Sean Coffey

Why is additional monitoring needed? ESC/EACTS guidelines recommend reassessment every 6 months,1 hardly a level of frequency that would be viewed as excessive. However, as always when theory meets practice, practice wins out, and even in better resourced settings than the United Kingdom’s National Health Service, adherence to reassessment timeframes is seen in only around half of patients with severe AS.3 …

Background: Semantic differential scales, in which respondents rate their relative agreement between two opposing statements, are rarely used in assessment of health related quality of life (QOL). Here we present a use-case study describing our experiences constructing such a scale, part of a larger project to generate a questionnaire, the VALVQ, to measure QOL in heart valve disease (HVD). Methods and results: Individuals with HVD were identified from echocardiographic databases. Initial questionnaire content was generated from semi-structured interviews with 34 individuals with HVD as well as three family members and five clinical experts. Four methods were used to generate semantic differential items. Firstly, two participants could give opposing points, allowing an item to be generated directly. Secondly, a participant could report a single experience at one extreme, with the research team generating the opposing statement. Thirdly, a participant could report an experience in the middle of two extremes, with two opposing statement generated by the research team. Finally, subtly different items were generated where an obvious corresponding item was not clear, allowing for future psychometric testing to examine item robustness. 64 semantic differential items were generated for pilot testing. 46 valid completed questionnaires were returned. Multiple items required changes due to phrasing of the item content, but no difficulties were reported with the semantic differential format. Conclusion: The semantic differential scale can be considered for health related QOL research. Further head-to-head comparisons with the more common Likert format will allow assessment of differences in respondent biases between these questionnaire formats.

Patients with ischaemic heart disease (IHD) require frequent monitoring, as the transition from stable disease to acute life-threatening events remains largely unpredictable. MicroRNAs (miRNAs), small non-coding RNAs involved in physiological and pathological processes, are released into circulation and remain stable. In this study, we aimed to determine if the serial measurement of cardiovascular-enriched circulating miRNAs could reflect changes in cardiac function in patients with IHD. Fifty-three new IHD patients participated in a five-year study with regular echocardiography, blood tests and follow-ups at 12-month intervals, with 25 followed up at five years. Serial echocardiography revealed a pattern towards worsening diastolic function over the follow-up period. RT-PCR analysis was conducted on four cardiovascular-enriched circulating miRNAs: miR-1, miR-126, miR-132 and miR-34a. Among these, only miR-1 and miR-126 showed statistically significant down-regulation starting from 24 months onwards. Linear mixed models, adjusted for body mass index and HbA1c changes, indicated significant associations between fold changes in miR-1 and miR-34a with cardiac function changes. Results from this first-ever five-year follow-up study have identified a possible link between cardiovascular-enriched miRNAs, miR-1 and -34a and cardiac function in patients with IHD, providing a foundation for prognostic tests for IHD and laying the foundation for further studies in larger populations. It is noteworthy that a significant dropout of participants may have impacted the statistical power in our study.

Background: Cardiac radiopharmaceutical uptake during bone scintigraphy is a specific finding of cardiac amyloidosis, particularly transthyretin amyloid. There is little evidence to guide the optimum choice of technetium labelled radiopharmaceutical in protocols to detect cardiac amyloid. In our practice, different radiopharmaceuticals were used based on external factors such as availability and pricing. We wished to use this natural experiment to examine the rate of incidental cardiac uptake in clinically indicated bone scintigraphy. Methods: Bone scintigraphy for non-cardiac indications was examined over a three-year period. Radiopharmaceutical and demographic data were recorded, and scans were evaluated retrospectively using the Perugini scale. Results: One thousand four hundred seventy-three scans were examined, and of these, the radiopharmaceutical used was: 209 DPD, 175 HDP, 51 HMDP, and 1038 MDP. There were no significant differences between radiopharmaceutical groups regarding patient demographics or indications for imaging. The rate of radiopharmaceutical cardiac uptake (Perugini grade >1) was 2.4% for DPD, 0% HDP, 0% HMDP, and 0.3% MDP (Fisher exact test p=0.011). Conclusions: DPD may confer higher sensitivity than other radiopharmaceuticals to diagnose cardiac amyloid. These results encourage a direct comparison of radiopharmaceuticals to detect cardiac amyloid.

Background: The differential DNA methylation (DNAm) of the CpG site cg05575921, within the gene body of AHRR, has been shown to be a robust indicator of tobacco smoking exposure. This study aimed to determine if cg05575921 at AHRR DNAm had a clinically relevant association with prevalent cardiovascular disease (CVD) and compare its predictive performance with self-reported smoking assessments. Methods: Whole blood cg05575921 (AHRR) DNAm was assessed using a simple droplet digital PCR assay in a cohort of 2784 elderly individuals. DNAm values were used to impute smoking status and its independent association with prevalent CVD. Results: Consistent with previous reports, cg05575921 (AHRR) had significant, sensitive, and specific associations with self-reported smoking status (SRSS: never, ex-, current. 21 years, ex-smoker quit <21 years, and current smoker), remained significantly associated with CVD after covariant adjustment, which included SRSS (OR 2.5, 3.1, and 6.0, p < .0001, respectively). Even among never smokers, cg05575921 values were also significantly associated with CVD (Mann–Whitney U test p < .0001). Conclusions: Imputed (cg05575921 AHRR) DNAm smoking status appears to have a significant and independent association with the prevalence of CVD. This association is stronger than that of conventional SRSS and may suggest potential utility to improve existing CVD risk prediction scores. Implications: The results of this study were consistent with previous reports showing that the DNA methylation status of cg05575921 is highly accurate in identifying smoking status (current, ex-smokers, or never smokers), including the length of time an ex-smoker had quit. The marker’s levels also had a strong relationship with prevalent CVD, including after adjusting for other risk factors, such as age, diabetes, and even self-reported smoking status. This study makes a strong contribution to a growing body of work suggesting that this DNAm marker may have substantial clinical utility to aid “precision-medicine” chronic disease risk prediction.

Background: Heart valve disease can result in high morbidity and impairment of quality of life (QOL) both before and after intervention. However, there are few descriptions of the QOL of people with heart valve disease across the disease course. Aims: We aimed to describe the QOL of people living with heart valve disease through qualitative interviews. Methods: Semi-structured interviews were conducted in people with heart valve disease, their family members, and clinical experts. A simple thematic analysis was used to summarise their perceptions of QOL. Results: We interviewed 34 people with heart valve disease: seven with aortic stenosis, seven with rheumatic heart disease involving the mitral valve, nine with mitral regurgitation, and 11 with valve replacement/repair (mean age 66, 56% female). Three family members and five clinical experts were also interviewed. A key contributor to QOL was fatigue: most participants experienced fatigue, even mild fatigue impaired QOL directly, and severe fatigue had devastating effects on quality of life. Physical limitations impaired QOL due to the loss of ‘normal’ activity rather than objective physical limitation. Symptoms of heart valve disease impaired QOL directly, but the indirect effects of valve disease inspiring worry that reduced confidence and activity led to greater impairment. Conclusions: Fatigue both before and after valve intervention is a contributor to QOL and requires further assessment. Research is recommended into whether fatigue is a specific enough symptom to warrant valvular intervention in heart valve disease.

Heart size is a key indicator of cardiovascular health, influenced by various factors such as sex and body height. We developed a physiology laboratory for second-year undergraduates to support learning of these relationships, which are crucial for understanding cardiac physiology. First, students observed heart size measurements with ultrasound by a professional. Second, they measured anthropometric and cardiovascular parameters. Finally, they explored the basic associations between heart size and the anthropometric and cardiovascular indicators.

Background A staging system for aortic stenosis (AS) based upon the extent of cardiac damage has been proposed to better stratify risk and evaluate the benefit of aortic valve intervention (AVI), especially in those with moderate AS. We sought to evaluate the prognostic value of this staging system. Methods Data from initial clinically indicated echocardiograms performed between 2010 and 2018 in patients >18 years of age were extracted and linked to national outcome data. The combined primary outcome was mortality or hospitalization with heart failure. Results Amongst 24,699 patients, 513 and 920 had moderate and mild AS, respectively. In moderate AS, Stage 0 cardiac damage was present in 9.4%, Stage 1 in 53.7%, Stage 2 in 31.1%, Stage 3 in 3.2%, and Stage 4 in 2.6%. In mild AS, rates were 11.5%, 57.8%, 25.0%, 2.6%, and 3.0% for each consecutive stage. Increasing stage was associated with increased risk of the primary outcome in both moderate (HR 1.62/stage) and mild AS (HR 1.93/stage). After censoring at the time of AVI, increasing stage was also associated with mortality in moderate (HR 1.97/stage) and mild AS (HR 2.06/stage). Conclusion Stage of cardiac damage predicts prognosis in both moderate and mild AS to a similar extent. Outcomes may therefore not be fully related to the haemodynamic consequences of valve disease, and hence may not be entirely reversible after valve intervention. Revised management algorithms focusing on earlier intervention and novel treatment strategies targeting cardiac damage are needed to improve clinical outcomes in patients with AS.

Mechanical load is a potent regulator of cardiac structure and function. Although high workload during heart failure is associated with disruption of cardiomyocyte t‐tubules and Ca²⁺homeostasis, it remains unclear whether changes in preload and afterload may promote adaptive t‐tubule remodelling. We examined this issue by first investigating isolated effects of stepwise increases in load in cultured rat papillary muscles. Both preload and afterload increases produced a biphasic response, with the highest t‐tubule densities observed at moderate loads, whereas excessively low and high loads resulted in low t‐tubule levels. To determine the baseline position of the heart on this bell‐shaped curve, mice were subjected to mildly elevated preload or afterload (1 week of aortic shunt or banding). Both interventions resulted in compensated cardiac function linked to increased t‐tubule density, consistent with ascension up the rising limb of the curve. Similar t‐tubule proliferation was observed in human patients with moderately increased preload or afterload (mitral valve regurgitation, aortic stenosis). T‐tubule growth was associated with larger Ca²⁺transients, linked to upregulation of L‐type Ca²⁺channels, Na⁺–Ca²⁺exchanger, mechanosensors and regulators of t‐tubule structure. By contrast, marked elevation of cardiac load in rodents and patients advanced the heart down the declining limb of the t‐tubule–load relationship. This bell‐shaped relationship was lost in the absence of electrical stimulation, indicating a key role of systolic stress in controlling t‐tubule plasticity. In conclusion, modest augmentation of workload promotes compensatory increases in t‐tubule density and Ca²⁺cycling, whereas this adaptation is reversed in overloaded hearts during heart failure progression. image Key points: Excised papillary muscle experiments demonstrated a bell‐shaped relationship between cardiomyocyte t‐tubule density and workload (preload or afterload), which was only present when muscles were electrically stimulated. Thein vivoheart at baseline is positioned on the rising phase of this curve because moderate increases in preload (mice with brief aortic shunt surgery, patients with mitral valve regurgitation) resulted in t‐tubule growth. Moderate increases in afterload (mice and patients with mild aortic banding/stenosis) similarly increased t‐tubule density. T‐tubule proliferation was associated with larger Ca²⁺transients, with upregulation of the L‐type Ca²⁺channel, Na⁺–Ca²⁺exchanger, mechanosensors and regulators of t‐tubule structure. By contrast, marked elevation of cardiac load in rodents and patients placed the heart on the declining phase of the t‐tubule–load relationship, promoting heart failure progression. The dependence of t‐tubule structure on preload and afterload thus enables both compensatory and maladaptive remodelling, in rodents and humans.