Laura E K Ratcliffe

Comprehensive characterisation of hypertensive heart disease left ventricular phenotypes

Objective Myocardial intracellular/extracellular structure and aortic function were assessed among hypertensive left ventricular (LV) phenotypes using cardiovascular magnetic resonance (CMR). Methods An observational study from consecutive tertiary hypertension clinic patients referred for CMR (1.5 T) was performed. Four LV phenotypes were defined: (1) normal with normal indexed LV mass (LVM) and LVM to volume ratio (M/V), (2) concentric remodelling with normal LVM but elevated M/V, (3) concentric LV hypertrophy (LVH) with elevated LVM but normal indexed end-diastolic volume (EDV) or (4) eccentric LVH with elevated LVM and EDV. Extracellular volume fraction was measured using T1-mapping. Circumferential strain was calculated by voxel-tracking. Aortic distensibility was derived from high-resolution aortic cines and contemporaneous blood pressure measurements. Results 88 hypertensive patients (49±14u2005years, 57% men, systolic blood pressure (SBP): 167±30u2005mmu2005Hg, diastolic blood pressure (DBP): 96±14u2005mmu2005Hg) were compared with 29 age-matched/sex-matched controls (47±14u2005years, 59% men, SBP: 128±12u2005mmu2005Hg, DBP: 79±10u2005mmu2005Hg). LVH resulted from increased myocardial cell volume (eccentric LVH: 78±19u2005mL/m2 vs concentric LVH: 73±15u2005mL/m2 vs concentric remodelling: 55±9u2005mL/m2, p<0.05, respectively) and interstitial fibrosis (eccentric LVH: 33±10u2005mL/m2 vs concentric LVH: 30±10u2005mL/m2 vs concentricremodelling: 19±2u2005mL/m2, p<0.05, respectively). LVH had worst circumferential impairment (eccentric LVH: −12.8±4.6% vs concentric LVH: −15.5±3.1% vs concentric remodelling: –17.1±3.2%, p<0.05, respectively). Concentric remodelling was associated with reduced aortic distensibility, but not with large intracellular/interstitial expansion or myocardial dysfunction versus controls. Conclusions Myocardial interstitial fibrosis varies across hypertensive LV phenotypes with functional consequences. Eccentric LVH has the most fibrosis and systolic impairment. Concentric remodelling is only associated with abnormal aortic function. Understanding these differences may help tailor future antihypertensive treatments.

ECG strain pattern in hypertension is associated with myocardial cellular expansion and diffuse interstitial fibrosis: a multi-parametric cardiac magnetic resonance study

Aims In hypertension, the presence of left ventricular (LV) strain pattern on 12-lead electrocardiogram (ECG) carries adverse cardiovascular prognosis. The underlying mechanisms are poorly understood. We investigated whether hypertensive ECG strain is associated with myocardial interstitial fibrosis and impaired myocardial strain, assessed by multi-parametric cardiac magnetic resonance (CMR). Methods and results A total of 100 hypertensive patients [50 ± 14 years, male: 58%, office systolic blood pressure (SBP): 170 ± 30 mmHg, office diastolic blood pressure (DBP): 97 ± 14 mmHg) underwent ECG and 1.5T CMR and were compared with 25 normotensive controls (46 ± 14 years, 60% male, SBP: 124 ± 8 mmHg, DBP: 76 ± 7 mmHg). Native T1 and extracellular volume fraction (ECV) were calculated with the modified look-locker inversion-recovery sequence. Myocardial strain values were estimated with voxel-tracking software. ECG strain (n = 20) was associated with significantly higher indexed LV mass (LVM) (119 ± 32 vs. 80 ± 17 g/m2, P < 0.05) and ECV (30 ± 4 vs. 27 ± 3%, P < 0.05) compared with hypertensive subjects without ECG strain (n = 80). ECG strain subjects had significantly impaired circumferential strain compared with hypertensive subjects without ECG strain and controls (−15.2 ± 4.7 vs. −17.0 ± 3.3 vs. −17.3 ± 2.4%, P < 0.05, respectively). In subgroup analysis, comparing ECG strain subjects to hypertensive subjects with elevated LVM but no ECG strain, a significantly higher ECV (30 ± 4 vs. 28 ± 3%, P < 0.05) was still observed. Indexed LVM was the only variable independently associated with ECG strain in multivariate logistic regression analysis [odds ratio (95th confidence interval): 1.07 (1.02–1.12), P < 0.05). Conclusion In hypertension, ECG strain is a marker of advanced LVH associated with increased interstitial fibrosis and associated with significant myocardial circumferential strain impairment.

The effect of obesity on electrocardiographic detection of hypertensive left ventricular hypertrophy: recalibration against cardiac magnetic resonance.

Electrocardiograph (ECG) criteria for left ventricular hypertrophy (LVH) are a widely used clinical tool. We recalibrated six ECG criteria for LVH against gold-standard cardiac magnetic resonance (CMR) and assessed the impact of obesity. One hundred and fifty consecutive tertiary hypertension clinic referrals for CMR (1.5u2009T) were reviewed. Patients with cardiac pathology potentially confounding hypertensive LVH were excluded (n=22). The final sample size was 128 (age: 51.0±15.2 years, 48% male). LVH was defined by CMR. From a 12-lead ECG, Sokolow–Lyon voltage and product, Cornell voltage and product, Gubner–Ungerleidger voltage and Romhilt–Estes score were evaluated, blinded to the CMR. ECG diagnostic performance was calculated. LVH by CMR was present in 37% and obesity in 51%. Obesity significantly reduced ECG sensitivity, because of significant attenuation in mean ECG values for Cornell voltage (22.2±5.7 vs 26.4±9.4u2009mm, P<0.05), Cornell product (2540±942 vs 3023±1185u2009mmu2009•u2009ms, P<0.05) and for Gubner–Ungerleider voltage (18.2±7.1 vs 23.3±1.2u2009mm, P<0.05). Obesity also significantly reduced ECG specificity, because of significantly higher prevalence of LV remodeling (no LVH but increased mass-to-volume ratio) in obese subjects without LVH (36% vs 16%, P<0.05), which correlated with higher mean ECG LVH criteria values. Obesity-specific partition values were generated at fixed 95% specificity; Cornell voltage had highest sensitivity in non-obese (56%) and Sokolow–Lyon product in obese patients (24%). Obesity significantly lowers ECG sensitivity at detecting LVH, by attenuating ECG LVH values, and lowers ECG specificity through changes associated with LV remodeling. Our obesity-specific ECG partition values could improve the diagnostic performance in obese patients with hypertension.

Comprehensive First‐Line Magnetic Resonance Imaging in Hypertension: Experience From a Single‐Center Tertiary Referral Clinic

European guidelines recommend that patients with hypertension be assessed for asymptomatic organ damage and secondary causes. The authors propose that a single magnetic resonance imaging (MRI) scan can provide comprehensive first‐line imaging of patients assessed via a specialist hypertension clinic. A total of 200 patients (56% male, aged 51±15 years, office BP 168±30/96±16 mm Hg) underwent MRI of the heart, kidneys, renal arteries, adrenals and aorta. Comparisons were made with other imaging modalities where available. A total of 61% had left ventricular hypertrophy (LVH), 14% had reduced ejection fraction, and 15 patients had myocardial infarcts. Echocardiography overdiagnosed LVH in 15% of patients and missed LVH in 14%. Secondary causes were identified in 14.5% of patients: 12 adrenal masses, 10 renal artery stenoses, seven thyroid abnormalities, one aortic coarctation, one enlarged pituitary gland, one polycystic kidney disease, and one renal coloboma syndrome. This comprehensive MRI protocol is an effective method of screening for asymptomatic organ damage and secondary causes of hypertension.

Controversies Surrounding Renal Denervation: Lessons Learned From Real-World Experience in Two United Kingdom Centers

Renal denervation (RDN) is a therapy that targets treatment‐resistant hypertension (TRH). The Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity) HTN‐1 and Symplicity HTN‐2 trials reported response rates of >80%; however, sham‐controlled Symplicity HTN‐3 failed to reach its primary blood pressure (BP) outcome. The authors address the current controversies surrounding RDN, illustrated with real‐world data from two centers in the United Kingdom. In this cohort, 52% of patients responded to RDN, with a 13±32 mm Hg reduction in office systolic BP (SBP) at 6 months (n=29, P=.03). Baseline office SBP and number of ablations correlated with office SBP reduction (R=−0.47, P=.01; R=−0.56, P=.002). RDN appears to be an effective treatment for some patients with TRH; however, individual responses are highly variable. Selecting patients for RDN is challenging, with only 10% (33 of 321) of the screened patients eligible for the study. Medication alterations and nonadherence confound outcomes. Adequate ablation is critical and should impact future catheter design/training. Markers of procedural success and improved patient selection parameters remain key research aims.

Phenotyping patterns of left ventricular remodeling and hypertrophy in systemic hypertension by cardiac magnetic resonance (CMR).

Methods Consecutive patients referred from our tertiary hypertension clinic, who underwent CMR at 1.5T, were included. Exclusion criteria included patients with clinical or CMR evidence of concomitant pathology (e.g. moderate-severe aortic stenosis) which may confound remodeling/hypertrophy pattern. Indexed LVM (iLVM), including papillary muscle mass by blood pool thresholding, indexed LV enddiastolic volume (iEDV) and ejection fraction (EF) were calculated using established CMR methods and normalized to body surface area. Values out-with the 95 th confidence intervals of established CMR normal reference values were considered abnormal. Mass : volume ratio (M/ V) >1.12 for men and >1.14 for women was defined as abnormal, in accordance with previous literature. The phenotypes of ventricular remodeling and hypertrophy were defined as either normal, concentric remodeling, asymmetric remodeling, concentric hypertrophy, asymmetric hypertrophy, eccentric hypertrophy or decompensation depending on the constellation of iLVM, iEDV, M/V, asymmetric thickness (>13mm and >1.5 fold opposing wall) and EF Results One hundred and twenty three (n=123) patients were analysed. The prevalence of different phenotypical responses were as follows: normal (42.3%), concentric remodeling (6.5%), asymmetric remodeling (5.7%), concentric hypertrophy (12.2%), asymmetric hypertrophy (17.9%) eccentric hypertrophy (8.9%) and decompensation (6.5%). The demographic and CMR characteristics of the different types of remodeling and hypertrophy are described in Figure 1. There was no predilection of remodeling/hypertrophic pattern according to hypertension type. 12.2% of our cohort had normal iLVM but demonstrated concentric/asymmetric remodeling. Subgroup analysis by remodeling (n=15) versus hypertrophy (n=22) revealed no significant difference in age (62±9.4 vs 55.1±12.4 years, p=0.0598), gender (% male 74.4% vs 68.2%, p=0.999), BMI (30.9±3.0 vs 30.1±4.9 kg/m 2 , p=0.5836), degree of hypertension (SBP 179.9±31.3 vs 176.8±24.7 mmHg, p=0.7407 and DBP 98.4±11.4 vs 95.7±14.8 mmHg, p=0.5557) or prevalence of potentially remodeling modifying medication (ACEi/ARB 80.0% vs 77.3%, p=0.999). Conclusions Varied CMR patterns of LV remodeling/hypertrophy occur in hypertensive patients with no predilection demonstrated in subgroup analysis. CMR-derived iLVM is increasingly used an end-point for clinical trials in hypertension. Our data suggest that patterns of LV remodeling/ hypertrophy should also be taken into account to avoid misclassifying patients with normal iLVM (but abnormal ventricles due to remodeling) together with patients with normal iLVM and truly normal ventricles.

Noctural dipping status and left ventricular hypertrophy: A cardiac magnetic resonance imaging study

We investigate the impact of dipper status on cardiac structure with cardiovascular magnetic resonance (CMR). Ambulatory blood pressure monitoring and 1.5T CMR were performed in 99 tertiary hypertension clinic patients. Subgroup analysis by extreme dipper (n = 9), dipper (n = 39), non‐dipper (n = 35) and reverse dipper (n = 16) status was performed, matched in age, gender and BMI. Left ventricular (LV) mass was significantly higher for extreme dippers than dippers after correction for covariates (100 ± 6 g/m2 vs 79 ± 3 g/m2, P = .004). Amongst extreme dippers and dippers (n = 48), indexed LV mass correlated positively with the extent of nocturnal blood pressure dipping (R = .403, P = .005). On post‐hoc ANCOVA, the percentage of nocturnal dip had significant effect on indexed LV mass (P = .008), but overall SBP did not (P = .348). In the tertiary setting, we found a larger nocturnal BP drop was associated with more LV hypertrophy. If confirmed in larger studies, this may have implications on nocturnal dosing of anti‐hypertensive medications.

The relationship between left ventricular wall thickness, myocardial shortening and ejection fraction in hypertensive heart disease

Hypertensive heart disease is often associated with a preserved left ventricular ejection fraction despite impaired myocardial shortening. The authors investigated this paradox in 55 hypertensive patients (52±13 years, 58% male) and 32 age‐ and sex‐matched normotensive control patients (49±11 years, 56% male) who underwent cardiac magnetic resonance imaging at 1.5T. Long‐axis shortening (R=0.62), midwall fractional shortening (R=0.68), and radial strain (R=0.48) all decreased (P<.001) as end‐diastolic wall thickness increased. However, absolute wall thickening (defined as end‐systolic minus end‐diastolic wall thickness) was maintained, despite the reduced myocardial shortening. Absolute wall thickening correlated with ejection fraction (R=0.70, P<.0001). In multiple linear regression analysis, increasing wall thickness by 1 mm independently increased ejection fraction by 3.43 percentage points (adjusted β‐coefficient: 3.43 [2.60–4.26], P<.0001). Increasing end‐diastolic wall thickness augments ejection fraction through preservation of absolute wall thickening. Left ventricular ejection fraction should not be used in patients with hypertensive heart disease without correction for degree of hypertrophy.

The relationship between left ventricular wall thickness, myocardial shortening and ejection fraction in hypertensive heart disease: insights from cardiac magnetic resonance: LVH independently augments EF in hypertension

Hypertensive heart disease is often associated with a preserved left ventricular ejection fraction despite impaired myocardial shortening. The authors investigated this paradox in 55 hypertensive patients (52±13 years, 58% male) and 32 age‐ and sex‐matched normotensive control patients (49±11 years, 56% male) who underwent cardiac magnetic resonance imaging at 1.5T. Long‐axis shortening (R=0.62), midwall fractional shortening (R=0.68), and radial strain (R=0.48) all decreased (P<.001) as end‐diastolic wall thickness increased. However, absolute wall thickening (defined as end‐systolic minus end‐diastolic wall thickness) was maintained, despite the reduced myocardial shortening. Absolute wall thickening correlated with ejection fraction (R=0.70, P<.0001). In multiple linear regression analysis, increasing wall thickness by 1 mm independently increased ejection fraction by 3.43 percentage points (adjusted β‐coefficient: 3.43 [2.60–4.26], P<.0001). Increasing end‐diastolic wall thickness augments ejection fraction through preservation of absolute wall thickening. Left ventricular ejection fraction should not be used in patients with hypertensive heart disease without correction for degree of hypertrophy.

Improving the poor diagnostic accuracy of the ECG at detecting prognostically significant left ventricular hypertrophy in hypertensive patients.

Background Normalised left ventricular mass (LVM) is a powerful prognostic tool. Traditionally, normalising has been achieved by indexing LVM to body surface area (BSA). A recent ‘Multiethnic Study of Atherosclerosis’ (MESA) sub-study demonstrated indexing LVM to height is more sensitive at identifying left ventricular hypertrophy (LVH) associated with cardiovascular events and all-cause death. We evaluated the ability of the ECG, an universal investigation in patients with hypertension, to detect LVH defined traditionally by LVM/BSA and by the prognostically more important LVM/height method using CMR (non-invasive gold-standard for LVM).