Evaluating initiation and real-world tolerability of dapagliflozin for the management of HFrEF.

Untreated heart failure with reduced ejection fraction (HFrEF) has a one-year mortality rate of 40%. The DAPA-HF trial found that dapagliflozin reduces mortality and heart failure (HF) hospitalisation by 17% and 30%, respectively. We describe the initiation and real-world tolerability of dapagliflozin for the management of HFrEF at a large university teaching hospital in central London. We reviewed 118 HFrEF patients initiated on dapagliflozin from January to August 2021 in both inpatient and outpatient settings using the Trust's electronic records. A total of 69 (58.4%) patients were on optimised HF pharmacological therapy upon initiation of dapagliflozin. Dapagliflozin was discontinued in 12 (13.0%) patients. Twenty-three (42.6%) patients either discontinued or had a dose reduction in loop diuretics post-initiation of dapagliflozin. In clinical practice, early initiation of dapagliflozin is safe, well-tolerated and resulted in earlier discontinuation or dose reduction in loop diuretics, providing opportunities to further optimise other HF medicines. This retrospective observational study supports the safety of the updated European Society of Cardiology (ESC) guidelines to initiate all four key HF medicines to minimise delays in HF treatment optimisation, which could translate to reduced National Health Service healthcare costs through fewer HF hospitalisations.

Age matters: differences in exercise-induced cardiovascular remodelling in young and middle aged healthy sedentary individuals.

AIMS: Remodelling of the cardiovascular system (including heart and vasculature) is a dynamic process influenced by multiple physiological and pathological factors. We sought to understand whether remodelling in response to a stimulus, exercise training, altered with healthy ageing. METHODS: A total of 237 untrained healthy male and female subjects volunteering for their first time marathon were recruited. At baseline and after 6 months of unsupervised training, race completers underwent tests including 1.5T cardiac magnetic resonance, brachial and non-invasive central blood pressure assessment. For analysis, runners were divided by age into under or over 35 years (U35, O35). RESULTS: Injury and completion rates were similar among the groups; 138 runners (U35: n = 71, women 49%; O35: n = 67, women 51%) completed the race. On average, U35 were faster by 37 minutes (12%). Training induced a small increase in left ventricular mass in both groups (3 g/m2, P < 0.001), but U35 also increased ventricular cavity sizes (left ventricular end-diastolic volume (EDV)i +3%; left ventricular end-systolic volume (ESV)i +8%; right ventricular end-diastolic volume (EDV)i +4%; right ventricular end-systolic volume (ESV)i +5%; P < 0.01 for all). Systemic aortic compliance fell in the whole sample by 7% (P = 0.020) and, especially in O35, also systemic vascular resistance (-4% in the whole sample, P = 0.04) and blood pressure (systolic/diastolic, whole sample: brachial -4/-3 mmHg, central -4/-2 mmHg, all P < 0.001; O35: brachial -6/-3 mmHg, central -6/-4 mmHg, all P < 0.001). CONCLUSION: Medium-term, unsupervised physical training in healthy sedentary individuals induces measurable remodelling of both heart and vasculature. This amount is age dependent, with predominant cardiac remodelling when younger and predominantly vascular remodelling when older.

Lack of morphometric evidence for ventricular compaction in humans.

The remodeling of the compact wall by incorporation of trabecular myocardium, referred to as compaction, receives much attention because it is thought that its failure causes left ventricular non-compaction cardiomyopathy (LVNC). Although the notion of compaction is broadly accepted, the nature and strength of the evidence supporting this process is underexposed. Here, we review the literature that quantitatively investigated the development of the ventricular wall to understand the extent of compaction in humans, mice, and chickens. We queried PubMed using several search terms, screened 1127 records, and selected 56 publications containing quantitative data on ventricular growth. For humans, only 34 studies quantified wall development. The key premise of compaction, namely a reduction of the trabecular layer, was never documented. Instead, the trabecular layer grows slower than the compact wall in later development and this changes wall architecture. There were no reports of a sudden enlargement of the compact layer (from incorporated trabeculae), be it in thickness, area, or volume. Therefore, no evidence for compaction was found. Only in chickens, a sudden increase in compact myocardial thickness layer was reported coinciding with a decrease in trabecular thickness. In mice, morphometric and lineage tracing investigations have yielded conflicting results that allow for limited compaction to occur. In conclusion, compaction in human development is not supported while rapid intrinsic growth of the compact wall is supported in all species. If compaction takes place, it likely plays a much smaller role in determining wall architecture than intrinsic growth of the compact wall.

Energy drink-induced cardiomyopathy.

We report a case of severe biventricular heart failure potentially related to excessive energy drink consumption in a 21-year-old man. The patient presented with a 4-month history of shortness of breath on exertion, orthopnoea and weight loss. Transthoracic echocardiography demonstrated severely impaired biventricular systolic function and bilateral ventricular thrombi, subsequently confirmed on cardiac magnetic resonance imaging, which found in addition no oedema, inflammation or focal fibrosis. Blood tests, renal ultrasound and subsequent abdominal MRI demonstrated severe renal failure caused by a chronic obstructive uropathy, long-standing and previously undiagnosed. There was no significant past medical, family or social history other than excessive intake of an energy drink. This case report adds to the growing concern in the literature about the potential cardiotoxic effects of energy drinks, which should be considered when assessing young patients presenting with a non-ischaemic dilated cardiomyopathy.

Diagnostic yield and financial implications of a nationwide electrocardiographic screening programme to detect cardiac disease in the young.

AIMS: There is limited information on the role of screening with electrocardiography (ECG) for identifying cardiovascular diseases associated with sudden cardiac death (SCD) in a non-select group of adolescents and young adults in the general population. METHODS AND RESULTS: Between 2012 and 2014, 26 900 young individuals (aged 14-35 years) were prospectively evaluated with a health questionnaire and ECG. Individuals with abnormal results underwent secondary investigations, the costs of which were being based on the UK National Health Service tariffs. Six hundred and seventy-five (2.5%) individuals required further investigation for an abnormal health questionnaire, 2175 (8.1%) for an abnormal ECG, and 114 (0.5%) for both. Diseases associated with young SCD were identified in 88 (0.3%) individuals of which 15 (17%) were detected with the health questionnaire, 72 (81%) with ECG and 2 (2%) with both. Forty-nine (56%) of these individuals received medical intervention beyond lifestyle modification advice in the follow-up period of 24 months. The overall cost of the evaluation process was €97 per person screened, €17 834 per cardiovascular disease detected, and €29 588 per cardiovascular disease associated with SCD detected. Inclusion of ECG was associated with a 36% cost reduction per diagnosis of diseases associated with SCD compared with the health questionnaire alone. CONCLUSION: The inclusion of an ECG to a health questionnaire is associated with a five-fold increase in the ability to detect disease associated with SCD in young individuals and is more cost effective for detecting serious disease compared with screening with a health questionnaire alone.

Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation.

BACKGROUND: Marathon running in novices represents a natural experiment of short-term cardiovascular remodeling in response to running training. We examine whether this stimulus can produce exercise-induced left ventricular (LV) trabeculation. METHODS: Sixty-eight novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study. RESULTS: After 17 weeks unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory inter-observer agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no subject demonstrating clear evidence of a cardiomyopathy. CONCLUSION: Training for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis.

Differentiation between athlete's heart and dilated cardiomyopathy in athletic individuals.

OBJECTIVE: Distinguishing early dilated cardiomyopathy (DCM) from physiological left ventricular (LV) dilatation with LV ejection fraction <55% in athletes (grey zone) is challenging. We evaluated the role of a cascade of investigations to differentiate these two entities. METHODS: Thirty-five asymptomatic active males with DCM, 25 male athletes in the 'grey zone' and 24 male athletes with normal LV ejection fraction underwent N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement, ECG and exercise echocardiography. Grey-zone athletes and patients with DCM underwent cardiovascular magnetic resonance (CMR) and Holter monitoring. RESULTS: Larger LV cavity dimensions and lower LV ejection fraction were the only differences between grey-zone and control athletes. None of the grey-zone athletes had abnormal NT-proBNP, increased ectopic burden/complex arrhythmias or pathological late gadolinium enhancement on CMR. These features were also absent in 71%, 71% and 50% of patients with DCM, respectively. 95% of grey-zone athletes and 60% of patients with DCM had normal ECG. During exercise echocardiography, 96% grey-zone athletes increased LV ejection fraction by >11% from baseline to peak exercise compared with 23% of patients with DCM (p<0.0001). Peak LV ejection fraction was >63% in 92% grey-zone athletes compared with 17% patients with DCM (p<0.0001). Failure to increase LV ejection fraction >11% from baseline to peak exercise or achieve a peak LV ejection fraction >63% had sensitivity of 77% and 83%, respectively, and specificity of 96% and 92%, respectively, for predicting DCM. CONCLUSION: Comprehensive assessment using a cascade of routine investigations revealed that exercise stress echocardiography has the greatest discriminatory value in differentiating between grey-zone athletes and asymptomatic patients with DCM. Our findings require validation in larger studies.

Cardiovascular Remodeling Experienced by Real-World, Unsupervised, Young Novice Marathon Runners.

AIMS: Marathon running is a popular ambition in modern societies inclusive of non-athletes. Previous studies have highlighted concerning transient myocardial dysfunction and biomarker release immediately after the race. Whether this method of increasing physical activity is beneficial or harmful remains a matter of debate. We examine in detail the real-world cardiovascular remodeling response following competition in a first marathon. METHODS: Sixty-eight novice marathon runners (36 men and 32 women) aged 30 ± 3 years were investigated 6 months before and 2 weeks after the 2016 London Marathon race in a prospective observational study. Evaluation included electrocardiography, cardiopulmonary exercise testing, echocardiography, and cardiovascular magnetic resonance imaging. RESULTS: After 17 weeks unsupervised marathon training, runners revealed a symmetrical, eccentric remodeling response with 3-5% increases in left and right ventricular cavity sizes, respectively. Blood pressure (BP) fell by 4/2 mmHg (P < 0.01) with reduction in arterial stiffness, despite only 11% demonstrating a clinically meaningful improvement in peak oxygen consumption with an overall non-significant 0.4 ml/min/kg increase in peak oxygen consumption (P = 0.14). CONCLUSION: In the absence of supervised training, exercise-induced cardiovascular remodeling in real-world novice marathon runners is more modest than previously described and occurs even without improvement in cardiorespiratory fitness. The responses are similar in men and women, who experience a beneficial BP reduction and no evidence of myocardial fibrosis or persistent edema, when achieving average finishing times.

Prevalence of abnormal findings in 230 knees of asymptomatic adults using 3.0 T MRI.

OBJECTIVE: To identify abnormalities in asymptomatic sedentary individuals using 3.0 Tesla high-resolution MRI. MATERIALS AND METHODS: The cohort comprised of 230 knees of 115 uninjured sedentary adults (51 males, 64 females; median age: 44 years). All participants had bilateral knee 3.0 T MRIs. Two senior musculoskeletal radiologists graded all intraarticular knee structures using validated scoring systems. Participants completed Knee Injury and Osteoarthritis Outcome Score questionnaires at the time of the MRI scan. RESULTS: MRI showed abnormalities in the majority (97%) of knees. Thirty percent knees had meniscal tears: horizontal (23%), complex (3%), vertical (2%), radial (2%) and bucket handle (1%). Cartilage and bone marrow abnormalities were prevalent at the patellofemoral joint (57% knees and 48% knees, respectively). Moderate and severe cartilage lesions were common, in 19% and 31% knees, respectively, while moderate and severe bone marrow oedema in 19% and 31% knees, respectively. Moderate-intensity lesion in tendons was found in 21% knees and high-grade tendonitis in 6% knees-the patellar (11% and 2%, respectively) and quadriceps (7% and 2%, respectively) tendons being most affected. Three percent partial ligamentous ruptures were found, especially of the anterior cruciate ligament (2%). CONCLUSION: Nearly all knees of asymptomatic adults showed abnormalities in at least one knee structure on MRI. Meniscal tears, cartilage and bone marrow lesions of the patellofemoral joint were the most common pathological findings. Bucket handle and complex meniscal tears were reported for the first time in asymptomatic knees.

Is the immediate effect of marathon running on novice runners' knee joints sustained within 6 months after the run? A follow-up 3.0 T MRI study.

OBJECTIVE: To evaluate changes in the knee joints of asymptomatic first-time marathon runners, using 3.0 T MRI, 6 months after finishing marathon training and run. MATERIALS AND METHODS: Six months after their participation in a baseline study regarding their knee joints, 44 asymptomatic novice marathoners (17 males, 27 females, mean age 46 years old) agreed to participate in a repeat MRI investigation: 37 completed both a standardized 4-month-long training programme and the marathon (marathon runners); and 7 dropped out during training (pre-race dropouts). The participants already underwent bilateral 3.0 T MRIs: 6 months before and 2 weeks after their first marathon, the London Marathon 2017. This study was a follow-up assessment of their knee joints. Each knee structure was assessed using validated scoring/grading systems at all time points. RESULTS: Two weeks after the marathon, 3 pre-marathon bone marrow lesions and 2 cartilage lesions showed decrease in radiological score on MRI, and the improvement was sustained at the 6-month follow-up. New improvements were observed on MRI at follow-up: 5 pre-existing bone marrow lesions and 3 cartilage lesions that remained unchanged immediately after the marathon reduced in their extent 6 months later. No further lesions appeared at follow-up, and the 2-week post-marathon lesions showed signs of reversibility: 10 of 18 bone marrow oedema-like signals and 3 of 21 cartilage lesions decreased on MRI. CONCLUSION: The knees of novice runners achieved sustained improvement, for at least 6 months post-marathon, in the condition of their bone marrow and articular cartilage.