Phospholamban cardiomyopathy: a Canadian perspective on a unique population

Introduction

Phospholamban cardiomyopathy is an inherited cardiomyopathy, characterised by a defect in regulation of the sarcoplasmic reticulum Ca²⁺ pump, often presenting with malignant arrhythmias and progressive cardiac dysfunction occurring at a young age.

Methods

Phospholamban R14del mutation carriers and family members were identified from inherited arrhythmia clinics at 13 sites across Canada. Cardiac investigations, including electrocardiograms, Holter monitoring (premature ventricular complexes, PVCs), and imaging results were summarised.

Results

Fifty patients (10 families) were identified (median age 30 years, range 3–71, 46% female). Mutation carriers were more likely to be older, have low-voltage QRS, T‑wave inversion, frequent PVCs, and cardiac dysfunction, compared to unaffected relatives. Increasing age, low-voltage QRS, T‑wave inversion, late potentials, and frequent PVCs were predictors of cardiac dysfunction (p < 0.05 for all). Older carriers (age ≥45 years) were more likely to have disease manifestations than were their younger counterparts, with disease onset occurring at an older age in Canadian patients and their Dutch counterparts.

Discussion

Among Canadian patients with phospholamban cardiomyopathy, clinical manifestations resembled those of their Dutch counterparts, with increasing age a major predictor of disease manifestation. Older mutation carriers were more likely to have electrical and structural abnormalities, and may represent variable expressivity, age-dependent penetrance, or genetic heterogeneity among Canadian patients.

     

Ichnological evidence of a Miocene rhinoceros bitten by a bear-dog (Amphicyon giganteus)

A rhinocerotid hemimandible, the Iberotherium rexmanueli zbyszewskii holotype, was bitten by Amphicyon giganteus, a carnivore that could attack large prey and be an opportunistic scavenger as well. The large, young adult Iberotherium was not senile and may have been killed by a single individual or by a pack of Amphicyon giganteus, but disease or accident may also have caused its death. Alternatively, during a drought event, a dying or in harsh physical condition rhinoceros may have been overcome while seeking a water point where ambush would be possible. Death also may have been a consequence of a major flood. As decay progressed and the remnants were eventually deposited, parts could have been consumed by scavengers. After consumption, wet bone surfaces could undergo some corrosion. Fissures may have resulted from desiccation or mechanical stress. The hemimandible was abandoned after consumption and left exposed until new sands were deposited over it.     

A routine intervention in a highly unusual vessel

Netherlands Heart Journal -     

Invasive coronary physiology: a Dutch tradition

Invasive coronary physiology has been applied since the early days of percutaneous transluminal coronary angioplasty, and has become a rapidly emerging field of research. Many physiology indices have been developed, tested in clinical studies, and are now applied in daily clinical practice. Recent clinical practice guidelines further support the use of advanced invasive physiology methods to optimise the diagnosis and treatment of patients with acute and chronic coronary syndromes. This article provides a succinct review of the history of invasive coronary physiology, the basic concepts of currently available physiological parameters, and will particularly highlight the Dutch contribution to this field of invasive coronary physiology.

     

Cardiogenetics, 25 years a growing subspecialism

The cardiology and clinical genetics subspecialty of cardiogenetics has experienced a tremendous growth in the past 25 years. This review discusses examples of the progress that has been made as well as new challenges that have arisen within this field, with special focus on the Netherlands. A significant number of Dutch founder mutations, i.e. mutations shared by a number of individuals who have a common origin and all share a unique chromosomal background on which the mutation occurred, have been identified and have provided unique insights into genotype-phenotype correlations in inherited arrhythmia syndromes and inherited cardiomyopathies.

Cardiological and genetic screening of family members of young victims of sudden cardiac death combined with genetic testing in the deceased individual have turned out to be rewarding. However, the interpretation of the results of genetic testing in this setting and in the setting of living patients with a (suspected) phenotype is now considered more challenging than previously anticipated, because the introduction of high-throughput sequencing technologies has resulted in the identification of a significant number of variants of unknown significance. Interpretation of genetic and clinical findings by experienced multidisciplinary teams are key to ensure a high quality of care to the patient and the family.

     

Right coronary artery supply to a cardiac mass

Netherlands Heart Journal -     

ST-segment elevation in a patient with cardiac lymphoma

Netherlands Heart Journal -     

Mobile health: solution or a threat?

Netherlands Heart Journal -     

Coronary physiology assessment in a cardiac transplant patient

Netherlands Heart Journal -     

Evidence for the longest stratigraphic range of a post-Triassic Ichthyosaur: a Leptonectes tenuirostris from the Pliensbachian (Lower Jurassic) of Switzerland

A three-dimensional well-preserved ichthyosaur skull and parts of the postcranial skeleton are attributed to the species Leptonectes tenuirostris (Conybeare, 1822). It was found vertically embedded in Pliensbachian deposits representing three successive biozones (ibex to margaritatus Zone). The find is dated as early Late Pliensbachian (margaritatus Zone) by a rich ammonite and ostracod fauna. It is the first record of the genus Leptonectes from Switzerland and from the Late Pliensbachian. It is so far the best preserved and most complete ichthyosaur from this time interval worldwide. With diagnostic specimens known from the Rhaetian (Late Keuper) up to the early Late Pliensbachian (Middle Liassic), L. tenuirostris (Conybeare, 1822) has the most extensive stratigraphic range documented for any post-Triassic ichthyosaur so far.     

Strong inhibition of peptide amyloid formation by a fatty acid

The aggregation of peptides into amyloid fibrils is associated with several diseases, including Alzheimer’s and Parkinson’s disease. Because hydrophobic interactions often play an important role in amyloid formation, the presence of various hydrophobic or amphiphilic molecules, such as lipids, may influence the aggregation process. We have studied the effect of a fatty acid, linoleic acid, on the fibrillation process of the amyloid-forming model peptide NACore (GAVVTGVTAVA). NACore is a peptide fragment spanning residue 68–78 of the protein α-synuclein involved in Parkinson’s disease. Based primarily on circular dichroism measurements, we found that even a very small amount of linoleic acid can substantially inhibit the fibrillation of NACore. This inhibitory effect manifests itself through a prolongation of the lag phase of the peptide fibrillation. The effect is greatest when the fatty acid is present from the beginning of the process together with the monomeric peptide. Cryogenic transmission electron microscopy revealed the presence of nonfibrillar clusters among NACore fibrils formed in the presence of linoleic acid. We argue that the observed inhibitory effect on fibrillation is due to co-association of peptide oligomers and fatty acid aggregates at the early stage of the process. An important aspect of this mechanism is that it is nonmonomeric peptide structures that associate with the fatty acid aggregates. Similar mechanisms of action could be relevant in amyloid formation occurring in vivo, where the aggregation takes place in a lipid-rich environment.     

Pleistocene fish otoliths from the Mediterranean Basin: a synthesis

An overview of upper pPliocene and pleistocene otolith assemblages is compiled on the basis of both literature data and newly collected material from several sections located mainly in southern Italy. One hundred and five taxa are listed. Additional comments are provided for taxa subject to discussion. The composition and affinities of the Mediterranean Pleistocene otolith associations (consisting mainly of deep sea fishes) is checked against the available data for Pre-Messinian, Pliocene, and Recent Mediterranean fishes. This analysis is based on the recorded nominal species, but some taxa that could be identified at the generic level only are also included when they are relevant from a biogeographic point of view. Some new data on Piacenzian (middle Pliocene) and Gelasian (upper Pliocene) otoliths are also provided because this time interval still constitutes a major gap in the knowledge of the stratigraphic range of Plio-Pleistocene fish taxa. The Pleistocene deepwater fish fauna of the Mediterranean shows a markedly more oceanic character than the present-day one, a tendency that was all ready observed from early Oligocene till Pliocene times. Starting from the late Piacenzian, an increasing number of Atlantic taxa progressively invaded the Mediterranean including several subpolar and temperate forms. This invasion became stronger in the Gelasian. From this period up to the middle and late Pleistocene, the Mediterranean deepwater fish fauna (mesopelagic and benthopelagic) is enriched by taxa which today are typical for the north Atlantic cold deep water. This faunal shift seems to be correlated with the evolution of the Plio-Pleistocene Mediterranean paleoceanographic setting as well as with the global climatic deterioration.