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.

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.

Arrhythmogenic cardiomyopathy and differential diagnosis with physiological right ventricular remodelling in athletes using cardiovascular magnetic resonance.

To describe the overlap between structural abnormalities typical of arrhythmogenic right ventricular cardiomyopathy (ARVC) and physiological right ventricular adaptation to exercise and differentiate between pathologic and physiologic findings using CMR. We compared CMR studies of 43 patients (mean age 49 ± 17 years, 49% males, 32 genotyped) with a definitive diagnosis of ARVC with 97 (mean age 45 ± 16 years, 61% males) healthy athletes. CMR was abnormal in 37 (86%) patients with ARVC, but only 23 (53%) fulfilled a major or minor CMR criterion according to the TFC. 7/20 patients who did not fulfil any CMR TFC showed pathological finding (RV RWMA and fibrosis in the LV or LV RWMA). RV was affected in isolation in 17 (39%) patients and 18 (42%) patients showed biventricular involvement. Common RV abnormalities included RWMA (n = 34; 79%), RV dilatation (n = 18; 42%), RV systolic dysfunction (≤ 45%) (n = 17; 40%) and RV LGE (n = 13; 30%). The predominant LV abnormality was LGE (n = 20; 47%). 22/32 (69%) patients exhibited a pathogenic variant: PKP2 (n = 17, 53%), DSP (n = 4, 13%) and DSC2 (n = 1, 3%). Sixteen (16%) athletes exceeded TFC cut-off values for RV volumes. None of the athletes exceeded a RV/LV end-diastolic volume ratio > 1.2, nor fulfilled TFC for impaired RV ejection fraction. The majority (86%) of ARVC patients demonstrate CMR abnormalities suggestive of cardiomyopathy but only 53% fulfil at least one of the CMR TFC. LV involvement is found in 50% cases. In athletes, an RV/LV end-diastolic volume ratio > 1.2 and impaired RV function (RVEF ≤ 45%) are strong predictors of pathology.

Rare Variation in Drug Metabolism and Long QT Genes and the Genetic Susceptibility to Acquired Long QT Syndrome.

BACKGROUND: Acquired long QT syndrome (aLQTS) is a serious unpredictable adverse drug reaction. Pharmacogenomic markers may predict risk. METHODS: Among 153 aLQTS patients (mean age 58 years [range, 14-88], 98.7% White, 85.6% symptomatic), computational methods identified proteins interacting most significantly with 216 QT-prolonging drugs. All cases underwent sequencing of 31 candidate genes arising from this analysis or associating with congenital LQTS. Variants were filtered using a minor allele frequency <1% and classified for susceptibility for aLQTS. Gene-burden analyses were then performed comparing the primary cohort to control exomes (n=452) and an independent replication aLQTS exome sequencing cohort. RESULTS: In 25.5% of cases, at least one rare variant was identified: 22.2% of cases carried a rare variant in a gene associated with congenital LQTS, and in 4% of cases that variant was known to be pathogenic or likely pathogenic for congenital LQTS; 7.8% cases carried a cytochrome-P450 (CYP) gene variant. Of 12 identified CYP variants, 11 (92%) were in an enzyme known to metabolize at least one culprit drug to which the subject had been exposed. Drug-drug interactions that affected culprit drug metabolism were found in 19% of cases. More than one congenital LQTS variant, CYP gene variant, or drug interaction was present in 7.8% of cases. Gene-burden analyses of the primary cohort compared to control exomes (n=452), and an independent replication aLQTS exome sequencing cohort (n=67) and drug-tolerant controls (n=148) demonstrated an increased burden of rare (minor allele frequency<0.01) variants in CYP genes but not LQTS genes. CONCLUSIONS: Rare susceptibility variants in CYP genes are emerging as potentially important pharmacogenomic risk markers for aLQTS and could form part of personalized medicine approaches in the future.

Prevalence and clinical correlates of exercise-induced ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

Exercise has a deleterious effect on the phenotypic expression of arrhythmogenic right ventricular cardiomyopathy (ARVC) and increases the risk of sudden death. The aim of the study was to determine the prevalence and correlates of exercise-induced arrhythmias during exercise tolerance test (ETT) in patients with ARVC. Between 2010 and 2019, 30 (47% males, mean age 42 ± 12 years) consecutive patients with a definite diagnosis of ARVC underwent a full genotypic and phenotypic characterization at our center. Exercise-induced arrhythmic response (EIAR) was defined by the development of complex or repetitive ventricular arrhythmias after stage 2 of exercise. A heart rate ≥ 85% of predicted was achieved by 23 (77%) patients. In 16 (53%) cases, a desmosomal pathogenic variant was found [most commonly PKP2 (n = 7) and DSP (n = 3)]. In 12 (40%) cases, an EIAR was observed. In 2 (6%) patients, ETT was interrupted due to the onset of ventricular tachycardia (sustained with a LBBB/inferior axis pattern in one case, and non-sustained LBBB/superior axis pattern in the other). Mean body surface area (BSA)-indexed left ventricular (LV) end-diastolic volumes (EDV) were higher in the EIAR group (92 ± 12 ml/m2 vs 80 ± 7 ml/m2, p = 0.002), as well as right ventricular EDV/BSA (110 ± 18 ml/m2 vs 91 ± 27 ml/m2, p = 0.04). Subepicardial/mid-wall LV late gadolinium enhancement (LGE) was more common in the EIAR group (67% vs 22%, p = 0.01). ARVC patients commonly exhibit exercise-induced ventricular arrhythmias. Patients with more significant RV remodeling and LV involvement (based on the presence of LV dilatation and LGE) appear more susceptible to exercise-induced arrhythmias.

Cardiac magnetic resonance in patients with ARVC and family members: the potential role of native T1 mapping.

Left ventricular (LV) involvement in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is not evaluated in the revised Task Force Criteria, possibly leading to underdiagnosis. This study explored the diagnostic role of myocardial native T1 mapping in patients with ARVC and their first-degree relatives. Thirty ARVC patients (47% males, mean age 45 ± 27 years) and 59 first-degree relatives not meeting diagnostic criteria underwent CMR with native T1 mapping. C MR was abnormal in 26 (87%) patients with ARVC. The right ventricle was affected in isolation in 13 (43%) patients. Prior to T1 mapping assessment, 2 (7%) patients exhibited isolated LV involvement and 11 (36%) patients showed features of biventricular disease. Left ventricular involvement was manifest as detectable LV late gadolinium enhancement (LGE) in 12 out of 13 cases. According to pre-specified inter-ventricular septal (IVS) T1 mapping thresholds, 11 (37%) patients revealed raised native T1 values including 5 out of the 17 patients who would otherwise have been classified as exhibiting a normal LV by conventional imaging parameters. Native septal T1 values were elevated in 22 (37%) of the 59 first-degree relatives included. Biventricular involvement is commonly observed in ARVC; native myocardial T1 values are raised in more than one third of patients, including a significant proportion of cases that would have been otherwise classified as exhibiting a normal LV using conventional CMR techniques. The significance of abnormal T1 values in first-degree relatives at risk will need validation through longitudinal studies.

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.

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.

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.

Non-invasive assessment of ventriculo-arterial coupling using aortic wave intensity analysis combining central blood pressure and phase-contrast cardiovascular magnetic resonance.

BACKGROUND: Wave intensity analysis (WIA) in the aorta offers important clinical and mechanistic insight into ventriculo-arterial coupling, but is difficult to measure non-invasively. We performed WIA by combining standard cardiovascular magnetic resonance (CMR) flow-velocity and non-invasive central blood pressure (cBP) waveforms. METHODS AND RESULTS: Two hundred and six healthy volunteers (age range 21-73 years, 47% male) underwent sequential phase contrast CMR (Siemens Aera 1.5 T, 1.97 × 1.77 mm2, 9.2 ms temporal resolution) and supra-systolic oscillometric cBP measurement (200 Hz). Velocity (U) and central pressure (P) waveforms were aligned using the waveform foot, and local wave speed was calculated both from the PU-loop (c) and the sum of squares method (cSS). These were compared with CMR transit time derived aortic arch pulse wave velocity (PWVtt). Associations were examined using multivariable regression. The peak intensity of the initial compression wave, backward compression wave, and forward decompression wave were 69.5 ± 28, -6.6 ± 4.2, and 6.2 ± 2.5 × 104 W/m2/cycle2, respectively; reflection index was 0.10 ± 0.06. PWVtt correlated with c or cSS (r = 0.60 and 0.68, respectively, P < 0.01 for both). Increasing age decade and female sex were independently associated with decreased forward compression wave (-8.6 and -20.7 W/m2/cycle2, respectively, P < 0.01) and greater wave reflection index (0.02 and 0.03, respectively, P < 0.001). CONCLUSION: This novel non-invasive technique permits straightforward measurement of wave intensity at scale. Local wave speed showed good agreement with PWVtt, and correlation was stronger using the cSS than the PU-loop. Ageing and female sex were associated with poorer ventriculo-arterial coupling in healthy individuals.

KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.

BACKGROUNDThe presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown.METHODSTo identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry.RESULTSWe identified a genome-wide significant (P < 5 × 10-8) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, P = 7.7 × 10-12) but did not reveal additional loci. Colocalization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery.CONCLUSIONSIn this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies.FUNDINGThis project was funded by the German Center for Cardiovascular Research (DZHK Shared Expertise SE081 - STATS). For detailed funding information per study, see the Supplemental Acknowledgments.

Risk score for the exclusion of arrhythmic events in arrhythmogenic right ventricular cardiomyopathy at first presentation.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder associated with an increased risk of life-threatening arrhythmias in some patients. Risk stratification remains challenging. Therefore, we sought a non-invasive, easily applicable risk score to predict sustained ventricular arrhythmias in these patients. METHODS: Cohort of Patients who fulfilled the 2010 ARVC task force criteria were consecutively recruited. Detailed clinical data were collected at baseline and during follow up. The clinical endpoint was a composite of recurrent sustained ventricular arrhythmias and hospitalization due to ventricular arrhythmias. Multivariable logistic regression was used to develop models to predict the arrhythmic risk. A cohort including patients from other registries in UK, Canada and Switzerland was used as a validation population. RESULTS: One hundred and thirty-five patients were included of whom 35 patients (31.9%) reached the endpoint. A model consisting of filtered QRS duration on signal-averaged ECG, non-sustained VT (NSVT) on 24 h-ECG, and absence of negative T waves in lead aVR on 12­lead surface ECG was able to predict arrhythmic events with a sensitivity of 81.8%, specificity of 84.0% and a negative predictive value of 95.5% at the first presentation of the disease. This risk score was validated in international ARVC registry patients. CONCLUSION: A risk score consisting of a filtered QRS duration ≥117 ms, presence of NSVT on 24 h-ECG and absence of negative T waves in lead aVR was able to predict arrhythmic events at first presentation of the disease.

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.

The narrow-sense and common single nucleotide polymorphism heritability of early repolarization.

BACKGROUND: Early repolarization (ER) is a risk marker for sudden cardiac death. Higher risk is associated with horizontal/descending ST-segment ER in the inferior or inferolateral ECG leads. Studies in family cohorts have demonstrated substantial heritability for the ER pattern, but genome-wide association studies (GWAS) have failed to identify statistically significant and replicable genetic signals. METHODS AND RESULTS: We assessed the narrow-sense and common single nucleotide polymorphism (SNP) heritability of ER and ER subtypes using ECG data from 5829 individuals (TwinsUK, BRIGHT and GRAPHIC cohorts). ER prevalence was 8.3%. In 455 monozygous vs 808 dizygous twin pairs, concordances and twin correlations for ER subtypes (except horizontal/descending ST-segment ER) were higher and familial resemblance (except notched ER) was significant. Narrow-sense heritability estimates derived from 1263 female twin pairs using the structural equation program Mx ranged from 0.00-0.47 and common SNP heritability estimates derived from 4009 unrelated individuals of both sexes using Genome-wide Restricted Maximum Likelihood (GREML) ranged from 0.00-0.36, but none were statistically significant. CONCLUSION: From our data, ER shows limited genetic predisposition. There appears to be significant environmental influence and these modest narrow-sense and common SNP heritability estimates may explain why previous GWAS have been unsuccessful.

Pulmonary embolism and infarction with a paradoxical thrombus visualised in both atria.

A 59-year-old woman presented with a sudden onset of breathlessness and chest pain. An echocardiography and CT scan showed pulmonary embolism and infarction with a paradoxical thrombus visualised in both atria. For haemodynamically stable patients, the optimal management strategy is poorly defined. Three main strategies were considered: surgical thrombectomy, thrombolysis and anticoagulation. Surgery with reversal of anticoagulation may lead to further coagulation and increased risk of bleeding complications. The significant pulmonary hypertension and right ventricular infarction raised the prospect of difficult weaning from cardiopulmonary bypass following thrombectomy. Thrombolysis, which has significant mortality rate, and systemic embolisation including pulmonary infarction with haemorrhagic transformation were also contraindications. A multidisciplinary approach was adopted and anticoagulation was therefore believed to be the safest and effective approach. Here, the use of anticoagulation alone was fortunately successful but could as easily end in disaster. This approach should be considered the ideal paradigm to yield optimum outcomes.

The Diagnostic Yield of Brugada Syndrome After Sudden Death With Normal Autopsy.

BACKGROUND: Familial evaluation after a sudden death with negative autopsy (sudden arrhythmic death syndrome; SADS) may identify relatives at risk of fatal arrhythmias. OBJECTIVES: This study aimed to assess the impact of systematic ajmaline provocation testing using high right precordial leads (RPLs) on the diagnostic yield of Brugada syndrome (BrS) in a large cohort of SADS families. METHODS: Three hundred three SADS families (911 relatives) underwent evaluation with resting electrocardiogram using conventional and high RPLs, echocardiography, exercise, and 24-h electrocardiogram monitor. An ajmaline test with conventional and high RPLs was undertaken in 670 (74%) relatives without a familial diagnosis after initial evaluation. Further investigations were guided by clinical suspicion. RESULTS: An inherited cardiac disease was diagnosed in 128 (42%) families and 201 (22%) relatives. BrS was the most prevalent diagnosis (n = 85, 28% of families; n = 140, 15% of relatives). Ajmaline testing was required to unmask the BrS in 97% of diagnosed individuals. The use of high RPLs showed a 16% incremental diagnostic yield of ajmaline testing by diagnosing BrS in an additional 49 families. There were no differences of the characteristics between individuals and families with a diagnostic pattern in the conventional and the high RPLs. On follow-up, a spontaneous type 1 Brugada pattern and/or clinically significant arrhythmic events developed in 17% (n = 25) of the concealed BrS cohort. CONCLUSIONS: Systematic use of ajmaline testing with high RPLs increases substantially the yield of BrS in SADS families. Assessment should be performed in expert centers where patients are counseled appropriately for the potential implications of provocation testing.

Apical ballooning (takotsubo) syndrome with concurrent ST-segment elevation myocardial infarction.

We present the case of a 61-year-old woman admitted with chest pain and an ECG demonstrating ST-segment elevation in the lateral leads. Emergency coronary angiography demonstrated an occluded obtuse marginal branch. Percutaneous intervention was unsuccessful as the lesion could not be crossed with a wire. Left ventriculography and transthoracic echocardiography demonstrated hypokinesis of the entire apex but preserved contractility of the basal segments, consistent with a diagnosis of apical ballooning syndrome (ABS). Cardiac MRI demonstrated myocardial oedema in all mid to apical segments, with a left ventricular ejection fraction (LVEF) of 38%. Repeat study at 5 months demonstrated an infarct in the distribution of the occluded artery with late gadolinium enhancement, consistent with a diagnosis of a lateral wall myocardial infarction and an improvement in the LVEF to 51%. The case illustrates the novel observation that ABS and acute myocardial infarction may rarely occur simultaneously.

Anterior T-Wave Inversion in Young White Athletes and Nonathletes: Prevalence and Significance.

BACKGROUND: Anterior T-wave inversion (ATWI) on electrocardiography (ECG) in young white adults raises the possibility of cardiomyopathy, specifically arrhythmogenic right ventricular cardiomyopathy (ARVC). Whereas the 2010 European consensus recommendations for ECG interpretation in young athletes state that ATWI beyond lead V1 warrants further investigation, the prevalence and significance of ATWI have never been reported in a large population of asymptomatic whites. OBJECTIVES: This study investigated the prevalence and significance of ATWI in a large cohort of young, white adults including athletes. METHODS: Individuals 16 to 35 years of age (n = 14,646), including 4,720 females (32%) and 2,958 athletes (20%), were evaluated by using a health questionnaire, physical examination, and 12-lead ECG. ATWI was defined as T-wave inversion in ≥2 contiguous anterior leads (V1 to V4). RESULTS: ATWI was detected in 338 individuals (2.3%) and was more common in women than in men (4.3% vs. 1.4%, respectively; p < 0.0001) and more common among athletes than in nonathletes (3.5% vs. 2.0%, respectively; p < 0.0001). T-wave inversion was predominantly confined to leads V1 to V2 (77%). Only 1.2% of women and 0.2% of men exhibited ATWI beyond V2. No one with ATWI fulfilled diagnostic criteria for ARVC after further evaluation. During a mean follow-up of 23.1 ± 12.2 months none of the individuals with ATWI experienced an adverse event. CONCLUSIONS: ATWI confined to leads V1 to V2 is a normal variant or physiological phenomenon in asymptomatic white individuals without a relevant family history. ATWI beyond V2 is rare, particularly in men, and may warrant investigation.