Matthew Lambert

Left Ventricular Noncompaction: Anatomical Phenotype or Distinct Cardiomyopathy?

Background There is considerable overlap between left ventricular noncompaction (LVNC) and other cardiomyopathies. LVNC has been reported in up to 40% of the general population, raising questions about whether it is a distinct pathological entity, a remodeling epiphenomenon, or merely an anatomical phenotype. Objectives The authors determined the prevalence and predictors of LVNC in a healthy population using 4 cardiac magnetic resonance imaging diagnostic criteria. Methods Volunteers >40 years of age (N = 1,651) with no history of cardiovascular disease (CVD), a 10-year risk of CVD < 20%, and a B-type natriuretic peptide level greater than their gender-specific median underwent magnetic resonance imaging scan as part of the TASCFORCE (Tayside Screening for Cardiac Events) study. LVNC ratios were measured on the horizontal and vertical long axis cine sequences. All individuals with a noncompaction ratio of ≥2 underwent short axis systolic and diastolic LVNC ratio measurements, and quantification of noncompacted and compacted myocardial mass ratios. Those who met all 4 criteria were considered to have LVNC. Results Of 1,480 participants analyzed, 219 (14.8%) met ≥1 diagnostic criterion for LVNC, 117 (7.9%) met 2 criteria, 63 (4.3%) met 3 criteria, and 19 (1.3%) met all 4 diagnostic criteria. There was no difference in demographic or allometric measures between those with and without LVNC. Long axis noncompaction ratios were the least specific, with current diagnostic criteria positive in 219 (14.8%), whereas the noncompacted to compacted myocardial mass ratio was the most specific, only being met in 61 (4.4%). Conclusions A significant proportion of an asymptomatic population free from CVD satisfy all currently used cardiac magnetic resonance imaging diagnostic criteria for LVNC, suggesting that those criteria have poor specificity for LVNC, or that LVNC is an anatomical phenotype rather than a distinct cardiomyopathy.

Medical management of critical limb ischaemia: where do we stand today?

Critical limb ischaemia (CLI) is a severe form of peripheral arterial disease (PAD). CLI often causes disabling symptoms of pain and can lead to loss of the affected limb. It is also associated with increased risk of myocardial infarction, stroke and death from cardiovascular disease. The aims of management in patients with CLI are to relieve ischaemic pain, heal ulcers, prevent limb loss, improve function and quality of life and prolong survival. Here, current evidence regarding the medical management of CLI is reviewed. Cardiovascular risk factors should be assessed in all patients with CLI; smoking cessation and treatment of hypertension, hyperlipidaemia and diabetes all reduce the mortality rate in those with PAD. Antiplatelet agents (either aspirin or clopidogrel) are recommended to reduce both the incidence of cardiovascular events and risk of arterial occlusion. By contrast, routine use of anticoagulation (either warfarin or heparin) is not recommended. Treatment of the limbs themselves is often more challenging. Prostanoids may have some efficacy for treating rest pain and for ulcer healing, and iloprost shows favourable results in reducing the risk of major amputations, but long‐term follow‐up data regarding disease progression are lacking. There is insufficient evidence to support the use of naftidrofuryl or cilostazol, and pentoxifylline is not beneficial. Furthermore, there is no evidence of proven benefit of hyperbaric oxygen. A number of angiogenic growth factors have been studied in Phase I studies and randomized controlled trials (RCTs). They appear to be safe, but efficacy results have been mixed. Treatment with stem cells also shows some potential from early trials, but further larger RCTs are needed to demonstrate clear benefit. Thrombolysis may be an alternative for patients who develop acute limb ischaemia and are unsuitable for surgical intervention. However, newer endovascular techniques are likely to have a greater role in the future.

Common carotid intima media thickness and ankle-brachial pressure index correlate with local but not global atheroma burden: a cross sectional study using whole body magnetic resonance angiography.

Background Common carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA). Methods 50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0 = normal, 1 = <50%, 2 = 50–70%, 3 = 70–99%, 4 = vessel occlusion. The segment scores were summed and from this a standardized atheroma score was calculated. Results The atherosclerotic burden was high with a standardised atheroma score of 39.5±11. Common CIMT showed a positive correlation with the whole body atheroma score (β 0.32, p = 0.045), however this was due to its strong correlation with the neck and thoracic segments (β 0.42 p = 0.01) with no correlation with the rest of the body. ABPI correlated with the whole body atheroma score (β −0.39, p = 0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global atheroma burden was present (β 0.13 p = 0.45), while the correlation between ABPI and atheroma burden persisted (β −0.45 p = 0.005). Conclusion ABPI but not CIMT correlates with global atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral atheroma burden.

Technical assessment of whole body angiography and cardiac function within a single MRI examination

Aim To evaluate a combined protocol for simultaneous cardiac MRI (CMR) and contrast-enhanced (CE) whole-body MR angiography (WB-MRA) techniques within a single examination. Materials and methods Asymptomatic volunteers (n = 48) with low-moderate risk of cardiovascular disease (CVD) were recruited. The protocol was divided into four sections: (1) CMR of left ventricle (LV) structure and function; (2) CE-MRA of the head, neck, and thorax followed by the distal lower limbs; (3) CMR LV “late gadolinium enhancement” assessment; and (4) CE-MRA of the abdomen and pelvis followed by the proximal lower limbs. Multiple observers undertook the image analysis. Results For CMR, the mean ejection fraction (EF) was 67.3 ± 4.8% and mean left ventricular mass (LVM) was 100.3 ± 22.8 g. The intra-observer repeatability for EF ranged from 2.1–4.7% and from 9–12 g for LVM. Interobserver repeatability was 8.1% for EF and 19.1 g for LVM. No LV delayed myocardial enhancement was observed. For WB-MRA, some degree of luminal narrowing or stenosis was seen at 3.6% of the vessel segments (involving n = 29 of 48 volunteers) and interobserver radiological opinion was consistent in 96.7% of 1488 vessel segments assessed. Conclusion Combined assessment of WB-MRA and CMR can be undertaken within a single examination on a clinical MRI system. The associated analysis techniques are repeatable and may be suitable for larger-scale cardiovascular MRI studies.

Prevalence of unrecognized myocardial infarction in a low-intermediate risk asymptomatic cohort and its relation to systemic atherosclerosis

Aims Unrecognized myocardial infarctions (UMIs) have been described in 19–30% of the general population using late gadolinium enhancement (LGE) on cardiac magnetic resonance. However, these studies have focused on an unselected cohort including those with known cardiovascular disease (CVD). The aim of the current study was to ascertain the prevalence of UMIs in a non-high-risk population using magnetic resonance imaging (MRI). Methods and results A total of 5000 volunteers aged >40 years with no history of CVD and a 10-year risk of CVD of <20%, as assessed by the ATP-III risk score, were recruited to the Tayside Screening for Cardiac Events study. Those with a B-type natriuretic peptide (BNP) level greater than their gender-specific median were invited for a whole-body MR angiogram and cardiac MR including LGE assessment. LGE was classed as absent, UMI, or non-specific. A total of 1529 volunteers completed the imaging study; of these, 53 (3.6%) were excluded because of either missing data or inadequate LGE image quality. Ten of the remaining 1476 (0.67%) displayed LGE. Of these, three (0.2%) were consistent with UMI, whereas seven were non-specific occurring in the mid-myocardium (n = 4), epicardium (n = 1), or right ventricular insertion points (n = 2). Those with UMI had a significantly higher BNP [median 116 (range 31–133) vs. 22.6 (5–175) pg/mL, P = 0.015], lower ejection fraction [54.6 (36–62) vs. 68.9 (38–89)%, P = 0.007], and larger end-systolic volume [36.3 (27–61) vs. 21.7 (5–65) mL/m2, P = 0.014]. Those with non-specific LGE had lower diastolic blood pressure [68 (54–70) vs. 72 (46–98) mmHg, P = 0.013] but no differences in their cardiac function. Conclusion Despite previous reports describing high prevalence of UMI in older populations, in a predominantly middle-aged cohort, those who are of intermediate or low cardiovascular risk have a very low risk of having an unrecognized myocardial infarct.

3T MRI investigation of cardiac left ventricular structure and function in a UK population: The tayside screening for the prevention of cardiac events (TASCFORCE) study

To scan a volunteer population using 3.0T magnetic resonance imaging (MRI). MRI of the left ventricular (LV) structure and function in healthy volunteers has been reported extensively at 1.5T.

Whole-body cardiovascular MRI for the comparison of atherosclerotic burden and cardiac remodelling in healthy South Asian and European adults.

Objective: To determine the feasibility of using whole-body cardiovascular MRI (WB-CVMR) to compare South Asians (SAs)—a population known to have a higher risk of cardiovascular disease (CVD) but paradoxically lower prevalence of peripheral arterial disease—and Western Europeans (WEs). Methods: 19 SAs and 38 age-, gender- and body mass index-matched WEs were recruited. All were aged 40 years and over, free from CVD and with a 10-year risk of CVD <20% as assessed by the adult treatment panel (ATP) III risk score. WB-CVMR was performed, comprising a whole-body angiogram (WBA) and cardiac MR (CMR), on a 3-T MRI scanner (Magnetom® Trio; Siemens, Erlangen, Germany) following dual-phase injection of gadolinium-based contrast agent. A standardized atheroma score (SAS) was calculated from the WBA while indexed left ventricular mass and volumes were calculated from the CMR. Results: SAs exhibited a significantly lower iliofemoral atheroma burden (regional SAS 0.0 ± 0.0 vs 1.9 ± 6.9, p = 0.048) and a trend towards lower overall atheroma burden (whole-body SAS 0.7 ± 0.8 vs 1.8 ± 2.3, p = 0.1). They had significantly lower indexed left ventricular mass (46.9 ± 11.8 vs 56.9 ± 13.4 ml m−2, p = 0.008), end diastolic volume (63.9 ± 10.4 vs 75.2 ± 11.4 ml m−2, p=0.001), end systolic volume (20.5 ± 6.1 vs 24.6 ± 6.8 ml m−2, p = 0.03) and stroke volume (43.4 ± 6.6 vs 50.6 ± 7.9 ml m−2, p = 0.001), but with no significant difference in ejection fraction, mass-volume ratio or global functioning index. These differences persisted after accounting for CVD risk factors. Conclusion: WB-CVMR can quantify cardiac and atheroma burden and can detect differences in these metrics between ethnic groups that, if validated, may suggest that the paradoxical high risk of CVD compared with PVD risk may be due to an adverse cardiac haemodynamic status incurred by the smaller heart rather than atherosclerosis. Advances in knowledge: WB-CVMR can be used to stratify and compare disease between ethnicities.

Prevalence and Distribution of Atherosclerosis in a Low- to Intermediate-Risk Population: Assessment with Whole-Body MR Angiography

Purpose To quantify the burden and distribution of asymptomatic atherosclerosis in a population with a low to intermediate risk of cardiovascular disease. Materials and Methods Between June 2008 and February 2013, 1528 participants with 10-year risk of cardiovascular disease less than 20% were prospectively enrolled. They underwent whole-body magnetic resonance (MR) angiography at 3.0 T by using a two-injection, four-station acquisition technique. Thirty-one arterial segments were scored according to maximum stenosis. Scores were summed and normalized for the number of assessable arterial segments to provide a standardized atheroma score (SAS). Multiple linear regression was performed to assess effects of risk factors on atheroma burden. Results A total of 1513 participants (577 [37.9%] men; median age, 53.5 years; range, 40-83 years) completed the study protocol. Among 46 903 potentially analyzable segments, 46 601 (99.4%) were interpretable. Among these, 2468 segments (5%) demonstrated stenoses, of which 1649 (3.5%) showed stenosis less than 50% and 484 (1.0%) showed stenosis greater than or equal to 50%. Vascular stenoses were distributed throughout the body with no localized distribution. Seven hundred forty-seven (49.4%) participants had at least one stenotic vessel, and 408 (27.0%) participants had multiple stenotic vessels. At multivariable linear regression, SAS correlated with age (B = 3.4; 95% confidence interval: 2.61, 4.20), heart rate (B = 1.23; 95% confidence interval: 0.51, 1.95), systolic blood pressure (B = 0.02; 95% confidence interval: 0.01, 0.03), smoking status (B = 0.79; 95% confidence interval: 0.44, 1.15), and socioeconomic status (B = -0.06; 95% confidence interval: -0.10, -0.02) (P < .01 for all). Conclusion Whole-body MR angiography identifies early vascular disease at a population level. Although disease prevalence is low on a per-vessel level, vascular disease is common on a per-participant level, even in this low- to intermediate-risk cohort.

Reply: The Enigma of Left Ventricular Non-Compaction

We thank Drs. Stollberger and Finsterer for their interest in our paper on left ventricular noncompaction (LVNC) in which we report that a significant proportion of an asymptomatic healthy population meet current diagnostic criteria [(1)][1]. As they quite rightly state cardiac magnetic resonance

15 No association between systemic arteriosclerosis and atherosclerosis on cardiac MRI and whole body angiography: the tascforce study

Introduction Arteriosclerosis (arterial stiffening) and atherosclerosis (plaque formation) are pathophysiological processes afflicting the vasculature, both of which are associated with future cardiovascular events. However the degree to which they overlap or simply co-exist is poorly understood. The aim of the current study is to determine if these two processes are significantly associated with one another. Methods 1651 volunteers with no clinical manifestation of cardiovascular disease and <20% 10-year cardiovascular risk underwent a cardiac MRI and whole body MR angiogram as part of the TASCFORCE study. Systemic arterial stiffness was measured using total arterial compliance (TAC) – calculated as the indexed stroke volume divided by the pulse pressure. Systemic atheroma burden (AB) was calculated by scoring 30 arterial segments within the body based on the degree of stenosis, summating these scores and normalising it to the number of assessable segments. Results 1515 (574 male, 53.8±8.2 years-old) completed the study.?On multiple linear regression age (B=–0.001 (95%CI –?0.002–−0.000), p=0.004), heart rate (B=–0.003 (95%CI –?0.003–−0.002), p<0.001) and blood pressure (B=–0.008 (95%CI –0.009–−0.008), p<0.001) were independently associated with TAC, while age (B=0.061 (95%CI 0.04–0.08), p<0.001), and smoking pack-year history (B=0.003 (95%CI 0.005), p=0.022) were independently associated with AB. TAC and AB?demonstrated a significant correlation with each other (Spearman rho=–0.12, p<0.001), however on multivariable analysis accounting for age, blood pressure, sex, BMI, smoking status and cholesterol no significant association persisted (B=–?0.001 (95%CI –0.004–0.002), p=0.62). Conclusion Systemic arteriosclerosis and atherosclerosis are separate entities with each determined by different risk factors. Future efforts in cardiovascular risk prevention should seek to address both of these pathophysiological entities.