Joseph Suttie

Myocardial Tissue Characterization Using Magnetic Resonance Noncontrast T1 Mapping in Hypertrophic and Dilated Cardiomyopathy

Background—Noncontrast magnetic resonance T1 mapping reflects a composite of both intra- and extracellular signal. We hypothesized that noncontrast T1 mapping can characterize the myocardium beyond that achieved by the well-established late gadolinium enhancement (LGE) technique (which detects focal fibrosis) in both hypertrophic (HCM) and dilated (DCM) cardiomyopathy, by detecting both diffuse and focal fibrosis. Methods and Results—Subjects underwent Cardiovascular Magnetic Resonance imaging at 3T (28 HCM, 18 DCM, and 12 normals). Matching short-axis slices were acquired for cine, T1 mapping, and LGE imaging (0.1 mmol/kg). Circumferential strain was measured in the midventricular slice, and 31P magnetic resonance spectroscopy was acquired for the septum of the midventricular slice. Mean T1 relaxation time was increased in HCM and DCM (HCM 1209±28 ms, DCM 1225±42 ms, normal 1178±13 ms, P<0.05). There was a weak correlation between mean T1 and LGE (r=0.32, P<0.001). T1 values were higher in segments with LGE than in those without (HCM with LGE 1228±41 ms versus no LGE 1192±79 ms, P<0.01; DCM with LGE 1254±73 ms versus no LGE 1217±52 ms, P<0.01). However, in both HCM and DCM, even in segments unaffected by LGE, T1 values were significantly higher than normal (P<0.01). T1 values correlated with disease severity, being increased as wall thickness increased in HCM; conversely, in DCM, T1 values were highest in the thinnest myocardial segments. T1 values also correlated significantly with circumferential strain (r=0.42, P<0.01). Interestingly, this correlation remained statistically significant even for the slices without LGE (r=0.56, P=0.04). Finally, there was also a statistically significant negative correlation between T1 values and phosphocreatine/adenosine triphosphate ratios (r=−0.59, P<0.0001). Conclusions—In HCM and DCM, noncontrast T1 mapping detects underlying disease processes beyond those assessed by LGE in relatively low-risk individuals.

Comprehensive Cardiac Magnetic Resonance Imaging and Spectroscopy Reveal a High Burden of Myocardial Disease in HIV Patients

Background— HIV infection continues to be endemic worldwide. Although treatments are successful, it remains controversial whether patients receiving optimal therapy have structural, functional, or biochemical cardiac abnormalities that may underlie their increased cardiac morbidity and mortality. The purpose of this study was to characterize myocardial abnormalities in a contemporary group of HIV-infected individuals undergoing combination antiretroviral therapy. Methods and Results— Volunteers with HIV who were undergoing combination antiretroviral therapy and age-matched control subjects without a history of cardiovascular disease underwent cardiac magnetic resonance imaging and spectroscopy for the determination of cardiac function, myocardial fibrosis, and myocardial lipid content. A total of 129 participants were included in this analysis. Compared with age-matched control subjects (n=39; 30.23%), HIV-infected subjects undergoing combination antiretroviral therapy (n=90; 69.77%) had 47% higher median myocardial lipid levels (P <0.003) and 74% higher median plasma triglyceride levels (both P<0.001). Myocardial fibrosis, predominantly in the basal inferolateral wall of the left ventricle, was observed in 76% of HIV-infected subjects compared with 13% of control subjects (P<0.001). Peak myocardial systolic and diastolic longitudinal strain were also lower in HIV-infected individuals than in control subjects and remained statistically significant after adjustment for available confounders. Conclusions— Comprehensive cardiac imaging revealed cardiac steatosis, alterations in cardiac function, and a high prevalence of myocardial fibrosis in a contemporary group of asymptomatic HIV-infected subjects undergoing combination antiretroviral therapy. Cardiac steatosis and fibrosis may underlie cardiac dysfunction and increased cardiovascular morbidity and mortality in subjects with HIV.

7 Tesla (T) human cardiovascular magnetic resonance imaging using FLASH and SSFP to assess cardiac function: validation against 1.5 T and 3 T

We report the first comparison of cardiovascular magnetic resonance imaging (CMR) at 1.5 T, 3 T and 7 T field strengths using steady state free precession (SSFP) and fast low angle shot (FLASH) cine sequences. Cardiac volumes and mass measurements were assessed for feasibility, reproducibility and validity at each given field strength using FLASH and SSFP sequences. Ten healthy volunteers underwent retrospectively electrocardiogram (ECG) gated CMR at 1.5 T, 3 T and 7 T using FLASH and SSFP sequences. B1 and B0 shimming and frequency scouts were used to optimise image quality. Cardiac volume and mass measurements were not significantly affected by field strength when using the same imaging sequence (P > 0.05 for all parameters at 1.5 T, 3 T and 7 T). SSFP imaging returned larger end diastolic and end systolic volumes and smaller left ventricular masses than FLASH imaging at 7 T, and at the lower field strengths (P < 0.05 for each parameter). However, univariate general linear model analysis with fixed effects for sequence and field strengths found an interaction between imaging sequence and field strength (P = 0.03), with a smaller difference in volumes and mass measurements between SSFP and FLASH imaging at 7 T than 1.5 T and 3 T. SSFP and FLASH cine imaging at 7 T is technically feasible and provides valid assessment of cardiac volumes and mass compared with CMR imaging at 1.5 T and 3 T field strengths. Copyright

Myocardial steatosis and left ventricular contractile dysfunction in patients with severe aortic stenosis.

Background— Aortic stenosis (AS) leads to left ventricular (LV) hypertrophy and dysfunction. We hypothesized that cardiac steatosis is involved in the pathophysiology and also assessed whether it is reversible after aortic valve replacement. Methods and Results— Thirty-nine patients with severe AS (symptomatic=25, asymptomatic=14) with normal LV ejection fraction and no significant coronary artery disease and 20 age- and sex-matched healthy controls underwent cardiac 1H-magnetic resonance spectroscopy and imaging for the determination of steatosis (myocardial triglyceride content) and cardiac function, including circumferential strain (measured by magnetic resonance tagging). Strain was lower in both symptomatic and asymptomatic AS (−16.4±2.5% and −18.1±2.9%, respectively, versus controls −20.7±2.0%, both P<0.05). Myocardial steatosis was found in both symptomatic and asymptomatic patients with AS (0.89±0.42% in symptomatic AS; 0.75±0.36% in asymptomatic AS versus controls 0.45±0.17, both P<0.05). Importantly, multivariable analysis indicated that steatosis was an independent correlate of impaired LV strain. Spectroscopic measurements of myocardial triglyceride content correlated significantly with histological analysis of biopsies obtained during aortic valve replacement. At 8.0±2.1 months after aortic valve replacement, steatosis and strain had recovered toward normal. Conclusions— Pronounced myocardial steatosis is present in severe AS, regardless of symptoms, and is independently associated with the degree of LV strain impairment. Myocardial triglyceride content measured by magnetic resonance spectroscopy correlates with histological quantification. Steatosis and strain impairment are reversible after aortic valve replacement. Our findings suggest a novel pathophysiological mechanism in AS, myocardial steatosis, which may be amenable to treatment, thus potentially delaying onset of LV dysfunction.

Blunted Myocardial Oxygenation Response During Vasodilator Stress in Patients With Hypertrophic Cardiomyopathy

Objectives This study sought to assess myocardial perfusion and tissue oxygenation during vasodilator stress in patients with overt hypertrophic cardiomyopathy (HCM), as well as in HCM mutation carriers without left ventricular (LV) hypertrophy, and to compare findings to those in athletes with comparable hypertrophy and normal controls. Background Myocardial perfusion under vasodilator stress is impaired in patients with HCM. Whether this is associated with impaired myocardial oxygenation and tissue ischemia is unknown. Furthermore, it is not known whether perfusion and oxygenation are impaired in HCM mutation carriers without left ventricular hypertrophy (LVH). Methods A total of 27 patients with overt HCM, 10 HCM mutation carriers without LVH, 11 athletes, and 20 healthy controls underwent cardiovascular magnetic resonance (CMR) scanning at 3-T. Myocardial function, perfusion (perfusion reserve index [MPRI]), and oxygenation (blood-oxygen level dependent signal intensity [SI] change) under adenosine stress were assessed. Results MPRI was significantly reduced in HCM (1.3 ± 0.1) compared to controls (1.8 ± 0.1, p < 0.001) and athletes (2.0 ± 0.1, p < 0.001), but remained normal in HCM mutation carriers without LVH (1.7 ± 0.1; p = 0.61 vs. controls, p = 0.02 vs. overt HCM). Oxygenation response was attenuated in overt HCM (SI change 6.9 ± 1.4%) compared to controls (18.9 ± 1.4%, p < 0.0001) and athletes (18.7 ± 2.0%, p < 0.001). Interestingly, HCM mutation carriers without LVH also showed an impaired oxygenation response to adenosine (10.4 ± 2.0%; p = 0.001 vs. controls, p = 0.16 vs. overt HCM, p = 0.003 vs. athletes). Conclusions In overt HCM, both perfusion and oxygenation are impaired during vasodilator stress. However, in HCM mutation carriers without LVH, only oxygenation is impaired. In athletes, stress perfusion and oxygenation are normal. CMR assessment of myocardial oxygenation has the potential to become a novel risk factor in HCM.

Clinical Cardiac Magnetic Resonance Spectroscopy

Cardiac magnetic resonance spectroscopy (MRS) is a noninvasive tool for the assessment of myocardial metabolism, without the use of radiation or intravenous contrast agents. Using the intrinsic magnetic resonance signals from nuclei, including (31)Phosphorus, (1)Hydrogen, (23)Sodium, and (13)Carbon and, more recently, hyperpolarization techniques, MRS provides a comprehensive metabolic assessment of cardiac muscle. This highly versatile technique has provided insights into the pathophysiology of cardiac metabolism in a wide range of conditions, including ischemic heart disease, heart failure, genetic cardiomyopathies, heart transplantation, hypertensive heart disease, valvular heart disease, and diabetes. In addition, MRS has value in the assessment of prognosis and for monitoring therapeutic strategies in heart failure. However, because of the low temporal and spatial resolution of the technique, MRS has so far been limited to research applications. With higher field strength magnets and novel hyperpolarization techniques, the promise of using MRS for clinical applications may eventually be fulfilled.

Exacerbation of cardiac energetic impairment during exercise in hypertrophic cardiomyopathy: a potential mechanism for diastolic dysfunction

AIMS Hypertrophic cardiomyopathy (HCM) is the commonest cause of sudden cardiac death in the young, with an excess of exercise-related deaths. The HCM sarcomere mutations increase the energy cost of contraction and impaired resting cardiac energetics has been documented by measurement of phosphocreatine/ATP (PCr/ATP) using (31)Phosphorus MR Spectroscopy ((31)P MRS). We hypothesized that cardiac energetics are further impaired acutely during exercise in HCM and that this would have important functional consequences. METHODS AND RESULTS (31)P MRS was performed in 35 HCM patients and 20 age- and gender-matched normal volunteers at rest and during leg exercise with 2.5 kg ankle weights. Peak left-ventricular filling rates (PFRs) and myocardial perfusion reserve (MPRI) were calculated during adenosine stress. Resting PCr/ATP was significantly reduced in HCM (HCM: 1.71 ± 0.35, normal 2.14 ± 0.35 P < 0.0001). During exercise, there was a further reduction in PCr/ATP in HCM (1.56 ± 0.29, P = 0.02 compared with rest) but not in normals (2.16 ± 0.26, P = 0.98 compared with rest). There was no correlation between PCr/ATP reduction and cardiac mass, wall thickness, MPRI, or late-gadolinium enhancement. PFR and PCr/ATP were significantly correlated at rest (r = 0.48, P = 0.02) and stress (r = 0.53, P = 0.01). CONCLUSION During exercise, the pre-existing energetic deficit in HCM is further exacerbated independent of hypertrophy, perfusion reserve, or degree of fibrosis. This is in keeping with the change at the myofilament level. We offer a potential explanation for exercise-related diastolic dysfunction in HCM.

The effects of excess weight on cardiac strain and steatosis in adults and children

Background Excess body fat is a known risk factor for cardiovascular mortality and morbidity. However, obesity, hypertension, hyperlipidaemia and insulin resistance are closely interlinked, both in their causes (eg sedentary lifestyle, social class, diet & age) and effects (endothelial function, increased left ventricular mass, increased myocardial fatty acid uptake). Thus it has been difficult to determine the exact effects of excess weight alone on myocardial function and metabolism. Myocardial triglyceride deposition and impaired strain have been clearly shown in adult diabetic cardiomyopathy. Recently, similar findings have been demonstrated in obese non-diabetic women. We set out to see if obesity alone, in the absence of other components of the Metabolic Syndrome, was also associated with cardiac steatosis and/or impaired peak circumferential strain in adults of both sexes and in adolescent boys. Methods We recruited 100 adults (44 lean, 28 overweight & 28 obese) and 22 boys aged 10-15 years (11 lean & 11 obese) by open poster advertisement. Exclusion criteria were heart failure, valvular disease, the use of any cardiovascular medications and any classical risk factors (hypertension, hyperlipidaemia, diabetes mellitus, smoking and obstructive sleep apnoea). Body mass index (BMI) and waist circumference were measured in all subjects. Left ventricular (LV) mass, volumes, function and peak circumferential strain were measured with 3T cardiac MR imaging and tagging. Myocardial triglyceride content (MTGC) was determined by ECG-gated localised proton spectroscopy to calculate the lipid : water ratio in the interventricular septum. Image and spectroscopy data were anonymised prior to analysis. Results There was a clear increase in myocardial lipid content in overweight and obese adults compared to the lean control group (Figure 1). Body mass index and waist circumference were associated with a linear increase in MTGC (a 10kg/m 2 increase in BMI was associated with a 48% increase in MTGC, p < 0.05), but gender had no impact. There was also an 11% reduction in the peak circumferential strain of obese adults compared to their lean peers (median -18.0 v -21.4, p = 0.01), despite similar LV ejection fractions. LV mass was 16% higher in overweight and 20% higher in obese adults (p <0.01). In the adolescent group, obese boys had higher mean myocardial triglyceride deposition (0.29% v 0.16%, p = 0.04) and impaired strain (-17.5 v -20.2, p < 0.01), but with no significant difference in LV mass, ejection fraction, end-diastolic volume, glucose or cholesterol (Figure 2). Conclusions Obesity in the absence of diabetes or Metabolic Syndrome is associated with significant myocardial triglyceride deposition and impaired strain in adults and children. In paediatric obesity, this data suggests that myocardial steatosis and change in strain occur before any hypertrophy. The assessment of strain and MTGC may help in the diagnosis and monitoring of obesityrelated heart disease, especially in children.

Dystrophinopathies are characterised by impaired cardiac metabolism, contractile dysfunction and fibrosis in patients with and without coxsackie B3 exposure

Inherited dystrophinopathies (Becker and Duchenne muscular dystrophy, and females with heterozygous mutations) have a high rate of myocardial disease with a variable clinical phenotype. We have previously demonstrated that dystrophinopathic patients have significantly impaired myocardial energetics and fibrosis even in the presence of normal left ventricular ejection fraction. Furthermore, Coxsackie B3 induced viral cardiomyopathy has been shown to be a form of acquired dystrophinopathy.

Visualisation of aortic flow disturbance in Marfan syndrome by 4D phase-contrast CMR

Methods 15 patients with Marfan syndrome and no history of prior aortic dissection or surgery, and 18 healthy volunteer controls matched for age, sex and height underwent CMR at 3T (Siemens, Erlangen). Time-resolved, 3D velocity-encoded and magnitude data were acquired using a phase contrast CMR sequence (Figure 2). Each dataset was evaluated for flow disturbance by two independent observers, experienced in aortic flow visualisation, and blinded to patient identity.