Native T1 and Extracellular Volume in Transthyretin Amyloidosis.

OBJECTIVES: This study evaluated the prognostic potential of native myocardial T1 in cardiac transthyretin amyloidosis (ATTR) and compared native T1 with extracellular volume (ECV) in terms of diagnostic accuracy and prognosis. BACKGROUND: ATTR is an increasingly recognized cause of heart failure that has an overlapping clinical phenotype with hypertrophic cardiomyopathy (HCM). Native T1 mapping by cardiac magnetic resonance (CMR) is useful for diagnosis in cardiac amyloidosis but its prognostic potential has never been assessed. METHODS: A total of 134 patients with wild-type ATTR (ATTRwt) (122 men; age 76 ± 7 years), 81 patients with hereditary-type ATTR (ATTRm) (60 men; age 69 ± 11 years), 44 patients with HCM (32 men; age 51 ± 13 years), and 12 asymptomatic mutation carriers (4 men; age 47 ± 10 years) were studied. All subjects underwent CMR with T1 mapping and ECV measurement. ATTR patients also underwent 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy. RESULTS: Native T1 and ECV were elevated in ATTR compared with HCM (p < 0.001) and were both associated with a high diagnostic accuracy (area under the curve [AUC]: 0.87; 95% confidence interval [CI]: 0.82 to 0.91) for T1 and an AUC of 0.91 (95% CI: 0.87 to 0.94) for ECV. No significant difference in native T1 and ECV was found between ATTRwt and ATTRm, and ECV correlated well with 99mTc-DPD scintigraphy. During follow-up of a mean of 32 ± 17 months, 55 ATTRwt and 40 ATTRm patients died. Native T1 and ECV predicted death (T1: hazard ratio [HR]: 1.225 for each 59-ms increase; 95% CI: 1.010 to 1.486; p < 0.05; ECV: HR: 1.155 for each 3% increase; 95% CI: 1.097 to 1.216; p < 0.001), but only ECV remained independently predictive after adjustment for age, N-terminal pro-B-type natriuretic peptide, left ventricular ejection fraction, E/E', left ventricular mass index, DPD grade, and late gadolinium enhancement. CONCLUSIONS: Native T1 mapping and ECV are good diagnostic techniques for cardiac ATTR that are associated with prognosis. Both parameters correlated with mortality, but only ECV remained independently predictive of prognosis, suggesting that it is a more robust marker in cardiac ATTR.

Prospective comparison of novel dark blood late gadolinium enhancement with conventional bright blood imaging for the detection of scar.

BACKGROUND: Conventional bright blood late gadolinium enhancement (bright blood LGE) imaging is a routine cardiovascular magnetic resonance (CMR) technique offering excellent contrast between areas of LGE and normal myocardium. However, contrast between LGE and blood is frequently poor. Dark blood LGE (DB LGE) employs an inversion recovery T2 preparation to suppress the blood pool, thereby increasing the contrast between the endocardium and blood. The objective of this study is to compare the diagnostic utility of a novel DB phase sensitive inversion recovery (PSIR) LGE CMR sequence to standard bright blood PSIR LGE. METHODS: One hundred seventy-two patients referred for clinical CMR were scanned. A full left ventricle short axis stack was performed using both techniques, varying which was performed first in a 1:1 ratio. Two experienced observers analyzed all bright blood LGE and DB LGE stacks, which were randomized and anonymized. A scoring system was devised to quantify the presence and extent of gadolinium enhancement and the confidence with which the diagnosis could be made. RESULTS: A total of 2752 LV segments were analyzed. There was very good inter-observer correlation for quantifying LGE. DB LGE analysis found 41.5% more segments that exhibited hyperenhancement in comparison to bright blood LGE (248/2752 segments (9.0%) positive for LGE with bright blood; 351/2752 segments (12.8%) positive for LGE with DB; p < 0.05). DB LGE also allowed observers to be more confident when diagnosing LGE (bright blood LGE high confidence in 154/248 regions (62.1%); DB LGE in 275/324 (84.9%) regions (p < 0.05)). Eighteen patients with no bright blood LGE were found to have had DB LGE, 15 of whom had no known history of myocardial infarction. CONCLUSIONS: DB LGE significantly increases LGE detection compared to standard bright blood LGE. It also increases observer confidence, particularly for subendocardial LGE, which may have important clinical implications.

Statins in Aortic Stenosis.

Calcific aortic stenosis (AS) is the most common form of valvular heart disease in Europe and North America. It is a progressive disease with a prolonged period of asymptomatic latency which eventually leads to critical left ventricular outflow tract obstruction necessitating surgical replacement of the valve. Statins are lipid-lowering drugs with a robust evidence base demonstrating clinical benefit in atherosclerotic coronary artery disease. There has therefore been significant interest in the potential benefit of statins in AS. Initial animal, retrospective and non-randomized prospective studies suggested a beneficial effect of statins in AS. However, the outcomes of 3 major randomized controlled clinical trials consistently failed to demonstrate any significant benefit of lipid-lowering therapy on progression or clinical outcomes in AS. Consequently, statin therapy should not be recommended if the sole purpose is prevention of AS progression and there is no other indication for lipid-lowering therapy. However, recent data have suggested that lipoprotein(a) (Lp(a)) may play a previously unknown but critical role in the progression of AS. Lp(a) is not significantly modified by statin therapy and there is therefore significant emerging interest in targeted reduction of Lp(a) with novel therapeutic agents such as PCSK9 inhibitors and antisense oligonucleotides.

The Impact of Antiplatelet Treatment on Endothelial Function.

The vascular endothelium comprises a continuous single cell layer of endothelial cells which line the entire cardiovascular system. Impaired endothelial function underlies the pathogenesis and contributes to the progression of atherosclerosis. Oxidative stress, vasoconstriction, inflammation, proliferation and thrombosis occur in dysfunctional endothelium while the latter, is primarily mediated by platelet activation and adherence to vascular wall. Despite the primary action of antiplatelet agents including aspirin, P2Y12 ADP receptor antagonists and glycoprotein IIb/IIIa inhibitors, a growing body of literature suggests that an important mechanism of their action involves complex modulation of endothelial function via platelet-endothelial interactions, modification of the inflammatory cytokine cascade and nitric oxide mediated effects. These agents represent the mainstay in pharmacological treatment of all aspects of cardiovascular disease both in primary and secondary prevention. However beyond these properties, it is important to note that pharmacological modification of endothelial dysfunction has been postulated as a therapeutic target for reduction of cardiovascular events.

Serum albumin changes and multivariate dynamic risk modelling in chronic heart failure.

BACKGROUND: We examined the prognostic utility of rate of change in serum albumin over time in chronic heart failure (CHF), as well as the utility of multivariate dynamic risk modelling. METHODS AND RESULTS: The survival implication of ∆albumin was analysed in 232 systolic CHF patients and validated in 212 patients. A multivariate dynamic risk score predicated on the rate of change in 6 simple indices including albumin was calculated and related to mortality. In derivation patients, 50 (22%) deaths occurred over 13 months. Greater rates of decline in albumin related to higher mortality (HR 0.55, 95% CI 0.41-0.73, P<0.0001) independently, incrementally and more accurately than other covariates including baseline albumin. A rate of attenuation >0.4 g/dL/month optimally forecasted death and was associated with a 5-fold escalated risk of mortality (HR 5.13, 95% CI 2.92-9.00, P<0.0001). Similar results were seen in the validation cohort. On multivariate dynamic risk modelling, survival at 1-year worsened with higher scores-a score ≥ 3 was associated with a 12-fold greater risk of death than a score of 0, a 6-fold higher risk of death than a score of 1, and a 4-fold enhanced risk of mortality than a score of 2. CONCLUSION: Attenuations in serum albumin over time relate to increased mortality in CHF, and a risk model predicated on the rate of change in 6 simple indices can identify patients at a 12-fold enhanced risk of death over the coming year.

Management dilemma in a paediatric patient with chronic gastric volvulus: a case report.

Gastric volvulus in children is rare. While the acute form is a surgical emergency, the chronic form may be managed either surgically or conservatively. The present report describes a premature (26+1 weeks) Afro-Caribbean neonate girl who presented with severe multiple bradycardias and apnoeas; she subsequently underwent pH monitoring and a barium study which demonstrated gastro-oesophageal reflux disease (GORD) and gastric volvulus. The patient represented a management dilemma as there were delays in establishing the diagnosis since medical treatment was started before pH monitoring was performed, and because of complications of prematurity precluding surgical treatment. This case supports an association between GORD and gastric volvulus while arguing that the mode of treatment should be based upon the severity of symptoms. This case is of particular interest to paediatricians who might consider this diagnosis in infants presenting with non-specific gastrointestinal and feeding problems particularly in association with GORD.