Cardiac magnetic resonance in histologically proven eosinophilic myocarditis.

BACKGROUND: Eosinophilic myocarditis (EM) is a life-threatening acute heart disease. Cardiac magnetic resonance (CMR) excels in the assessment of myocardial diseases but CMR studies of EM are limited. We aimed to describe CMR findings in histologically proven EM. METHODS: Patients with histologically proven EM seen at an academic center from 2000 through 2020 were identified. Of the 28 patients ascertained, 15 had undergone CMR for diagnosis and constitute our study cohort. RESULTS: The patients, aged 51 ± 17 years, presented with fever (53%), dyspnea (47%), chest pain (53%), heart block (20%), and blood eosinophilia (60%). On CMR, all 15 patients had myocardial edema with 10 of them (67%) having abnormally high left ventricular (LV) mass as well. LV ejection fraction measured < 50% in 11 patients (73%) and < 30% in 2 (13%), but only 6 (40%) had dilated LV size. Eight patients (53%) had pericardial effusion. LV late gadolinium enhancement (LGE) was found in all but one patient (13/14; 93%). LGE was always multifocal and subendocardial but could involve any myocardial layer. Patients with necrotizing EM by histopathology (n = 6) had higher LGE mass (32.1 ± 16.6% vs 14.5 ± 7.7%, p = 0.050) and more LV segments with LGE (15 ± 2 vs 9 ± 3 out of 17, p = 0.003) than patients (n = 9) without myocyte necrosis. Two patients had LV thrombosis accompanying widespread subendocardial LGE. CONCLUSIONS: In EM, CMR shows myocardial edema and LGE that is typically subendocardial but can involve any myocardial layer. The left ventricle is often non-dilated with moderate-to-severe systolic dysfunction. Pericardial effusion is common. Necrotizing EM presents with extensive myocardial LGE on CMR.

Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis.

Cardiac sarcoidosis (CS) results from epithelioid cell granulomas infiltrating the myocardium and predisposing to conduction disturbances, ventricular tachyarrhythmias, and heart failure. Manifest CS, however, constitutes only the top of an iceberg as advanced imaging uncovers cardiac involvement 4 to 5 times more commonly than what is clinically detectable. Definite diagnosis of CS requires myocardial biopsy and histopathology, but a sufficient diagnostic likelihood can be achieved by combining extracardiac histology of sarcoidosis with clinical manifestations and findings on cardiac imaging. CS can appear as the first or only organ manifestation of sarcoidosis or on top of pre-existing extracardiac disease. Due to the lack of controlled trials, the care of CS is based on observational evidence of low quality. Currently, the treatment involves corticosteroid-based, tiered immunosuppression to control myocardial inflammation with medical and device-based therapy for symptomatic atrioventricular block, ventricular tachyarrhythmias, and heart failure. Recent outcome data indicate 90% to 96% 5-year survival in manifest CS with the 10-year figures ranging from 80% to 90%. Major progress in the care of CS awaits the key to its molecular-genetic pathogenesis and large-scale controlled clinical trials.

Cardiac magnetic resonance in giant cell myocarditis: a matched comparison with cardiac sarcoidosis.

AIMS: Giant cell myocarditis (GCM) is an inflammatory cardiomyopathy akin to cardiac sarcoidosis (CS). We decided to study the findings of GCM on cardiac magnetic resonance (CMR) imaging and to compare GCM with CS. METHODS AND RESULTS: CMR studies of 18 GCM patients were analyzed and compared with 18 CS controls matched for age, sex, left ventricular (LV) ejection fraction and presenting cardiac manifestations. The analysts were blinded to clinical data. On admission, the duration of symptoms (median) was 0.2 months in GCM vs. 2.4 months in CS (P = 0.002), cardiac troponin T was elevated (>50 ng/L) in 16/17 patients with GCM and in 2/16 with CS (P < 0.001), their respective median plasma B-type natriuretic propeptides measuring 4488 ng/L and 1223 ng/L (P = 0.011). On CMR imaging, LV diastolic volume was smaller in GCM (177 ± 32 mL vs. 211 ± 58 mL, P = 0.014) without other volumetric or wall thickness measurements differing between the groups. Every GCM patient had multifocal late gadolinium enhancement (LGE) in a distribution indistinguishable from CS both longitudinally, circumferentially, and radially across the LV segments. LGE mass averaged 17.4 ± 6.3% of LV mass in GCM vs 25.0 ± 13.4% in CS (P = 0.037). Involvement of insertion points extending across the septum into the right ventricular wall, the "hook sign" of CS, was present in 53% of GCM and 50% of CS. CONCLUSION: In GCM, CMR findings are qualitatively indistinguishable from CS despite myocardial inflammation being clinically more acute and injurious. When matched for LV dysfunction and presenting features, LV size and LGE mass are smaller in GCM.

MRI-derived cardiac washout is slowed in the left ventricle and associated with left ventricular non-compaction in young patients with cryptogenic ischemic stroke.

To elucidate underlying disease mechanisms, we compared transition of gadolinium-based contrast agent bolus in cardiac chambers in magnetic resonance imaging between young patents with cryptogenic ischemic stroke and stroke-free controls. We included 30 patients aged 18-50 years with cryptogenic ischemic stroke from the prospective Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers and Outcome (NCT01934725) study and 30 age- and gender-matched stroke-free controls. Dynamic contrast-enhanced T1-weighted first-pass perfusion images were acquired at 1.5 T and analyzed for transit time variables, area under curves, relative blood flow, and maximum and minimum enhancement rates in left atrial appendage, left atrium, and left ventricle. These data were compared with previously published left ventricular non-compaction data of the same study population. Arrival time of contrast agent bolus in superior vena cava was similar in patients and controls (6.7[2.0] vs. 7.1[2.5] cardiac cycles, P = 0.626). Arrival and peak times showed comparable characteristics in patients and controls (P > 0.535). The minimum enhancement rate of the left ventricle was lower in patients than in controls (- 28 ± 11 vs. - 36 ± 13 1/(cardiac cycle), P = 0.012). Area under curves, relative blood flow, and other enhancement rates showed no significant differences between patients and controls (P > 0.107). Relative blood flow of cardiac chambers correlated with non-compacted left ventricular volume ratio (P < 0.011). Our results indicate slower washout of contrast agent and blood flow stagnation in the left ventricle of young patients with cryptogenic ischemic stroke. The washout was associated with left ventricular non-compaction, suggesting conditions favoring formation of intraventricular thrombosis.

Incidence and Predictors of Atrial Fibrillation in Cardiac Sarcoidosis: A Multimodality Imaging Study.

BACKGROUND: In cardiac sarcoidosis (CS), the risk and predictors of new-onset atrial fibrillation (AF) are poorly known. OBJECTIVES: The authors evaluated the incidence and characteristics of AF in newly diagnosed CS. METHODS: The authors studied 118 patients (78 women, mean age 50 years) with AF-naive CS having undergone cardiac 18F-fluorodexoyglucose positron emission tomography (18F-FDG PET) at the time of diagnosis. Details of patient characteristics and medical or device therapy were collected from hospital charts. The PET scans were re-analyzed for presence of atrial and ventricular inflammation, and coincident cardiac magnetic resonance (CMR) studies and single-photon emission computed tomography (SPECT) perfusions were analyzed for cardiac structure and function, including the presence and extent of myocardial scarring. Detection of AF was based on interrogation of intracardiac devices and on ambulatory or 12-lead electrocardiograms. RESULTS: Altogether 34 patients (29%) suffered paroxysms of AF during follow-up (median, 3 years) with persistent AF developing in 7 patients and permanent AF in 4. The estimated 5-year incidence of AF was 55% (95% CI: 34%-72%) in the 39 patients with atrial 18F-FDG uptake at the time of diagnosis vs 18% (95% CI: 10%-28%) in the 79 patients without atrial uptake (P < 0.001). In cause-specific Cox regression analysis, atrial uptake was an independent predictor of AF (P < 0.001) with HR of 6.01 (95% CI: 2.64-13.66). Other independent predictors were an increased left atrial maximum volume (P < 0.01) and history of sleep apnea (P < 0.01). Ventricular involvement by PET, SPECT, or CMR was nonpredictive. Symptoms of AF prompted electrical cardioversion in 12 patients (35%). Three of the 34 patients (9%) experiencing AF suffered a stroke versus none of those remaining free of AF. CONCLUSIONS: In newly diagnosed CS, future AF is relatively common and associated with atrial inflammation and enlargement on multimodality cardiac imaging.

Incidence of Sudden Cardiac Death and Life-Threatening Arrhythmias in Clinically Manifest Cardiac Sarcoidosis With and Without Current Indications for an Implantable Cardioverter Defibrillator.

BACKGROUND: Cardiac sarcoidosis (CS) predisposes to sudden cardiac death (SCD). Guidelines for implantable cardioverter defibrillators (ICDs) in CS have been issued by the Heart Rhythm Society in 2014 and the American College of Cardiology/American Heart Association/Heart Rhythm Society consortium in 2017. How well they discriminate high from low risk remains unknown. METHODS: We analyzed the data of 398 patients with CS detected in Finland from 1988 through 2017. All had clinical cardiac manifestations. Histological diagnosis was myocardial in 193 patients (definite CS) and extracardiac in 205 (probable CS). Patients with and without Class I or IIa ICD indications at presentation were identified, and subsequent occurrences of SCD (fatal or aborted) and sustained ventricular tachycardia were recorded, as were ICD indications emerging first on follow-up. RESULTS: Over a median of 4.8 years, 41 patients (10.3%) had fatal (n=8) or aborted (n=33) SCD, and 98 (24.6%) experienced SCD or sustained ventricular tachycardia as the first event. By the Heart Rhythm Society guideline, Class I or IIa ICD indications were present in 339 patients (85%) and absent in 59 (15%), of whom 264 (78%) and 30 (51%), respectively, received an ICD. Cumulative 5-year incidence of SCD was 10.7% (95% CI, 7.4%-15.4%) in patients with ICD indications versus 4.8% (95% CI, 1.2%-19.1%) in those without (χ2=1.834, P=0.176). The corresponding rates of SCD were 13.8% (95% CI, 9.1%-21.0%) versus 6.3% (95% CI, 0.7%-54.0%; χ2=0.814, P=0.367) in definite CS and 7.6% (95% CI, 3.8%-15.1%) versus 3.3% (95% CI, 0.5%-22.9%; χ2=0.680, P=0.410) in probable CS. In multivariable regression analysis, SCD was predicted by definite histological diagnosis (P=0.033) but not by Class I or IIa ICD indications (P=0.210). In patients without ICD indications at presentation, 5-year incidence of SCD, sustained ventricular tachycardia, and emerging Class I or IIa indications was 53% (95% CI, 40%-71%). By the American College of Cardiology/American Heart Association/Heart Rhythm Society guideline, all patients with complete data (n=245) had Class I or IIa indications for ICD implantation. CONCLUSIONS: Current ICD guidelines fail to distinguish a truly low-risk group of patients with clinically manifest CS, the 5-year risk of SCD approaching 5% despite absent ICD indications. Further research is needed on prognostic factors, including the role of diagnostic histology. Meanwhile, all patients with CS presenting with clinical cardiac manifestations should be considered for an ICD implantation.

Orientation of the Atrial Septum to the Inferior Vena Cava May Contribute to the Persistent Patency of the Foramen Ovale.

PURPOSE: There is growing evidence that paradoxical embolism through patent foramen ovale (PFO) is a cause for cryptogenic stroke. However, it is still unclear why the foramen ovale fails to close after birth. We studied whether the 3D relations between the atrial septum (AS) and the inferior vena cava (IVC) are associated with PFO. METHODS: We recruited 30 patients (18-49 years) with a first-ever cryptogenic stroke and 30 age- and sex-matched stroke-free controls. Using cardiac magnetic resonance, an approach to evaluate the 3D relations between the AS and the IVC was developed. The presence of interatrial right-to-left shunt was evaluated with transesophageal echocardiography (TEE) in patients and transcranial Doppler in controls. RESULTS: Of 30 patients, 29 underwent successful TEE, of which 12 (41%) had a shunt. Patients with a shunt had a greater mean 3D angle (γ) between the atrial septal plane and the vector from the orifice of the IVC to the middle of the AS compared with patients without a shunt (45 ± 9° vs. 36 ± 8°, p = 0.017). Of 30 controls, 12 (40%) had a shunt and a greater mean γ compared with controls without a shunt (47 ± 8° vs. 37 ± 10°, p = 0.007). In a pooled analysis, 24 (41%) of 59 subjects with a shunt had a mean γ of 46 ± 9° compared with subjects without a shunt of 37 ± 9° (p < 0.001). CONCLUSIONS: More perpendicular orientation of the atrial septal plane to the orifice of the IVC is associated with PFO, possibly by directing the IVC flow to PFO.

Revisiting left atrial volumetry by magnetic resonance imaging: the role of atrial shape and 3D angle between left ventricular and left atrial axis.

BACKGROUND: Accurate measurement of left atrial (LA) volumes is needed in cardiac diagnostics and the follow up of heart and valvular diseases. Geometrical assumptions with 2D methods for LA volume estimation contribute to volume misestimation. In this study, we test agreement of 3D and 2D methods of LA volume detection and explore contribution of 3D LA axis orientation and LA shape in introducing error in 2D methods by cardiovascular magnetic resonance imaging. METHODS: 30 patients with prior first-ever ischemic stroke and no known heart disease, and 30 healthy controls were enrolled (age 18-49) in a substudy of a prospective case-control study. All study subjects underwent cardiac magnetic resonance imaging and were pooled for this methodological study. LA volumes were calculated by biplane area-length method from both conventional long axis (LAVAL-LV) and LA long axis-oriented images (LAVAL-LA) and were compared to 3D segmented LA volume (LAVSAX) to assess accuracy of volume detection. 3D orientation of LA long axis to left ventricular (LV) long axis and to four-chamber plane were determined, and LA 3D sphericity indices were calculated to assess sources of error in LA volume calculation. Shapiro-Wilk test, Bland-Altman analysis, intraclass and Pearson correlation, and Spearman's rho were used for statistical analysis. RESULTS: Biases were - 9.9 mL (- 12.5 to - 7.2) for LAVAL-LV and 13.4 (10.0-16.9) for LAVAL-LA [mean difference to LAVSAX (95% confidence interval)]. End-diastolic LA long axis 3D deviation angle to LV long axis was 28.3 ± 6.2° [mean ± SD] and LA long axis 3D rotation angle to four-chamber plane 20.5 ± 18.0°. 3D orientation of LA axis or 3D sphericity were not correlated to error in LA volume calculation. CONCLUSIONS: Calculated LA volume accuracy did not improve by using LA long axis-oriented images for volume calculation in comparison to conventional method. We present novel data on LA axis orientation and a novel metric of LA sphericity and conclude that these measures cannot be utilized to assess error in LA volume calculation. TRIAL REGISTRATION: Main study Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) has been registered previously.

Right atrium and cryptogenic ischaemic stroke in the young: a case-control study.

BACKGROUND: Recent studies suggest left atrial (LA) dysfunction in cryptogenic stroke. We studied the dynamics of right atrium (RA) and right atrial appendage (RAA) in young adults with cryptogenic stroke. We hypothesised that bi-atrial dysfunction and blood stagnation might contribute to thrombosis formation in patients with patent foramen ovale (PFO), as deep venous thrombosis is detected only in the minority of patients. METHODS: Thirty patients (aged 18-49) with a first-ever cryptogenic stroke and 30 age-matched and sex-matched stroke-free controls underwent cardiac magnetic resonance (CMR) imaging. An approach to estimate the RAA volume was developed, using crista terminalis and pectinate muscles as anatomical landmarks. Atrial expansion indices were calculated as (maximal volume - minimal volume) ×100%/minimal volume. Total pulmonary to systemic blood flow ratio (Qp/Qs) was based on phase contrast CMR. Right-to-left shunt (RLS) was evaluated with transoesophageal echocardiography in 29 patients and transcranial Doppler in 30 controls, moderate-to-severe RLS considered as clinically significant. RESULTS: We found that RA and RAA volumes were similar between patients and controls. Also, RA expansion index was similar, but RAA (95.6%±21.6% vs 108.7%±25.8%, p=0.026) and LA (126.2%±28% vs 144.9%±36.3%, p=0.023) expansion indices were lower in patients compared with controls. Seven (24%) of 29 patients had an RLS compared with 1 (3%) of 30 controls (p=0.012). Among 59 study subjects, RLS was associated with lower RA (81.9%±15.9% vs 98.5%±29.5%, p=0.030), RAA (84.7%±18% vs 105.6%±24.1%, p=0.022), LA (109.8%±18.6% vs 140.1%±33.7%, p=0.017) and LAA (median 102.9% (IQR 65.6%-121.7%) vs 229.1% (151.8%-337.5%], p=0.002) expansion indices and lower Qp/Qs ratio (0.91±0.06 vs 0.98±0.07, p=0.027). CONCLUSIONS: This study suggests bi-atrial dysfunction in young adults with cryptogenic stroke, associated with moderate-to-severe RLS. Dysfunction of the atria and atrial appendages may be an additional mechanism for PFO-related stroke. TRIAL REGISTRATION NUMBER: NCT01934725.

Evidence of subtle left ventricular systolic dysfunction in cryptogenic stroke in the young.

INTRODUCTION: Ischemic stroke in young patients often remains cryptogenic, that is, no underlying reason can be found. Some of these strokes may originate in the heart. Left ventricular (LV) dynamic volumetry and strain analysis are relatively new and promising methods for evaluating LV function. METHODS: In this pilot study, we recruited 30 young (18-50 years) patients with cryptogenic ischemic stroke and 30 age- and sex-matched controls from the SECRETO study (NCT01934725). The LV systolic function was assessed by LV volumetry (ejection fraction, peak emptying rate, and time to peak emptying rate). The longitudinal systolic function was assessed by speckle tracking strain and strain rate imaging, and by tissue velocity imaging derived MAD (mitral annular displacement) and septal S'. RESULTS: Stroke patients had less vigorous global longitudinal strain (median -18.9, interquartile range 3.3), compared to healthy controls (median -20.0, interquartile range 2.8), P = .010. There was no statistically significant differences in septal S', MAD, global longitudinal strain rate, or dynamic volumetry-derived parameters between the two groups. CONCLUSIONS: Young cryptogenic stroke patients have subtly altered systolic function compared to healthy controls, found merely with longitudinal strain analysis. This infers that the heart may play a role in the pathogenesis of cryptogenic ischemic stroke.

Left ventricular non-compaction as a potential source for cryptogenic ischemic stroke in the young: A case-control study.

BACKGROUND: Up to 50% of ischemic strokes in the young after thorough diagnostic work-up remain cryptogenic or associated with low-risk sources of cardioembolism such as patent foramen ovale (PFO). We studied with cardiac magnetic resonance (CMR) imaging, whether left ventricular (LV) non-compaction-a possible source for embolic stroke due to sluggish blood flow in deep intertrabecular recesses-is associated with cryptogenic strokes in the young. METHODS: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is an international prospective multicenter case-control study of young adults (aged 18-49 years) presenting with an imaging-positive first-ever ischemic stroke of undetermined etiology. In this pilot substudy, 30 cases and 30 age- and sex-matched stroke-free controls were examined with CMR. Transcranial Doppler (TCD) bubble test was performed to evaluate the presence and magnitude of right-to-left shunt (RLS). RESULTS: There were no significant differences in LV volumes, masses or systolic function between cases and controls; none of the participants had non-compaction cardiomyopathy. Semi-automated assessment of LV non-compaction was highly reproducible. Non-compacted LV mass (median 14.0 [interquartile range 12.6-16.0] g/m2 vs. 12.7 [10.4-16.6] g/m2, p = 0.045), the ratio of non-compacted to compacted LV mass (mean 25.6 ± 4.2% vs. 22.8 ± 6.0%, p = 0.015) and the percentage of non-compacted LV volume (mean 17.6 ± 2.9% vs. 15.7 ± 3.8%, p = 0.004) were higher in cases compared to controls. In a multivariate conditional logistic regression model including non-compacted LV volume, RLS and body mass index, the percentage of non-compacted LV volume (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.10-2.18, p = 0.011) and the presence of RLS (OR 11.94, 95% CI 1.14-124.94, p = 0.038) were independently associated with cryptogenic ischemic stroke. CONCLUSIONS: LV non-compaction is associated with a heightened risk of cryptogenic ischemic stroke in young adults, independent of concomitant RLS and in the absence of cardiomyopathy. CLINICAL TRIAL REGISTRATION: SECRETO; NCT01934725. Registered 4th September 2013. https://clinicaltrials.gov/ct2/show/NCT01934725.

Diastolic function in young patients with cryptogenic stroke: A case-control pilot study.

BACKGROUND: Ischaemic stroke in young individuals often remains cryptogenic. In this pilot study, we investigated, whether advanced echocardiography methods could find differences in the diastolic function between young cryptogenic stroke patients and stroke-free controls. METHODS: We recruited 30 cryptogenic ischaemic stroke patients aged 18-49 and 30 age- and sex-matched stroke-free controls among participants of the Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO) study (NCT01934725). We measured diastolic function parameters derived from speckle tracking strain rate, Doppler techniques and 4D volumetry. We also performed statistical analyses comparing only the highest and lowest tertile of cases and controls for each parameter. RESULTS: None of our patients or controls had diastolic dysfunction according to ASE/EACVI criteria. However, compared to stroke-free controls, the stroke patient group had lower E/A ratio of mitral inflow, lower lateral and mean e', lower A/a' ratio, lower strain rate in early diastole and lower speckle tracking-derived e/a ratio. When comparing the lowest tertiles, patients also had a lower peak filling rate by 4D volumetry, a lower peak early filling fraction (fraction of left ventricular filling during early diastole), and lower velocities in a series of the tissue Doppler-derived diastolic parameters and blood flow/tissue velocity ratios. CONCLUSION: Our study displayed subtle differences in diastolic function between patients and stroke-free controls, which may play a role in early-onset cryptogenic stroke. The differences were clearer when the lowest tertiles were compared, suggesting that there is a subgroup of young cryptogenic stroke patients with subclinical heart disease.

Left Atrial Dynamics Is Altered in Young Adults With Cryptogenic Ischemic Stroke: A Case-Control Study Utilizing Advanced Echocardiography.

Background Ischemic stroke in young individuals often remains cryptogenic. Some of these strokes likely originate from the heart, and atrial fibrosis might be one of the etiological mechanisms. In this pilot study, we investigated whether advanced echocardiography findings of the left atrium (LA) of young cryptogenic stroke patients differ from those of stroke-free controls. Methods and Results We recruited 30 cryptogenic ischemic stroke patients aged 18 to 49 years and 30 age- and sex-matched stroke-free controls among participants of the SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study (NCT01934725). We measured basic left ventricular parameters and detailed measures of the LA, including 4-dimensional volumetry, speckle tracking epsilon, strain rate, and LA appendix orifice variation. Data were compared as continuous parameters and by tertiles. Compared with controls, stroke patients had smaller LA reservoir volumes (10.2 [interquartile range, 5.4] versus 13.2 [5.4] mL; P=0.030) and smaller positive epsilon values (17.8 [8.5] versus 20.8 [10.1]; P=0.023). In the tertile analysis, stroke patients had significantly lower left atrial appendage orifice variation (3.88 [0.75] versus 4.35 [0.90] mm; P=0.043), lower LA cyclic volume change (9.2 [2.8] versus 12.8 [3.5] mL; P=0.023), and lower LA contraction peak strain rate (-1.8 [0.6] versus -2.3 [0.6]; P=0.021). We found no statistically significant differences in left ventricular measures. Conclusions This preliminary comparison suggests altered LA dynamics in young patients with cryptogenic ischemic stroke, and thus that LA wall pathology might contribute to these strokes. Our results await confirmation in a larger sample.

Peak CK-MB has a strong association with chronic scar size and wall motion abnormalities after revascularized non-transmural myocardial infarction - a prospective CMR study.

BACKGROUND: Large myocardial infarction (MI) is associated with adverse left ventricular (LV) remodeling (LVR). We studied the nature of LVR, with specific attention to non-transmural MIs, and the association of peak CK-MB with recovery and chronic phase scar size and LVR. METHODS: Altogether 41 patients underwent prospectively repeated cardiovascular magnetic resonance at a median of 22 (interquartile range 9-29) days and 10 (8-16) months after the first revascularized MI. Transmural MI was defined as ≥75% enhancement in at least one myocardial segment. RESULTS: Peak CK-MB was 86 (40-216) µg/L in median, while recovery and chronic phase scar size were 13 (3-23) % and 8 (2-19) %. Altogether 33 patients (81%) had a non-transmural MI. Peak CK-MB had a strong correlation with recovery and chronic scar size (r ≥ 0.80 for all, r ≥ 0.74 for non-transmural MIs; p < 0.001). Peak CK-MB, recovery scar size, and chronic scar size, were all strongly correlated with chronic wall motion abnormality index (WMAi) (r ≥ 0.75 for all, r ≥ 0.73 for non-transmural MIs; p < 0.001). There was proportional scar size and LV mass resorption of 26% (0-50%) and 6% (- 2-14%) in median. Young age (< 60 years, median) was associated with greater LV mass resorption (median 9%vs.1%, p = 0.007). CONCLUSIONS: Peak CK-MB has a strong association with chronic scar size and wall motion abnormalities after revascularized non-transmural MI. Considerable infarct resorption happens after the first-month recovery phase. LV mass resorption is related to age, being more common in younger patients.

Cardiovascular magnetic resonance findings in patients with PRKAG2 gene mutations.

BACKGROUND: Autosomal dominantly inherited PRKAG2 cardiac syndrome is due to a unique defect of the cardiac cell metabolism and has a distinctive histopathology with excess intracellular glycogen, and prognosis different from sarcomeric hypertrophic cardiomyopathy. We aimed to define the distinct characteristics of PRKAG2 using cardiovascular magnetic resonance (CMR). METHODS: CMR (1.5 T) and genetic testing were performed in two families harboring PRKAG2 mutations. On CMR, segmental analysis of left ventricular (LV) hypertrophy (LVH), function, native T1 mapping, and late gadolinium enhancement (LGE) were performed. RESULTS: Six individuals (median age 23 years, range 16-48; two females) had a PRKAG2 mutation: five with an R302Q mutation (family 1), and one with a novel H344P mutation (family 2). Three of six mutation carriers had LV mass above age and gender limits (203 g/m2, 157 g/m2 and 68 g/m2) and others (with R302Q mutation) normal LV masses. All mutation carriers had LVH in at least one segment, with the median maximal wall thickness of 13 mm (range 11-37 mm). Two R302Q mutation carriers with markedly increased LV mass (203 g/m2 and 157 g/m2) showed a diffuse pattern of hypertrophy but predominantly in the interventricular septum, while other mutation carriers exhibited a non-symmetric mid-infero-lateral pattern of hypertrophy. In family 1, the mutation negative male had a mean T1 value of 963 ms, three males with the R302Q mutation, LVH and no LGE a mean value of 918 ± 11 ms, and the oldest male with the R302Q mutation, extensive hypertrophy and LGE a mean value of 973 ms. Of six mutations carriers, two with advanced disease had LGE with 11 and 22 % enhancement of total LV volume. CONCLUSIONS: PRKAG2 cardiac syndrome may present with eccentric distribution of LVH, involving focal mid-infero-lateral pattern in the early disease stage, and more diffuse pattern but focusing on interventricular septum in advanced cases. In patients at earlier stages of disease, without LGE, T1 values may be reduced, while in the advanced disease stage T1 mapping may result in higher values caused by fibrosis. CMR is a valuable tool in detecting diffuse and focal myocardial abnormalities in PRKAG2 cardiomyopathy.

Quantifying late gadolinium enhancement on CMR provides additional prognostic information in early risk-stratification of nonischemic cardiomyopathy: a cohort study.

BACKGROUND: Suspected nonischemic cardiomyopathy (NICM) is a common clinical setting with highly variable prognosis. Early noninvasive risk-stratification is important for justification of invasive examinations, specific treatment and patient surveillance. We studied the additional prognostic value of late gadolinium enhancement (LGE) and segmental wall motion abnormality (SWMA) extent on cardiovascular magnetic resonance (CMR) compared to traditional risk factors in suspected NICM. METHODS: In this observational cohort study, we enrolled 86 consecutive patients referred for CMR due to suspected NICM. Patients with ischemic cardiomyopathy were excluded. CMR images were analysed for left ventricular LGE and SWMA extents and patients were followed-up for major adverse cardiac events (MACE), including cardiovascular death, aborted sudden death and cardiac transplantation. RESULTS: Of 86 patients (median age: 53 years, 45% female), mainly presenting with ventricular arrhythmias (40%) and congestive heart failure (44%), 76% were finally diagnosed with NICM, 17% with left ventricle hypertrophy and 7% with idiopathic arrhythmia. On CMR, 61 patients (71%) had LGE and 56 (65%) SWMA. During median follow-up of 835 days, 15 patients (17%) reached MACE. In univariant analysis, LGE volume (hazard ratio [HR] 1.028 per 1% increase in LGE, p < 0.001), left ventricular ejection fraction (LVEF) (HR 0.959, p = 0.009) and SWMA score (HR 1.067, p = 0.012) had strongest associations with MACE. In multivariate analysis, the best overall model for event prediction included LGE volume (HR 1.027, p = 0.003), sustained ventricular tachycardia (HR 4.7, p = 0.011) and LVEF (HR 0.962, p = 0.034). Among patients with LGE, there was an event rate of 26% (14 of 61) versus 4% (1 of 25) in patients without LGE (p = 0.041, Log-rank). The highest event rate was observed in patients with LGE volume of ≥ 17%. Patients without SWMA did not experience MACE (p = 0.002, Log-rank), giving additional information in the subgroup of patients with preserved LVEF (≥ 50%). CONCLUSIONS: In suspected NICM, presenting with ventricular arrhythmias or heart failure, LGE extent gives additional prognostic information compared to traditional risk factors, while the absence of SWMA may give prognostic information beyond normal LVEF. Even though the final diagnosis is uncertain in NICM, extensive amount of LGE should be considered as a sign of poor prognosis.

Late gadolinium enhancement on CMR and sustained ventricular tachycardia predict severe cardiac inflammation.

OBJECTIVE: Early diagnosis of severe inflammatory forms of non-ischaemic cardiomyopathy (NICM), e.g. cardiac sarcoidosis (CS) or giant cell myocarditis (GCM), may enable unique treatment. However, there is limited information on how to identify CS or GCM in unselected patients with suspected NICM. We studied the clinical and imaging predictors of severe cardiac inflammation at the era of late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). METHODS AND RESULTS: In this observational cohort study, we enrolled 86 consecutive patients referred for LGE-CMR due to suspected NICM. Patients were extensively examined for underlying aetiology and followed up for at least two years to assure the final diagnosis. Ischaemic cardiomyopathy was excluded. During follow-up, 11(13%) patients were diagnosed with CS (n = 8) or GCM (n = 3). At baseline, sustained ventriculartachycardia (OR = 20.8, P = 0.001) and the volume of left ventricular LGE (OR = 1.06 for each 1% increase in LGE, P = 0.001) were significant adjusted predictors of CS or GCM. Palpitation, a disease course less than 3 months, septal abnormality in echocardiography, reduced stroke volume and atrioventricular block were other unadjusted predictors of CS or GCM. Multifocal LGE, affecting several myocardial layers and not confined to coronary artery perfusion territories, was useful in identifying CS or GCM, with 52-fold unadjusted OR (P < 0.001), sensitivity of 91% and specificity of 84%. In addition, positron emission tomography detected mediastinal lymph node biopsy targets in CS. CONCLUSIONS: In consecutive patients suspected for NICM, LGE volume and sustained ventricular tachycardia predict independently CS or GCM. Multifocal LGE is useful in identifying severe cardiac inflammation.