The development of inherited cardiac conditions services: current position and future perspectives.

BACKGROUND: Over the last two decades, inherited cardiac conditions (ICC) centres have emerged with the aim of improving outcomes for patients and their families, through early diagnosis, genetic testing, risk assessment and specialist treatment. SOURCES OF DATA: A literature search was performed using PubMed (https://pubmed.ncbi.nlm.nih.gov/). Commissioned ICC service reviews from NHS England, NHS Improvement and PHG Foundation were evaluated. AREAS OF AGREEMENT: ICC patient management requires a multi-disciplinary approach. ICC services are predominantly based within tertiary centres. Despite expansion, provision of care remains inadequate to meet rising demands. Access to services is inconsistent, partly due to geographic variation and lack of standardized pathways. AREAS OF CONTROVERSY: The optimal ICC care model remains undecided, although there is growing interest in 'hub-and-spoke' networks, which could aid secondary and tertiary service integration and repatriation of care. GROWING POINTS: Genetic mainstreaming is a priority for the Genomic Medicine Service Alliance. The benefits of telehealth and virtual clinics have been validated by their use during the COVID-19 pandemic. Other innovations to improve resource efficiency, such as clinical scientist-led and nurse-led clinics, show promise. AREAS TIMELY FOR DEVELOPING RESEARCH: An update for the NHS ICC service specifications is planned that appears well timed given the rapid evolution of the ICC landscape in the decade since last review. This has the potential to address needs including national audit, standardized pathways and ICC networks to improve governance and equity of care. Delegation of commissioning for specialist services to integrated care systems may also provide opportunity for increased regional direction.

Multi-catheter cryotherapy compared with radiofrequency ablation in long-standing persistent atrial fibrillation: a randomized clinical trial.

AIMS: Restoring sinus rhythm (SR) by ablation alone is an endpoint used in radiofrequency (RF) ablation for long-standing persistent atrial fibrillation (AF) but not with cryotherapy. The simultaneous use of two cryotherapy catheters can improve ablation efficiency; we compared this with RF ablation in chronic persistent AF aiming for termination to SR by ablation alone. METHODS AND RESULTS: Consecutive patients undergoing their first ablation for persistent AF of >6 months duration were screened. A total of 100 participants were randomized 1:1 to multi-catheter cryotherapy or RF. For cryotherapy, a 28-mm Arctic Front Advance was used in tandem with focal cryoablation catheters. Open-irrigated, non-force sensing catheters were used in the RF group with a 3D mapping system. Pulmonary vein (PV) isolation and non-PV triggers were targeted. Participants were followed up at 6 and 12 months, then yearly. Acute PVI was achieved in all cases. More patients in the multi-catheter cryotherapy group were restored to SR by ablation alone, with a shorter procedure duration. Sinus rhythm continued to the last available follow-up in 16/49 patients (33%) in the multi-catheter at 3.0 ± 1.6 years post-ablation and in 12/50 patients (24%) in the RF group at 4.0 ± 1.2 years post-ablation. The yearly rate of arrhythmia recurrence was similar. CONCLUSION: Multi-catheter cryotherapy can restore SR by ablation alone in more cases and more quickly than RF ablation. Long-term success is difficult to achieve by either methods and is similar with both.

Electrocardiographic differentiation between 'benign T-wave inversion' and arrhythmogenic right ventricular cardiomyopathy.

AIMS: To characterize the most common electrocardiographic (ECG) abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), including anterior T-wave inversion (TWI) and to compare the characteristics of TWI in patients with ARVC and in a cohort of young healthy athletes and sedentary individuals. METHODS AND RESULTS: The study population consisted of 162 patients with a definite diagnosis of ARVC and 129 young controls with anterior TWI. Cardiac disease was excluded in all controls after a comprehensive diagnostic work-up. The ECG was abnormal in 131 patients with ARVC (81%). Abnormalities included anterior TWI (n = 82, 51%), QRS duration ratio V2:V5 >1.2 (n = 51, 31%), prolonged terminal S wave activation duration in V2 >55 ms (n = 42, 26%), inferior TWI (n = 30, 18%), and lateral TWI (n = 26, 16%). The J-point preceding anterior TWI was <0.1 mV in 80/82 (98%) patients with ARVC and in 98 (76%) controls. Among the ARVC patients with anterior TWI, 62 (77%) showed at least one additional abnormal feature, most commonly QRS duration ratio V2:V5 > 1.2 (52%) and inferior or lateral TWI (47%). CONCLUSION: The ECG is frequently abnormal in patients with ARVC and anterior TWI is the most common feature. Anterior TWI is usually accompanied by other abnormalities in ARVC, which are uncommon in healthy individuals. J point <0.1 mV preceding anterior TWI is not specific to ARVC and is observed in the majority of healthy individuals, including athletes, indicating a limited role for differentiating physiology or normal variants from ARVC.

Novel electrocardiographic criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

AIMS: In order to improve the electrocardiographic (ECG) diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC), we evaluated novel quantitative parameters of the QRS complex and the value of bipolar chest leads (CF leads) computed from the standard 12 leads. METHODS AND RESULTS: We analysed digital 12-lead ECGs in 44 patients with ARVC, 276 healthy subjects including 44 age and sex-matched with the patients and 36 genotyped members of ARVC families. The length and area of the terminal S wave in V1 to V3 were measured automatically using a common for all 12 leads QRS end. T wave negativity was assessed in V1 to V6 and in the bipolar CF leads computed from the standard 12 leads. The length and area of the terminal S wave were significantly shorter, whereas the S wave duration was significantly longer in ARVC patients compared with matched controls. Among members of ARVC families, those with mutations (n = 15) had shorter QRS length in V2 and V3 and smaller QRS area in lead V2 compared with those without mutations (n = 20). In ARVC patients, the CF leads were diagnostically superior to the standard unipolar precordial leads. Terminal S wave duration in V1 >48 ms or major T wave negativity in CF leads separated ARVC patients from matched controls with 90% sensitivity and 86% specificity. CONCLUSION: The terminal S wave length and area in the right precordial leads are diagnostically useful and suitable for automatic analysis in ARVC. The CF leads are diagnostically superior to the unipolar precordial leads.

Echocardiographic Assessment of Mantle Radiation Mitral Stenosis.

The long-term sequelae of mantle radiotherapy include lung disease and cardiac disorders. Dyspnea on exertion is a common complaint and can be due to one or more pathologies. We describe a case of mantle radiotherapy-induced mitral stenosis, characterized by aorto-mitral continuity calcification and absent commissural fusion which precludes balloon valvotomy. The latency period is long, and this patient presented 42 years after radiotherapy. Importantly, as previously described with radiation-induced valve disease, significant mitral stenosis developed 10 years after surgery for significant aortic stenosis. Two-dimensional and three-dimensional transthoracic and transesophageal echocardiography should be considered during assessment of symptomatic survivors of Hodgkin's disease where the index of suspicion for valvular stenosis increases over time. Given the natural history of mantle radiation valvular disease, a lower threshold for surgical intervention in radiation-induced mitral stenosis may need to be considered if cardiac surgery is planned for other reasons in order to avoid repeated sternotomy in patients with prior irradiation.

Clinical usefulness, angiographic characteristics, and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive white patients with unobstructed coronary arteries.

BACKGROUND: Coronary spasm can cause myocardial ischemia and angina in patients with and those without obstructive coronary artery disease. However, provocation tests using intracoronary acetylcholine administration are rarely performed in clinical routine in the United States and Europe. Thus, we assessed the clinical usefulness, angiographic characteristics, and safety of intracoronary acetylcholine provocation testing in white patients with unobstructed coronary arteries. METHODS AND RESULTS: From September 2007 to June 2010, a total of 921 consecutive patients (362 men, mean age 62±12years) who underwent diagnostic angiography for suspected myocardial ischemia and were found to have unobstructed coronary arteries (no stenosis ≥50%) were enrolled. The intracoronary acetylcholine provocation testing was performed directly after angiography according to a standardized protocol. Three hundred forty-six patients (35%) reported chest pain at rest, 222 (22%) reported chest pain on exertion, 238 (24%) reported a combination of effort and resting chest pain, and 41 (4%) presented with troponin-positive acute coronary syndrome. The overall frequency of epicardial spasm (>75% diameter reduction with angina and ischemic ECG shifts) was 33.4%, and the overall frequency of microvascular spasm (angina and ischemic ECG shifts without epicardial spasm) was 24.2%. Epicardial spasm was most often diffuse and located in the distal coronary segments (P<0.01). No fatal or irreversible nonfatal complications occurred. However, 9 patients (1%) had minor complications (nonsustained ventricular tachycardia [n=1], fast paroxysmal atrial fibrillation [n=1], symptomatic bradycardia [n=6], and catheter-induced spasm [n=1]). CONCLUSIONS: Epicardial and microvascular spasm are frequently found in white patients with unobstructed coronary arteries. Epicardial spasm is most often diffuse and located in the distal coronary segments. The intracoronary acetylcholine provocation test is a safe technique to assess coronary vasomotor function.

Feasibility and efficacy of simultaneous pulmonary vein isolation and cavotricuspid isthmus ablation using cryotherapy.

INTRODUCTION: Pulmonary vein isolation (PVI) and cavotricuspid isthmus (CTI) ablation are often performed as part of the same procedure. In many cases, PVI is performed by cryotherapy and then CTI ablation by radiofrequency (RF) energy. We sought to determine whether it is more efficient to perform CTI ablation simultaneously with PVI using separate cryogenerators. METHODS AND RESULTS: We performed cryoablation of the CTI during PVI with the Arctic Front cryoballoon in 25 consecutive patients with clinical indications for both (PVI/CTI-cryo group). Procedural data were compared to those of 25 matched patients who underwent PVI only by the same operator (PVI-only group), and 25 patients who underwent PVI by cryotherapy and CTI ablation using RF energy sequentially during the same procedure (PVI/CTI-mixed group). No complication occurred. All veins were isolated; bidirectional CTI block was demonstrated in all cases where it was attempted, except for 1 patient in the PVI/CTI-mixed group. Procedure and fluoroscopy duration were significantly shorter in the PVI/CTI-cryo group (162 ± 34 and 24 ± 5 minutes) than in the PVI/CTI-mixed group (209 ± 46 minutes, P < 0.001 and 59 ± 28 minutes, P < 0.001). Procedure and fluoroscopy duration in the PVI-only group (155 ± 32 and 22 ± 8 minutes) were similar to those in the PVI/CTI-cryo group (P = NS) but significantly shorter than in the PVI/CTI-mixed group (P < 0.001 for both). Clinical outcomes were similar in all groups. CONCLUSION: When CTI ablation is performed with RF energy after PVI by cryoballoon, it adds significantly to the procedure and fluoroscopy durations; when performed contemporaneously using cryotherapy at both sites, the procedure and fluoroscopy durations are not prolonged.

Clinical significance of electrocardiographic right ventricular hypertrophy in athletes: comparison with arrhythmogenic right ventricular cardiomyopathy and pulmonary hypertension.

AIMS: Pre-participation cardiovascular screening of young athletes may prevent sports-related sudden cardiac deaths. Recognition of physiological electrocardiography (ECG) changes in healthy athletes has improved the specificity of screening while maintaining sensitivity for disease. The study objective was to determine the clinical significance of electrocardiographic right ventricular hypertrophy (RVH) in athletes. METHODS AND RESULTS: Between 2010 and 2012, 868 subjects aged 14-35 years (68.8% male) were assessed using ECG and echocardiography (athletes; n = 627, sedentary controls; n = 241). Results were compared against patients with established right ventricular (RV) pathology (arrhythmogenic right ventricular cardiomyopathy, n = 68; pulmonary hypertension, n = 30). Sokolow-Lyon RVH (R[V1]+S[V5orV6] > 1.05 mV) was more prevalent in athletes than controls (11.8 vs. 6.2%, P = 0.017), although RV wall thickness (RVWT) was similar (4.0 ± 1.0 vs. 3.9 ± 0.9 mm, P = 0.18). Athletes exhibiting electrocardiographic RVH were predominantly male (95.9%), and demonstrated similar RV dimensions and function to athletes with normal electrocardiograms (RVWT; 4.0 ± 1.1 vs. 4.0 ± 0.9 mm, P = 0.95, RV basal dimension; 42.7 ± 5.2 vs. 42.1 ± 5.9 mm, P = 0.43, RV fractional area change; 40.6 ± 7.6 vs. 42.2 ± 8.1%, P = 0.14). Sensitivity and specificity of Sokolow-Lyon RVH for echocardiographic RVH (>5 mm) were 14.3 and 88.2%, respectively. Further evaluation including cardiac magnetic resonance imaging did not diagnose right ventricular pathology in any athlete. None of the cardiomyopathic or pulmonary hypertensive patients exhibited voltage RVH without additional ECG abnormalities. CONCLUSION: Electrocardiographic voltage criteria for RVH are frequently fulfilled in healthy athletes without underlying RV pathology, and should not prompt further evaluation if observed in isolation. Recognition of this phenomenon should reduce the burden of investigations after pre-participation ECG screening without compromising sensitivity for disease.

Implementing a clinical scientist-led screening clinic for hypertrophic and dilated cardiomyopathies.

BACKGROUND: The burden of screening for inherited cardiac conditions on health services grows ever larger, with each new diagnosis necessitating screening of additional family members. Screening these usually asymptomatic, low-risk individuals is currently performed by consultant cardiologists, consuming vital clinic resources that could otherwise be diverted to sicker patients requiring specialist consultant input. Clinical scientists now constitute a highly skilled and often underutilised group of individuals with training in areas such as clinical evaluation, 12-lead electrocardiography (ECG) interpretation, and echocardiography. These skills place them in a unique position to offer a full screening evaluation in a single consultation. The aim of this study was to implement and evaluate a novel clinical scientist-led screening clinic for first-degree relatives of patients with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The clinical scientist-led screening clinic was established at a London tertiary centre to allow review of asymptomatic, first-degree relatives of patients with a confirmed diagnosis of HCM or DCM, independent of a cardiology consultant. Patients were evaluated with history, examination, ECG, and echocardiography, with further investigations if deemed necessary. A retrospective review was performed of the first 200 patients seen in the clinic. RESULTS: Of the 200 individuals reviewed between September 2019 and July 2022, 99 had a proband with HCM and 101 a proband with DCM. Overall, 169 individuals (85%) revealed normal screenings and were discharged. Thirty-one individuals (15.5%), all asymptomatic, revealed ECG changes and/or significant echocardiographic findings. Of these, 21 individuals (10.5% of the total cohort) were subsequently diagnosed with a cardiomyopathy or early phenotypic changes consistent with a cardiomyopathy (11 with HCM and 10 with DCM). These individuals were referred on to an inherited cardiac conditions consultant clinic for regular follow-up. Overall, 179 consultant clinic appointments were saved which could instead be allocated to patients requiring specialist consultant input. CONCLUSIONS: This is the first description of a clinical scientist-led screening clinic for first-degree relatives of patients with HCM and DCM. The findings demonstrate that implementation of such a service into routine clinical practice is feasible, effective, safe, and can free up capacity in consultant clinics for patients requiring specialist input.