The right ventricle in Adult Congenital Heart Disease

Heart failure (HF) and sudden cardiac death (SCD) in congenital heart disease (CHD) is prevalent and can relate to abnormal right ventricular (RV) physiology and abnormalities of QRS duration, and QRS, JT and QT dispersion (d). Characterising disease and identifying factors that may predict adverse outcome in those with either a subpulmonary or subsystemic RV, as well as investigating potential avenues to ameliorate abnormal RV physiology is necessary to improve outcomes in this young population. I undertook several studies during the course of this Thesis to examine and further understand these two separate physiological substrates: In the first I studied the effect of isolated percutaneous (PPVI) pulmonary valve implantation on surface ECG parameters. PPVI represents a pure model of RV mechanical and electrophysiological changes post replacement as compared to surgical replacement: Ninety nine PPVI procedures in patients with CHD (aged 23.1±10 yrs) were studied pre, post and 1-year following PPVI with serial ECG’s and echocardiography/ magnetic resonance imaging (CMR). 43% had pulmonary stenosis, 27% pulmonary regurgitation (PR) and 29% mixed lesions. In those with predominantly PR (n=26), QRS duration decreased significantly (135±27 to 128±29ms; p=0.007). However, in the total cohort no significant change in QRS duration at 1 year was observed (137±29 to 134±29ms). QTc, QRSd, QTd and JTd all significantly reduced at 1 yr (p≤0.001). RV EDV correlated with pre-procedure QRS duration (r=0.34; p104ms and QTc >406ms had a sensitivity/specificity for predicting death of 96%/66% and 96%/56% respectively. Two year mortality was 36% when QRS104ms (p<0.0001 for difference). Further, compared to those with uncomplicated surgery, patients with complex surgical history had higher NT-proBNP levels (55±26 vs 20±35pmol/L; P=0.002) and longer QRS duration (116±28ms vs 89±11ms; P=0.0004) whilst showing no difference in NYHA class and RV function. There was a significant relationship between diastolic and systolic RV volumes and both NT-proBNP levels (r=0.43, P=0.01; r=0.53, P=0.001 respectively) and QRS duration (r=0.47, P=0.004; r=0.53, P=0.001 respectively). These findings suggest that QRS width and corrected QTc interval on surface ECG are associated with increased risk of death in adults late after atrial switch repair of TGA. Given that a QRS of only 104ms defines a high risk population, careful examination of the ECG is desirable in all patients and therapy to reduce risk attempted. Further, together with these simple surface ECG parameters, circulating NT-proBNP levels constitute safe, cost effective and widely available surrogate markers of systemic RV function and provide additional information on heart failure status. Both measures hold promise as prognostic markers and their association with long-term outcome should be determined. Lastly, I examined the mechanisms of late RV failure and studied their relationship to subjective quality of life assessment as this are poorly characterised. Equilibrium Contrast CMR imaging was used to quantify extracellular volume (ECV) in the septum and RV free wall of adults presenting to a specialist clinic late after atrial redirection surgery for TGA. These were compared to age and sex matched healthy volunteers. Patients were also assessed with a standardised CMR protocol, NT-proBNP and surface ECG measurement, and cardiopulmonary exercise (CPEX) testing. Patients also completed a Minnesota Living With Heart Failure Questionnaire (MLHFQ) self assessment. I determined that mean septal ECV was significantly higher in patients than controls (0.254±0.036, vs 0.230±0.032; p=0.03). NT-proBNP positively related to septal ECV (p=0.04; r=0.55) but chronotropic index (CI) during CPEX testing negatively related to ECV (p=0.04; r=-0.58). No relationship was seen with other CMR or CPEX parameters. Median MLHFQ score was 6(2-19), median NT-pro BNP 24 (16-43) and mean peak VO2 24±7mL/kg/min. There was a significant positive correlation between MLHFQ score and NT-proBNP (p=0.001, r=0.34) and a significant negative correlation with peak VO2 (p=0.001, r=0.49. ). Septal interstitial expansion is seen in adults late after atrial redirection surgery for TGA. It correlates well with NT-proBNP and CI and may have a role in the development of RV systolic impairment. The MLHFQ correlates highly with NT-proBNP and exercise capacity in patients with systemic RV impairment. The ability of the MLHFQ in predicting HF events and prognosis in adults with CHD needs further evaluation

Haemodynamic consequences of targeted single- and dual-site right ventricular pacing in adults with congenital heart disease undergoing surgical pulmonary valve replacement

Aims The purpose of this study was to create an epicardial electroanatomic map of the right ventricle (RV) and then apply post-operative-targeted single- and dual-site RV temporary pacing with measurement of haemodynamic parameters. Cardiac resynchronization therapy is an established treatment for symptomatic left ventricular (LV) dysfunction. In congenital heart disease, RV dysfunction is a common cause of morbidity—little is known regarding the potential benefits of CRT in this setting. Methods and results Sixteen adults (age = 32 ± 8 years; 6 M, 10 F) with right bundle branch block (RBBB) and repaired tetralogy of Fallot (n = 8) or corrected congenital pulmonary stenosis (n = 8) undergoing surgical pulmonary valve replacement (PVR) for pulmonary regurgitation underwent epicardial RV mapping and haemodynamic assessment of random pacing configurations including the site of latest RV activation. The pre-operative pulmonary regurgitant fraction was 49 ± 10%; mean LV end-diastolic volume (EDV) 85 ± 19 mL/min/m2 and RVEDV 183 ± 89 mL/min/m2 on cardiac magnetic resonance imaging. The mean pre-operative QRS duration is 136 ± 26 ms. The commonest site of latest activation was the RV free wall and DDD pacing here alone or combined with RV apical pacing resulted in significant increases in cardiac output (CO) vs. AAI pacing (P < 0.01 all measures). DDDRV alternative site pacing significantly improved CO by 16% vs. AAI (P = 0.018), and 8.5% vs. DDDRV apical pacing (P = 0.02). Conclusion Single-site RV pacing targeted to the region of latest activation in patients with RBBB undergoing PVR induces acute improvements in haemodynamics and supports the concept of ‘RV CRT’. Targeted pacing in such patients has therapeutic potential both post-operatively and in the long term

Urinary drug metabolite testing in chronic heart failure patients indicates high levels of adherence with life-prolonging therapies

Aims Despite medical therapy for heart failure (HF) having proven benefits of improving quality of life and survival, many patients remain under-treated. This may be due to a combination of under-prescription by medical professionals and poor adherence from patients. In HF, as with many other chronic diseases, adherence to medication can deteriorate over time particularly when symptoms are well controlled. Therefore, detecting and addressing non-adherence has a crucial role in the management of HF. Significant flaws and inaccuracies exist in the methods currently used to assess adherence such as patient reporting, pill counts, and pharmacy fill records. We aim to use high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS) to detect metabolites of HF medications in the urine samples of chronic HF patients. Methods and results Urine samples were collected from 35 patients in a specialist HF clinic. Patients were included if they had an ejection fraction <45% and were taking at least two disease-modifying HF medications. They were excluded if they had been admitted to hospital for HF in the 3 months preceding clinic attendance. These samples were sent for HPLC-MS and tested for all HF medications prescribed for that patient. A high rate of complete adherence of 89% was detected in these patients, with 94% being partially adherent (at least one HF medication detected) to therapy (at least one HF medication detected). This analysis also highlighted that mineralocorticoid antagonists represent both the most under-prescribed (67%) and poorly adhered (75%) medication class. Conclusions This analysis revealed a surprisingly high level of adherence to disease-modifying therapy in chronic HF patients and highlights that most of our ‘total’ under-treatment is likely to be from a failure to prescribe rather than a failure to adhere. Testing for metabolites of disease-modifying HF drugs in urine using HPLC-MS is feasible and is a useful adjunct to a specialist HF service. At present, the distinction between treatment failure and failure to take treatment is not always clear, which is important because the investigation and potential solutions are different. The former needs initiation of additional therapies and consideration of additional diagnoses, whereas the latter requires strategies to understand reasons underlying poor adherence and collaborative working to improve this: the wrong strategy will be ineffective

Survival and health economic outcomes in heart failure diagnosed at hospital admission versus community settings: a propensity-matched analysis

BACKGROUND AND AIMS: Most patients with heart failure (HF) are diagnosed following a hospital admission. The clinical and health economic impacts of index HF diagnosis made on admission to hospital versus community settings are not known. METHODS: We used the North West London Discover database to examine 34 208 patients receiving an index diagnosis of HF between January 2015 and December 2020. A propensity score-matched (PSM) cohort was identified to adjust for differences in socioeconomic status, cardiovascular risk and pre-diagnosis health resource utilisation cost. Outcomes were stratified by two pathways to index HF diagnosis: a 'hospital pathway' was defined by diagnosis following hospital admission; and a 'community pathway' by diagnosis via a general practitioner or outpatient services. The primary clinical and health economic endpoints were all-cause mortality and cost-consequence differential, respectively. RESULTS: The diagnosis of HF was via hospital pathway in 68% (23 273) of patients. The PSM cohort included 17 174 patients (8582 per group) and was matched across all selected confounders (p>0.05). The ratio of deaths per person-months at 24 months comparing community versus hospital diagnosis was 0.780 (95% CI 0.722 to 0.841, p<0.0001). By 72 months, the ratio of deaths was 0.960 (0.905 to 1.020, p=0.18). Diagnosis via hospital pathway incurred an overall extra longitudinal cost of £2485 per patient. CONCLUSIONS: Index diagnosis of HF through hospital admission continues to dominate and is associated with a significantly greater short-term risk of mortality and substantially increased long-term costs than if first diagnosed in the community. This study highlights the potential for community diagnosis-early, before symptoms necessitate hospitalisation-to improve both clinical and health economic outcomes

Smartphone-based remote monitoring in heart failure with reduced ejection fraction: retrospective cohort study of secondary care use and costs

BACKGROUND: Despite effective therapies, the economic burden of heart failure with reduced ejection fraction (HFrEF) is driven by frequent hospitalizations. Treatment optimization and admission avoidance rely on frequent symptom reviews and monitoring of vital signs. Remote monitoring (RM) aims to prevent admissions by facilitating early intervention, but the impact of noninvasive, smartphone-based RM of vital signs on secondary health care use and costs in the months after a new diagnosis of HFrEF is unknown. OBJECTIVE: The purpose of this study is to conduct a secondary care health use and health-economic evaluation for patients with HFrEF using smartphone-based noninvasive RM and compare it with matched controls receiving usual care without RM. METHODS: We conducted a retrospective study of 2 cohorts of newly diagnosed HFrEF patients, matched 1:1 for demographics, socioeconomic status, comorbidities, and HFrEF severity. They are (1) the RM group, with patients using the RM platform for >3 months and (2) the control group, with patients referred before RM was available who received usual heart failure care without RM. Emergency department (ED) attendance, hospital admissions, outpatient use, and the associated costs of this secondary care activity were extracted from the Discover data set for a 3-month period after diagnosis. Platform costs were added for the RM group. Secondary health care use and costs were analyzed using Kaplan-Meier event analysis and Cox proportional hazards modeling. RESULTS: A total of 146 patients (mean age 63 years; 42/146, 29% female) were included (73 in each group). The groups were well-matched for all baseline characteristics except hypertension (P=.03). RM was associated with a lower hazard of ED attendance (hazard ratio [HR] 0.43; P=.02) and unplanned admissions (HR 0.26; P=.02). There were no differences in elective admissions (HR 1.03, P=.96) or outpatient use (HR 1.40; P=.18) between the 2 groups. These differences were sustained by a univariate model controlling for hypertension. Over a 3-month period, secondary health care costs were approximately 4-fold lower in the RM group than the control group, despite the additional cost of RM itself (mean cost per patient GBP £465, US $581 vs GBP £1850, US$2313, respectively; P=.04). CONCLUSIONS: This retrospective cohort study shows that smartphone-based RM of vital signs is feasible for HFrEF. This type of RM was associated with an approximately 2-fold reduction in ED attendance and a 4-fold reduction in emergency admissions over just 3 months after a new diagnosis with HFrEF. Costs were significantly lower in the RM group without increasing outpatient demand. This type of RM could be adjunctive to standard care to reduce admissions, enabling other resources to help patients unable to use RM

Smartphone-based remote monitoring in chronic heart failure: patient & clinician user experience, impact on patient engagement and quality of life

Background Heart failure with reduced ejection fraction (HFrEF) lowers patients' quality of life (QoL) [1]. Digital interventions such as ESC's “Heart Failure Matters” website aim to encourage patient-engagement & self-management [2], which remain major challenges in HFrEF care. Although remote monitoring (RM) has been tested in HFrEF with inconclusive impact on prognosis [3], its impact on patients' experience and engagement is unclear [4]. Furthermore, the perspective of clinicians using RM technologies remains unknown. We present users' experience of Luscii, a novel smartphone-based RM platform enabling HFrEF patients to submit clinical measurements, symptoms, complete educational modules, & communicate with HF specialist nurses (HFSNs). Purpose (I) To evaluate the usage-type & user experience of patients and HFSNs. (II) To assess the impact of using the RM platform on self-reported QoL Methods A two-part retrospective analysis of HFrEF patients from our regional service using the RM platform: Part A: Thematic analysis of patient feedback provided via the platform and a focus group of six HFSNs. Part B: Scores for a locally-devised HF questionnaire (HFQ), depression (PHQ-9) & anxiety (GAD-7) questionnaires were extracted from the RM platform at two timepoints: at on-boarding and 3 months after. Paired non-parametric tests were used to evaluate difference between median scores across the two time points. Results 83 patients (mean age 62 years; 27% female) used the RM platform between April and November 2021. 2 dropped out & 2 died before 3 months. Part A: Patients and HFSNs exchanged information on many topics via the platform, including patient educational modules (Figure 1). Thematic analysis revealed positive and negative impacts with many overlapping subthemes between the two user groups (Figure 2). Part B: At 3 months there was no difference in HFQ score (19 vs. 18, p=0.57, maximum possible score = 50). PHQ-9 (3 vs. 3, p=0.48, maximum possible score = 27) and GAD-7 (5 vs. 3, p=0.54. maximum possible score = 21) scores were low at onboarding and follow-up. Conclusions This evaluation shows smartphone-based RM is feasible in HFrEF with good retention (2% drop-out rate over 3 months, albeit in a cohort with low baseline depression and anxiety levels). The platform serves as an integrated solution for symptom reporting, patient-clinician communication & education. Positive impacts include patient engagement, convenience, admission avoidance & medication optimisation, but there was no corresponding change in QoL scores in the short-term. We find potential pitfalls: information overload for patients & increased workload for clinicians. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Sameer Zaman is supported by UK Research and Innovation [UKRI Centre for Doctoral Training in AI for Healthcare grant number EP/S023283/1]

Self-care of heart failure patients: practical management recommendations from the Heart Failure Association of the European Society of Cardiology.

Self-care is essential in the long-term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self-care is related to medical and person-centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self-care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion

Correction to: Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI).

CORRECTION TO: J CARDIOVASC MAGN RESON (2017) 19: 75. DOI: 10.1186/S12968-017-0389-8: In the original publication of this article [1] the "Competing interests" section was incorrect. The original publication stated the following competing interests

Artificial intelligence, data sensors and interconnectivity: future Opportunities for heart failure

A higher proportion of patients with heart failure have benefitted from a wide and expanding variety of sensor-enabled implantable devices than any other patient group. These patients can now also take advantage of the ever-increasing availability and affordability of consumer electronics. Wearable, on- and near-body sensor technologies, much like implantable devices, generate massive amounts of data. The connectivity of all these devices has created opportunities for pooling data from multiple sensors - so-called interconnectivity - and for artificial intelligence to provide new diagnostic, triage, risk-stratification and disease management insights for the delivery of better, more personalised and cost-effective healthcare. Artificial intelligence is also bringing important and previously inaccessible insights from our conventional cardiac investigations. The aim of this article is to review the convergence of artificial intelligence, sensor technologies and interconnectivity and the way in which this combination is set to change the care of patients with heart failure