural LGE (P = 0.04) with a vascular distribution (P < 0.001) was prevalent in the infarct group. Significantly more RV LGE (P = 0.01) and dilation (P = 0.02) were found in the CS group. The two observers classified patients correctly as CS in 72% and 83% of cases, as ischemic in nature in 77% and 80% of cases, and as normal in 90% and 100% respectively. Conclusions: Gadolinium CMR was helpful in differentiating patients with CS from patients with ischemic heart disease and previous myocardial infarctions. In a subgroup of ischemic patients the pattern of LGE was atypical, and suggestive of non-ischemic etiology. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 307-314).

Evaluation of the accuracy of gadolinium-enhanced cardiovascular magnetic resonance in the diagnosis of cardiac sarcoidosis.

OBJECTIVES: This study analyzed the accuracy of gadolinium-enhanced cardiovascular magnetic resonance (CMR) for the diagnosis of cardiac sarcoidosis (CS). BACKGROUND: The diagnosis of CS was made according to the guidelines of the Japanese Ministry of Health and Welfare (1993); CMR has not been incorporated into the guidelines, and the diagnostic accuracy of CMR for the diagnosis of CS has not yet been evaluated. METHODS: We performed an analysis of 12-lead electrocardiograms (ECGs), 24-h ambulatory ECGs, echocardiograms, thallium scintigrams, and gadolinium-enhanced CMR studies in 58 biopsy-proven pulmonary sarcoidosis patients assessed for CS. The diagnostic accuracy of CMR for CS was determined using modified Japanese guidelines as the gold standard. RESULTS: The diagnosis of CS was made in 12 of 58 patients (21%); CMR revealed late gadolinium enhancement (LGE), mostly involving basal and lateral segments (73%), in 19 patients. In 8 of the 19 patients, scintigraphy was normal, while patchy LGE was present. The sensitivity and specificity of CMR were 100% (95% confidence interval, 78% to 100%) and 78% (95% confidence interval, 64% to 89%), and the positive and negative predictive values were 55% and 100%, respectively, with an overall accuracy of 83%. CONCLUSIONS: In patients with sarcoidosis, CMR is a useful diagnostic tool to determine cardiac involvement. New diagnostic guidelines should include CMR.

Cardiac involvement in patients with pulmonary sarcoidosis assessed at two university medical centers in the Netherlands.

STUDY OBJECTIVES: We aimed to determine cardiac involvement in patients with pulmonary sarcoidosis (PS) followed up at two university medical centers in the Netherlands. DESIGN: We reviewed the findings in consecutive patients assessed by our departments during 1998 to 2004, and classified them as patients who had presented with symptoms of cardiac sarcoidosis (CS) [group A], and those who had been screened for this condition (group B). SETTING: Two university medical centers in the Netherlands. PATIENTS: One hundred one patients (69 men [mean age, 47.6 years] and 32 women [mean age, 47.3 years]) with biopsy-proven PS. INTERVENTIONS: Twelve-lead ECG (n = 101), ambulatory ECG (n = 74), echocardiography (n = 80), (201)Tl single-photon emission CT (n = 61), cardiac MRI (n = 87), coronary angiography to exclude coronary artery disease (n = 17), and endomyocardial biopsy (n = 9). MEASUREMENTS: ECG, structural, and functional cardiac abnormalities according to the modified guidelines of the Japanese Ministry of Health and Welfare (1993). RESULTS: Sixteen of 19 patients in group A and 3 of 82 patients in group B received a diagnosis of CS. During a mean follow-up of 1.7 years (range, 3 months to 4 years), four patients in group A died (20%) and nine patients received a pacemaker and/or an implantable cardioverter-defibrillator (47%), while the patients in group B had an uncomplicated course. CONCLUSIONS: Once symptomatic CS develops in PS patients, the prognosis becomes very grim. In contrast, the prognosis in asymptomatic cardiac involvement in PS patients is good. Considering the poor prognosis of symptomatic CS, pulmonologists should consider regular screening of their PS patients for cardiac involvement with straightforward detection methods.

The additional value of gadolinium-enhanced MRI to standard assessment for cardiac involvement in patients with pulmonary sarcoidosis.

AIM: To determine whether gadolinium-enhanced cardiac MRI (CMR) was of additional diagnostic value to standard assessment in patients with sarcoidosis who underwent evaluation for cardiac involvement. METHODS: We reviewed the findings in patients with pulmonary sarcoidosis who had been assessed with ECG, Doppler echocardiography, 201Tl scintigraphy, and CMR from 2002 to 2004. RESULTS: Of the 55 evaluated patients, standard evaluation diagnosed cardiac involvement in 13 patients while CMR diagnosed myocardial scarring (mean +/- SD, 2.5 +/- 1.9 segments) [all 6 patients] and impaired systolic left ventricular function (1 patient) in an additional 6 patients. The extent of delayed enhancement correlated with disease duration (p < 0.05), ventricular dimensions and function (p < 0.001), severity of mitral regurgitation (p < 0.05), and the presence of ventricular tachycardias (p < 0.001). Patients in whom cardiac involvement was diagnosed only with CMR had less myocardial scarring and functional impairment (p < 0.05) compared to patients with a diagnosis made by standard assessment. CONCLUSION: CMR provides an accurate estimation of the extent of cardiac involvement and may reveal signs of early infiltration that are not detected by standard assessment. The extent of late enhancement with gadolinium relates to the severity of cardiac involvement and may therefore have prognostic implications.

Aneurysm of the left aortic sinus causing acute myocardial infarction.

This report describes the findings and management of a young male who presented with an acute ST-segment elevation myocardial infarction due to compression of the circumflex coronary artery by a large aneurysm of left sinus of Valsalva.

Cardiac sarcoidosis evaluated with gadolinium-enhanced magnetic resonance and contrast-enhanced 64-slice computed tomography.

Sarcoidosis is a multi-system granulomatous disorder of unknown etiology with symptomatic cardiac involvement in up to 7% of patients. The clinical features of sarcoid heart disease include congestive heart failure, arrhythmias, conduction disturbances, and sudden death. We evaluated the value of contrast-enhanced multi-detector computed tomography in delineating myocardial scar and granulomatous inflammation by comparing our findings with gadolinium magnetic resonance in a patient diagnosed with cardiac sarcoidosis.