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Introduction: Determination of blood volume, red cell volume, and plasma volume contributes to the understanding of the pathophysiology in heart failure, especially concerning anemia and volume load. The optimized carbon monoxide (CO)-rebreathing method (oCORM) is used to determine these parameters and hemoglobin mass (Hbmass) in exercise physiology. The applicability of oCORM to determine the intravascular volumes and Hbmass in heart failure patients is currently undetermined because assumptions concerning CO kinetics with oCORM rely on healthy subjects with a normal ejection fraction. Therefore, the aim of the present study is to determine the applicability and the systematic error of oCORM arising from a reduced EF when oCORM is used for measurement of intravascular volumes and Hbmass in heart failure patients.Methods: oCORM was performed in 21 patients with heart failure and a reduced ejection fraction (EF) of < 30% (EFsev) and 25 controls (CONT). CO kinetics in capillary blood was studied 3–15 min after commencement of CO rebreathing. Differences in CO kinetics between the groups were assessed using a generalized linear model. The systematic error for determination of Hbmass with oCORM arising from differences in CO kinetics was assessed using the Monte Carlo method.Results: The CO kinetics was significantly different between EFsev and CONT. In both groups, exposure to CO led to a COHb increase to 6.0 ± 1.0% 3 min after CO rebreathing. There were no CO related side effects or any clinical symptoms. Monte Carlo simulation quantifies the systematic error for determination of Hbmass arising from an impaired ejection fraction to be −0.88%.Conclusion: Our results indicate an impaired vascular mixing of CO when EF is severely reduced. When Hbmass is determined using the original oCORM protocol in heart failure patients with a reduced EF, the systematic underestimation of about 1% should be considered. However, the error arising from this impaired vascular mixing appears small and clinically negligible. Furthermore, application of oCORM was safe and not related to any side effects resulting from CO exposure. In conclusion, oCORM can be used for assessing intravascular volumes and Hbmass in patients with a reduced EF.

Background The point mutation at position 3243 in the mitochondrial MT-TL1 gene (m.3243A &gt; G) is a rare cause of hypertrophic cardiomyopathy (HCM). Information about HCM progression over time and occurrence of different cardiomyopathies in m.3243A &gt; G carriers of the same family is still lacking. Case summary A 48-year old male patient was admitted to a tertiary care hospital with chest pain and dyspnea. Bilateral hearing loss required hearing aids at the age of 40. A short PQ interval, narrow QRS complex and inverted T-waves in lateral leads were present on electrocardiogram. HbA1c of 7.3 mmol/L indicated prediabetes. Echocardiography excluded valvular heart disease and detected non-obstructive hypertrophic cardiomyopathy with slightly reduced left ventricular ejection fraction (LVEF 48%). Coronary artery disease was ruled out by coronary angiography. Myocardial fibrosis determined by repeated cardiac MRI progressed over time. Endomyocardial biopsy excluded storage disease, Fabry disease, infiltrative and inflammatory cardiac disease. Genetic testing revealed m.3243A &gt; G mutation in the MT-TL1 gene associated with mitochondrial disease. Clinical evaluation and genetic testing of the patients’ family revealed five genotype-positive relatives with heterogeneous clinical phenotypes including deafness, diabetes mellitus, kidney disease and both hypertrophic and dilated cardiomyopathy. Discussion In patients with unexplained symmetric HCM with heterogenic clinical phenotypes at the organ levels mitochondrial disease should be taken into consideration, particularly in the context of matrilinear transmission. m.3243A &gt; G mutation is associated with a mitochondrial disease in the index patient and five family members and leads to the diagnosis of maternal inherited diabetes and deafness (MIDD) with intra-familial variability of different cardiomyopathy forms.