Ferumoxytol-enhanced cardiovascular magnetic resonance detection of early stage acute myocarditis.

BACKGROUND: The diagnostic utility of cardiovascular magnetic resonance (CMR) is limited during the early stages of myocarditis. This study examined whether ferumoxytol-enhanced CMR (FE-CMR) could detect an earlier stage of acute myocarditis compared to gadolinium-enhanced CMR. METHODS: Lewis rats were induced to develop autoimmune myocarditis. CMR (3 T, GE Signa) was performed at the early- (day 14, n = 7) and the peak-phase (day 21, n = 8) of myocardial inflammation. FE-CMR was evaluated as % myocardial dephasing signal loss on gradient echo images at 6 and 24 h (6 h- & 24 h-FE-CMR) following the administration of ferumoxytol (300µmolFe/kg). Pre- and post-contrast T2* mapping was also performed. Early (EGE) and late (LGE) gadolinium enhancement was obtained after the administration of gadolinium-DTPA (0.5 mmol/kg) on day 14 and 21. Healthy rats were used as control (n = 6). RESULTS: Left ventricular ejection fraction (LVEF) was preserved at day 14 with inflammatory cells but no fibrosis seen on histology. EGE and LGE at day 14 both showed limited myocardial enhancement (EGE: 11.7 ± 15.5%; LGE: 8.7 ± 8.7%; both p = ns vs. controls). In contrast, 6 h-FE-CMR detected extensive myocardial signal loss (33.2 ± 15.0%, p = 0.02 vs. EGE and p < 0.01 vs. LGE). At day 21, LVEF became significantly decreased (47.4 ± 16.4% vs control: 66.2 ± 6.1%, p < 0.01) with now extensive myocardial involvement detected on EGE, LGE, and 6 h-FE-CMR (41.6 ± 18.2% of LV). T2* mapping also detected myocardial uptake of ferumoxytol both at day 14 (6 h R2* = 299 ± 112 s- 1vs control: 125 ± 26 s- 1, p < 0.01) and day 21 (564 ± 562 s- 1, p < 0.01 vs control). Notably, the myocardium at peak-phase myocarditis also showed significantly higher pre-contrast T2* (27 ± 5 ms vs control: 16 ± 1 ms, p < 0.001), and the extent of myocardial necrosis had a strong positive correlation with T2* (r = 0.86, p < 0.001). CONCLUSIONS: FE-CMR acquired at 6 h enhance detection of early stages of myocarditis before development of necrosis or fibrosis, which could potentially enable appropriate therapeutic intervention.

Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging.

PURPOSE: HCM is the most common inherited cardiomyopathy. Historically, there has been poor correlation between genotype and phenotype. However, CMR has the potential to more accurately assess disease phenotype. We characterized phenotype with CMR in a cohort of patients with confirmed HCM and high prevalence of genetic testing. METHODS: Patients with a diagnosis of HCM, who had undergone contrast-enhanced CMR were identified. Left ventricular mass index (LVMI) and volumes were measured from steady-state free precession sequences. Late gadolinium enhancement (LGE) was quantified using the full width, half maximum method. All patients were prospectively followed for the development of septal reduction therapy, arrhythmia or death. RESULTS: We included 273 patients, mean age 51.2 ± 15.5, 62.9% male. Of those patients 202 (74.0%) underwent genetic testing with 90 pathogenic, likely pathogenic, or rare variants and 13 variants of uncertain significance identified. Median follow-up was 1138 days. Mean LVMI was 82.7 ± 30.6 and 145 patients had late gadolinium enhancement (LGE). Patients with beta-myosin heavy chain (MYH7) mutations had higher LV ejection fraction (68.8 vs 59.1, p<0.001) than those with cardiac myosin binding protein C (MYBPC3) mutations. Patients with MYBPC3 mutations were more likely to have LVEF < 55% (29.7% vs 4.9%, p = 0.005) or receive a defibrillator than those with MYH7 mutations (54.1% vs 26.8%, p = 0.020). CONCLUSIONS: We found that patients with MYBPC3 mutations were more likely to have impaired ventricular function and may be more prone to arrhythmic events. Larger studies using CMR phenotyping may be capable of identifying additional characteristics associated with less frequent genetic causes of HCM.

Myocardial viability of the peri-infarct region measured by T1 mapping post manganese-enhanced MRI correlates with LV dysfunction.

BACKGROUND: Manganese-enhanced MRI (MEMRI) detects viable cardiomyocytes based on the intracellular manganese uptake via L-type calcium-channels. This study aimed to quantify myocardial viability based on manganese uptake by viable myocardium in the infarct core (IC), peri-infarct region (PIR) and remote myocardium (RM) using T1 mapping before and after MEMRI and assess their association with cardiac function and arrhythmogenesis. METHODS: Fifteen female swine had a 60-minute balloon ischemia-reperfusion injury in the LAD. MRI (Signa 3T, GE Healthcare) and electrophysiological study (EPS) were performed 4 weeks later. MEMRI and delayed gadolinium-enhanced MRI (DEMRI) were acquired on LV short axis. The DEMRI positive total infarct area was subdivided into the regions of MEMRI-negative non-viable IC and MEMRI-positive viable PIR. T1 mapping was performed to evaluate native T1, post-MEMRI T1, and delta R1 (R1post-R1pre, where R1 equals 1/T1) of each territory. Their correlation with LV function and EPS data was assessed. RESULTS: PIR was characterized by intermediate native T1 (1530.5 ±â€¯75.2 ms) compared to IC (1634.7 ±â€¯88.4 ms, p = 0.001) and RM (1406.4 ±â€¯37.9 ms, p < 0.0001). Lower post-MEMRI T1 of PIR (1136.3 ±â€¯99.6 ms) than IC (1262.6 ±â€¯126.8 ms, p = 0.005) and higher delta R1 (0.23 ±â€¯0.08 s-1) of PIR than IC (0.18 ±â€¯0.09 s-1, p = 0.04) indicated higher myocardial manganese uptake of PIR compared to IC. Post-MEMRI T1 (r = -0.57, p = 0.02) and delta R1 (r = 0.51, p = 0.04) of PIR correlated significantly with LVEF. CONCLUSIONS: PIR is characterized by higher manganese uptake compared to the infarct core. In the subacute phase post-IR, PIR viability measured by post-MEMRI T1 correlates with cardiac function.

Inappropriate ICD shock due to hot tub-induced external electrical interference.

BACKGROUND: A 72-year-old white male with a history of rapid nonsustained ventricular tachycardia, hypertrophic cardiomyopathy, and intermittent Brugada-type ECG had a single-lead implantable cardioverter-defibrillator (ICD) implantation and received a sudden ICD shock while in the hot tub. To the best of our knowledge this is the first case report of hot tub jet-induced inappropriate ICD shock. METHODS: ICD interrogation and analysis of intracardiac electrograms and event markers. RESULTS: ICD interrogation revealed inappropriate ICD shocks due to electrical interference of hot tub engine; 60-cycle electrical artifact mimicking fast ventricular fibrillation erroneously detected by the device. The device then delivered a 34.8 joules shock while the patient was actually in sinus rhythm. CONCLUSIONS: Electrical interference due to external sources such as hot tub engines may occur and produce an inappropriate detection and ICD shock. Precaution and patient education is warranted.

Ranolazine: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias.

Ranolazine is currently approved as an antianginal agent in patients with chronic angina (class IIA). Ranolazine exhibits antiarrhythmic effects that are related to its multichannel blocking effect, predominantly inhibition of late sodium (late INa) current and the rapid potassium rectifier current (IKr), as well as ICa, late ICa, and INa-Ca. It also suppresses the early and delayed after depolarizations. Ranolazine is effective in the suppression of atrial and ventricular arrhythmias (off-label use) without significant proarrhythmic effect. Currently, ongoing trials are evaluating the efficacy and safety of ranolazine in patients with cardiac arrhythmias; preliminary results suggest that ranolazine, when used alone or in combination with dronedarone, is safe and effective in reducing atrial fibrillation. Ranolazine is not currently approved by the US Food and Drug Administration as an antiarrhythmic agent.

Relationship between echocardiographic and magnetic resonance derived measures of right ventricular size and function in patients with pulmonary hypertension.

BACKGROUND: Transthoracic echocardiographic (TTE) imaging is the mainstay of clinical practice for evaluating right ventricular (RV) size and function, but its accuracy in patients with pulmonary hypertension has not been well validated. METHODS: Magnetic resonance imaging (MRI) and TTE images were retrospectively reviewed in 40 consecutive patients with pulmonary hypertension. RV and left ventricular volumes and ejection fractions were calculated using MRI. TTE areas and indices of RV ejection fraction (RVEF) were compared. RESULTS: The average age was 42 ± 12 years, with a majority of women (85%). There was a wide range of mean pulmonary arterial pressures (27-81 mm Hg) and RV end-diastolic volumes (111-576 mL), RVEFs (8%-67 %), and left ventricular ejection fractions (26%-72%) by MRI. There was a strong association between TTE and MRI-derived parameters: RV end-diastolic area (by TTE imaging) and RV end-diastolic volume (by MRI), R(2) = 0.78 (P < .001); RV fractional area change by TTE imaging and RVEF by MRI, R(2) = 0.76 (P < .001); and tricuspid annular plane systolic excursion by TTE imaging and RVEF by MRI, R(2) = 0.64 (P < .001). By receiver operating characteristic curve analysis, an RV fractional area change < 25% provided excellent discrimination of moderate systolic dysfunction (RVEF < 35%), with an area under the curve of 0.97 (P < .001). An RV end-diastolic area index of 18 cm(2)/m(2) provided excellent discrimination for moderate RV enlargement (area under the curve, 0.89; P < .001). CONCLUSIONS: Echocardiographic estimates of RV volume (by RV end-diastolic area) and function (by RV fractional area change and tricuspid annular plane systolic excursion) offer good approximations of RV size and function in patients with pulmonary hypertension and allow the accurate discrimination of normal from abnormal.

Quantitative tissue characterization of infarct core and border zone in patients with ischemic cardiomyopathy by magnetic resonance is associated with future cardiovascular events.

OBJECTIVES: This study evaluates how characterization of tissue heterogeneity of myocardial infarction by cardiovascular magnetic resonance (CMR) is associated with cardiovascular events (CVE) in patients with ischemic cardiomyopathy (ICM). BACKGROUND: Prior studies demonstrated that the quantification of myocardial scar volume by CMR is superior to left ventricular end-diastolic volume, left ventricular end-systolic volume, and left ventricular ejection fraction (LVEF) in predicting future CVE in ICM patients. Evaluation of infarct heterogeneity by measuring infarct core and border zones through CMR might have a higher association with CVE. METHODS: Seventy patients (mean LVEF: 25 +/- 11%) considered for revascularization or medical management +/- implantable cardiac defibrillator were enrolled. A 1.5-T GE MRI (Signa, GE Healthcare, Milwaukee, Wisconsin) was used to acquire cine and delayed enhancement images. The patients' core and border zones of infarcted myocardium were analyzed and followed for CVE. RESULTS: Larger infarct border zone and its percentage of myocardium were found in the 29 patients (41%) who had CVE (median 13.3 g [interquartile range (IQR) 8.4 to 25.1 g] vs. 8.0 g [IQR 3.0 to 14.5 g], p = 0.02 and 7.8% [IQR 4.9% to 17.0%] vs. 4.1% [IQR 1.9% to 9.3%], p = 0.02, respectively). The core infarct zone and its percentage of myocardium, left ventricular end-diastolic volume, left ventricular end-systolic volume, and LVEF were not statistically significant. Sub-analysis of the medical management and revascularization patients with CVE demonstrated that the medically managed patients had a larger border zone, whereas there was no difference between border and core zones in the revascularization group (p < 0.05). CONCLUSIONS: Quantification of core and border zones and their percentages of myocardium through CMR is associated with future CVE and might assist in the management of patients with ICM.

Quantitative characterization of myocardial infarction by cardiovascular magnetic resonance predicts future cardiovascular events in patients with ischemic cardiomyopathy.

BACKGROUND: Cardiovascular magnetic resonance (CMR) can provide quantitative data of the myocardial tissue utilizing high spatial and temporal resolution along with exquisite tissue contrast. Previous studies have correlated myocardial scar tissue with the occurrence of ventricular arrhythmia. This study was conducted to evaluate whether characterization of myocardial infarction by CMR can predict cardiovascular events in patients with ischemic cardiomyopathy (ICM). RESULTS: We consecutively studied 86 patients with ICM (LVEF < 50%, mean LVEF: 26 +/- 12%) with CMR before revascularization or medication therapy +/- implantable cardiac defibrillator, determined the amount of myocardial scar, and followed for development of cardiovascular events. Thirty-three patients (38%) had cardiovascular events (mean follow-up: 20 +/- 16 months). Patients who developed cardiovascular events had larger scar volume and scar percentage of the myocardium than those who did not develop cardiovascular events (16.8 +/- 12.4 cm3 vs. 11.7 +/- 12.6 cm3, p = 0.023 and 10.2 +/- 6.9% vs. 7.2 +/- 6.7%, p = 0.037, respectively). There were no significant differences in LVEDV, LVESV and LVEF between the patients with and without cardiovascular events (231 +/- 76 ml vs. 230 +/- 88 ml; 180 +/- 73 ml vs. 175 +/- 90 ml; and 25 +/- 10% vs. 27 +/- 13%, respectively). CONCLUSION: Quantification of the scar volume and scar percentage by CMR is superior to LVEDV, LVESV, and LVEF in prognosticating the future likelihood of the development of cardiovascular events in patients with ICM.

Safety of exercise testing in the chest pain unit: 31-mm ST elevation in variant angina.

We discuss a patient who presented with symptoms classic for variant angina with dramatic 31-mm ST elevation secondary to exercise testing in the chest pain unit, in whom neither myocardial infarction nor severe arrhythmia resulted. Although exercise testing is deemed generally safe, it has not been studied for safety per se in patients with variant angina. Further studies are needed to determine if the magnitude of ST elevation during exercise testing carries prognostic significance.