Piia Simonen

BACKGROUND: Cardiac sarcoidosis involves a significant but difficult-to-define risk of sudden cardiac death (SCD). Current guidelines recommend consideration of an implantable cardioverter defibrillator for patients with extensive or significant myocardial late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging. However, extensive/significant LGE is not defined. METHODS: A nationwide cardiac sarcoidosis registry was screened for patients entered before 2020 with cardiac magnetic resonance imaging done before or P <0.001), with receiver operating characteristic analyses identifying LGE mass ≥9.9% and ≥6 LGE segments as discriminative thresholds. At presentation, 70 patients were free of class I and class IIa implantable cardioverter defibrillator indications unrelated to LGE. Their 5-year rate of SCD/VT was 6.3% (0.0–14.8%) with LGE mass <9.9% versus 21.5% (6.5–36.6%) with higher LGE mass, and 6.9% (0.0–16.3%) with <6 LGE segments versus 20.5% (5.9–35.2%) with ≥6 segments. CONCLUSIONS: In cardiac sarcoidosis, myocardial LGE making up ≥9.9% of LV mass or affecting ≥6 LV segments may suggest prognostically significant LV involvement and a high risk of SCD. However, prospective validation of the thresholds is needed.

Background: Small intestinal neuroendocrine tumors (SI-NETs) are characterized by carcinoid syndrome and carcinoid heart disease (CHD). The aim of the present study was to identify early risk markers for carcinoid heart disease and survival in a prospective median-term follow-up setting. Methods: We measured 5-HIAA and cumulative 5-HIAA exposure (Cum-5-HIAA) based on repeated measurements, proBNP, vascular function, hepatic tumor load, and transthoracic echocardiography (TTE) at baseline and during the median 5-year follow-up. Of 65 patients with SI-NETs, 54 patients underwent a prospective follow-up. In addition, survival was evaluated during the median follow-up of 6 years. Results: At baseline, three patients had CHD. During the median follow-up of 5 years, two patients (4%) developed CHD. Cum-5-HIAA and proBNP correlated with CHD (Westberg score, Spearman’s ρ = 0.32 and 0.31, respectively). Cum-5-HIAA had a superior diagnostic capability, predicting CHD in receiver operator characteristic analysis with an AUC of 0.98 (95% CI: 0.94–1.00) and outperformed proBNP, chromogranin A (CgA), and individual serum 5-HIAA measurements (AUC = 0.75, 0.85, and 0.91, respectively). Minor changes in valve regurgitation were frequently detected but did not correlate with vascular function. Regurgitation increased or decreased in 29% of tricuspid and 30% of pulmonic valves. CHD, hepatic tumor load, serum 5-HIAA, and elevated aortic pulse wave velocity (PWV) were associated with increased mortality in SI-NET patients. Conclusions: Cum-5-HIAA is a promising biomarker for CHD risk and outperformed other biomarkers. CHD and hepatic tumor load are the strongest predictors of mortality. PWV is a novel predictor of survival. The incidence of CHD was low among the SI-NET patients, probably reflecting successful treatment regimens.

Background Small intestinal neuroendocrine tumors (SI-NETs) are characterized by carcinoid syndrome and carcinoid heart disease (CHD). The aim of study was to identify early risk markers for carcinoid heart disease and survival in a prospective median-term follow-up setting. Methods We measured 5-HIAA, cumulative 5-HIAA exposure (Cum-5-HIAA) based on repeat measurements, proBNP, vascular function, hepatic tumor load and transthoracic echocardiography (TTE) were assessed at baseline and during median 5-year follow-up. Of 65 patients with SI-NETs; 54 patients underwent prospective follow-up. In addition, survival was evaluated during median follow-up of 6 years. Results At baseline three patients had CHD. During median follow-up of 5 years, two patients (4%) developed CHD. Cum-5-HIAA and proBNP correlated with CHD (Westberg Score, Spearman’s ρ = 0.32 and 0.31, respectively). Cum-5-HIAA had a superior diagnostic capability, predicting CHD in receiver operator characteristics analysis with AUC of 0.98 (95% CI: 0.94–1.00) and outperformed proBNP, chromogranin A (CgA), as well as individual serum 5-HIAA measurements (AUC = 0.75, 0.85, and 0.91, respectively). Minor changes in valve regurgitation were frequently detected but did not correlate with vascular function. In 29% of tricuspid and 30% of pulmonic valves regurgitation increased or decreased. CHD, hepatic tumor load, serum 5-HIAA, and elevated aortic pulse wave velocity (PWV) associated with increased mortality in SI-NET patients. Conclusions Cum-5-HIAA is a promising biomarker for CHD risk and outperformed other biomarkers. CHD and hepatic tumor load are strongest predictors of mortality. PWV is a novel predictor of survival. The incidence of CHD was small among the SI-NET patients, probably reflecting successful treatment regimens.

Dietary modifications including plant stanol ester consumption are recommended measures to control serum and low-density lipoprotein (LDL)-cholesterol concentrations, but obesity can affect their responses. We investigated whether body mass index (BMI) affects serum cholesterol levels during plant stanol (mainly sitostanol) ester consumption. This ad hoc analysis was based on earlier results of a cross-over, randomized controlled trial of postmenopausal women consuming rapeseed oil-based margarine without or with plant stanol ester (3 g plant stanols/day) for seven weeks. We classified the subjects as normal-weight (BMI ≤ 25 kg/m², n = 9, mean 22.6 kg/m²) or overweight/obese (BMI > 25 kg/m², n = 11, mean 28.4 kg/m²), and recalculated the results, focusing on cholesterol absorption, cholesterol synthesis, and fecal steroid outputs. Serum cholesterol levels were similar in the groups during the control diet. Plant stanol ester reduced serum cholesterol by 0.63 ± 0.19 mmol/L (11%) in normal-weight and by 0.75 ± 0.13 mmol/L (12%) in overweight/obese subjects (p < 0.05 for both), and cholesterol absorption was reduced in both groups. However, relative and dietary cholesterol absorption were more effectively reduced in normal-weight subjects. In conclusion, overweight/obesity did not interfere with the serum cholesterol response to plant stanol ester consumption despite substantial differences in cholesterol metabolism between the groups.

Atherosclerotic cardiovascular diseases (ASCVDs) cause every fifth death worldwide. However, it is possible to prevent the progression of ASCVDs by reducing circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Recent large meta-analyses demonstrated that by reducing the dietary intake of saturated fat and cholesterol, it is possible to reduce the risk of ASCVD events. Plant stanols, as fatty-acid esters, were developed as a dietary adjunct to reduce LDL-C levels as part of a heart-healthy diet. They reduce cholesterol absorption so that less cholesterol is transported to the liver, and the expression of LDL receptors is upregulated. Ultimately, LDL-C concentrations are reduced on average by 9–12% by consuming 2–3 g of plant stanol esters per day. In this review, we discuss recent information regarding the prevention of ASCVDs with a focus on dietary means. We also present new estimates on the effect of plant stanol ester consumption on LDL-C levels and the risk of ASCVD events. Plant stanol esters as part of a heart-healthy diet plausibly offer a means to reduce the risk of ASCVD events at a population level. This approach is not only appropriate for subjects with a high risk of ASCVD, but also for subjects at an apparently lower risk to prevent subclinical atherosclerosis.