Atrial fibrillation/atrial flutter related mortality trends in the US population 2010-2020: Regional, racial, sex variations.

BACKGROUND: There is an evolving need to evaluate atrial fibrillation/atrial flutter (AF/AFL) mortality trends across races, sexes, geographic regions and urbanization statuses to better understand management inequalities. METHODS: This observational study utilized the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database. Mortality rates due to AF/AFL as underlying and contributing causes of death between 2010 and 2020 were investigated. Mortality trends due to AF/AFL as contributing causes of death for different races, sexes, census regions and urbanization statuses were analyzed using annual percentage change (APC), and Joinpoint regression analysis. RESULTS: Mortality from AF/AFL as the underlying cause was increasing across the US until 2016 (APC 4.8%), followed by a plateau 2016-2020 (APC 0.0 %). Conversely, the mortality rate due to AF/AFL as a contributing cause increases 2010-2020 (APC 3.3%). The mortality rate in both sexes significantly increased in almost all groups, with the largest increase seen in Non-Hispanic Black males. Rural areas had a higher mortality rate (36.9 and 22.9 per 100,000 for males and females in 2020, respectively) and higher slope of increase than urban areas in total US population. Non-Hispanic White people had greater mortality than Non-Hispanic Black people; however, Non-Hispanic Black mortality rates are increasing at a faster rate in urban areas. CONCLUSION: AF/AFL as the underlying cause of death has plateaued from 2016 across the US 2010-2020; whilst AF/AFL as contributing cause of death is increasing. Significant discrepancies in mortality rates are identified between races and urbanization status.

An observational epidemiological study to analyze intracerebral hemorrhage across the United States: Incidence and mortality trends from 1990 to 2017.

OBJECTIVES: Intracerebral Hemorrhage (ICH) accounts for 10% of strokes annually in the United States (US). Up-to-date trends in disease burden and regional variations remain unknown. Our study reports updated trends of ICH incidence, mortality, and mortality to incidence ratio (MIR) across the US. MATERIALS AND METHODS: Observational study to evaluate the incidence and mortality from ICH across the US. Data was obtained from Global Burden of Disease (GBD) database. Age-Standardized Incidence (ASIRs) and Death (ASDRs) Rates, as well as the Mortality- to-Incidence ratios (MIRs) for ICH in the US overall and state-wise from 1990-2017. Joinpoint regression analysis was used, with presentation of estimated annual percentage changes (EAPCs). RESULTS: Overall decrease in ASIRs, ASDRs, and MIRs in the US for both sexes. The 2017 mean ASIR was 25.67/100,000 for men and 19.17/100,000 for women, whereas mean ASDR was 13.96/100,000 for men and 11.35/100,000 for women. District of Columbia had greatest decreases in ASIR EAPCs for both men and women at -41.25% and -40.58%, respectively, and greatest decreases in ASDR EAPCs for men and women at -55.38% and -48.51%, respectively. MIR between 1990-2017 decreased in men by -12.12% and women by -7.43%. MIR increased in men from 2014-2017 (EAPC +2.2%) and in women from 2011-2017 (EAPC +1.0%). CONCLUSION: Decreasing trends in incidence, mortality, and MIR. No significant trends in mortality were found in the last 6 years of the study period. MIR worsened in males from 2014-2017 and females from 2011-2017, suggesting decreased ICH-related survival lately.

Temporal pattern/episode duration-based classification of atrial fibrillation as paroxysmal vs. persistent: is it time to develop a more integrated prognostic score to optimize management?

Atrial fibrillation (AF) is a clinically heterogeneous arrhythmia that is currently classified according to the variety of temporal rhythm based manifestations observed clinically, including 'first detected episode', 'paroxysmal', 'persistent', or 'permanent' AF. Despite being widely adopted by the most recent consensus guidelines, the utility of this classification system to stratify patients into distinct and clinically useful groups that have different outcomes including mortality, morbidity, specific cardiovascular outcomes, and quality of life (QoL), remains questionable. This is particularly true regarding the distinction between paroxysmal and persistent AF. Here, we demonstrate there is limited and conflicting evidence that this distinction is useful in predicting mortality, morbidity (including stroke and heart failure), symptom burden and QoL, although there is convincing evidence that patients with paroxysmal AF have favourable outcomes following electrical cardioversion and have better ablation procedural outcomes. Risk stratification schemes including the CHA2DS2VASc score are widely used to help clinicians stratify patients at high risk of stroke, whilst a number of newer, potentially superior, competitors have also recently been developed. A range of parameters including left atrial (LA) size, LA morphology, LA fibrosis [assessed by magnetic resonance imaging (MRI)] LA appendage morphology and LA function (assessed by echo) have all been recently suggested to identify higher risk patients and may, perhaps in combination with validated risk stratification scores and emerging genetic data, provide clinicians with the information necessary to more accurately stratify patients to ensure better outcomes of specific AF treatments and prevent adverse events.

Quantification of both the area-at-risk and acute myocardial infarct size in ST-segment elevation myocardial infarction using T1-mapping.

BACKGROUND: A comprehensive cardiovascular magnetic resonance (CMR) in reperfused ST-segment myocardial infarction (STEMI) patients can be challenging to perform and can be time-consuming. We aimed to investigate whether native T1-mapping can accurately delineate the edema-based area-at-risk (AAR) and post-contrast T1-mapping and synthetic late gadolinium (LGE) images can quantify MI size at 1.5 T. Conventional LGE imaging and T2-mapping could then be omitted, thereby shortening the scan duration. METHODS: Twenty-eight STEMI patients underwent a CMR scan at 1.5 T, 3 ± 1 days following primary percutaneous coronary intervention. The AAR was quantified using both native T1 and T2-mapping. MI size was quantified using conventional LGE, post-contrast T1-mapping and synthetic magnitude-reconstructed inversion recovery (MagIR) LGE and synthetic phase-sensitive inversion recovery (PSIR) LGE, derived from the post-contrast T1 maps. RESULTS: Native T1-mapping performed as well as T2-mapping in delineating the AAR (41.6 ± 11.9% of the left ventricle [% LV] versus 41.7 ± 12.2% LV, P = 0.72; R2 0.97; ICC 0.986 (0.969-0.993); bias -0.1 ± 4.2% LV). There were excellent correlation and inter-method agreement with no bias, between MI size by conventional LGE, synthetic MagIR LGE (bias 0.2 ± 2.2%LV, P = 0.35), synthetic PSIR LGE (bias 0.4 ± 2.2% LV, P = 0.060) and post-contrast T1-mapping (bias 0.3 ± 1.8% LV, P = 0.10). The mean scan duration was 58 ± 4 min. Not performing T2 mapping (6 ± 1 min) and conventional LGE (10 ± 1 min) would shorten the CMR study by 15-20 min. CONCLUSIONS: T1-mapping can accurately quantify both the edema-based AAR (using native T1 maps) and acute MI size (using post-contrast T1 maps) in STEMI patients without major cardiovascular risk factors. This approach would shorten the duration of a comprehensive CMR study without significantly compromising on data acquisition and would obviate the need to perform T2 maps and LGE imaging.

Trends in the incidence and mortality of infective endocarditis in high-income countries between 1990 and 2019.

BACKGROUND: Infective endocarditis (IE) remains a life-threatening disease with high morbidity and mortality. OBJECTIVES: To describe temporal trends in IE incidence, mortality and survival over the last 30 years. METHODS: Nineteen high-income countries (the 'EU 15+') were included. Age-standardised and sex-stratified incidence rates (ASIRs) and mortality rates (ASMRs) for IE were extracted from the Global Burden of Disease (GBD) database between 1990 and 2019, and mortality to incidence ratios (ASMIRs) were calculated. Trends were analysed using Joinpoint regression analysis. RESULTS: ASIRs were higher in males than females and increased in both sexes in all countries between 1990 and 2019. A recent steep rise in ASIRs was noted in several countries including the UK, the USA and Germany. ASMRs increased for both sexes in all countries except Finland and Austria. The largest increase in ASMR was observed in females in Italy (+246%). ASMIRs were generally higher in females compared to males, with large increases in ASMIRs (indicating worsening survival) at the end of the 20th century, but more recent stabilisation or decline across the study cohort. CONCLUSIONS: While the incidence and mortality of IE have increased over the last 30 years, recent data suggest that these trends have plateaued or reversed in most countries studied. However, a recent surge in incidence in several countries (including the USA and UK) is of concern, while unfavourable outcomes in females also merit attention. More encouragingly, this analysis provides the first indication of improving IE survival at population level, supporting recent advances in diagnosis and treatment.

Demographic and State-Level Trends in Mortality Due to Ischemic Heart Disease in the United States from 1999 to 2019.

Although there have been advances in ischemic heart disease (IHD) care, variation in IHD-related mortality trends across the United States has not been well described. We used the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research database to evaluate variation in IHD-related mortality for demographic groups in the United States between 1999 and 2019. Age-adjusted mortality rates (AAMRs) were stratified by gender, race, Hispanic ethnicity, and US state. Crude mortality rates were evaluated using 10-year age groups. IHD-related AAMRs decreased from 195 to 88 per 100,000 nationally, with slower a decrease from 2010 to 2019 (average annual percent change [AAPC] -2.6% [95% confidence interval -2.9% to -2.2%]) compared with 2002 to 2010 (AAPC -5.3% [95% confidence interval -5.6% to -4.9%]). All groups had decreases in AAMRs, although Black populations persistently had the highest AAMR, and women had greater relative decreases than men. AAPC was -3.7% for White men, -4.7% for White women, -3.9% for Black men, -4.9% for Black women, -4.1% for Hispanic men, and -5.1% for Hispanic women. Populations ≥65 years had greater relative mortality decreases than populations <65 years. The median AAMR (2019) and AAPC (1999 to 2019) across states was 86 (range 58 to 134) and -3.8% (range -1.7% to -4.8%), respectively. In conclusion, declines in IHD-related mortality have slowed in the United States, with a significant geographic variation. Black populations persistently had the highest AAMRs, and decreases were relatively greater for women and populations ≥65 years. The impact of demographics and geography on IHD should be further explored and addressed as part of public health measures.

Temporal trend analysis of rheumatic heart disease burden in high-income countries between 1990 and 2019.

AIMS: To assesses trends in rheumatic heart disease (RHD) burden in high-income, European Union 15+ (EU15+) countries between 1990 and 2019. METHODS AND RESULTS: Cross-sectional analysis of the incidence and mortality of RHD was conducted using data from the Global Burden of Disease Study (GBD) database. Age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were extracted for EU15 + countries per sex for each of the years from 1990-2019, inclusive, and mortality-to-incidence indices (MII) were computed. Joinpoint regression analysis was used for the description of trends. Over 29 years, an overall declining trend in RHD incidence and mortality across EU 15 + nations were observed. There was significant variability in RHD incidence and mortality rates across high-income countries. However, both RHD incidence and mortality were higher among females compared to males across EU15 + countries over the observed period. The most recent incidence trend, starting predominantly after 2014, demonstrated a rise in RHD incidence in most countries for both sexes. The timing of this RHD resurgence corresponds temporally with an influx of migrants and refugees into Europe. The recent increasing RHD incidence rates ranged from + 0.4% to + 24.7% for males, and + 0.6% to + 11.4% for females. CONCLUSIONS: More than half of EU15 + nations display a recent increase in RHD incidence rate across both sexes. Possible factors associated with this rise are discussed and include increase in global migration from nations with higher RHD prevalence, host nation factors such as migrants' housing conditions, healthcare access and migrant health status on arrival.

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.

Imaging Pericytes and the Regulation of Cerebral Blood Flow.

The brain's high energy requirements drive the need for close coupling of local neuronal activity to blood supply. Capillaries have been shown to dilate before arterioles in response to sensory stimulation, pointing to a key role for microvascular pericytes in mediating cerebrovascular dynamics. However, many aspects of these cells' function remain unknown and even controversial, from their identification, to the mechanism and regulation of their contractility in physiology and disease. Investigating how pericytes regulate vascular diameter is therefore likely to be the subject of many future experiments. Here we provide protocols for three different techniques (ex vivo slice imaging, in vivo imaging, and immunohistochemistry) that are highly valuable for performing such experiments.

Utility of wearable physical activity monitors in cardiovascular disease: a systematic review of 11 464 patients and recommendations for optimal use.

Aims: Physical activity (PA) plays an important role in primary and secondary prevention of cardiovascular disease (CVD), functioning as a marker of disease progression and response to therapy. Real-world measurement of habitual PA is now possible through wearable activity monitors, however, their use in cardiovascular patients is not well described. Methods and results: We performed a systematic review to summarize how wearable activity monitors have been used to measure PA in patients with CVD, with 11 464 patients included across 108 studies. Activity monitors were primarily used in the setting of cardiac rehabilitation (46, 43%). Most often, triaxial accelerometers (70, 65%) were instructed to be worn at the hip (58, 54%) for 7 days (n = 54, 50%). Thirty-nine different activity monitors were used, with a range of accelerometer specific settings for collection and reporting of activity data. Activity was reported most commonly as time spent in metabolic equivalent-defined activity levels (49, 45%), while non-wear time was defined in just 16 (15%) studies. Conclusion: The collecting, processing, and reporting of accelerometer-related outcomes were highly heterogeneous. Most validation studies are limited to healthy young adults, while the paucity of methodological information disclosed renders interpretation of results and cross-study comparison challenging. While accelerometers are promising tools to measure real-world PA, we highlight current challenges facing their use in elderly multimorbid cardiology patients. We suggest recommendations to guide investigators using these devices in cardiovascular research. Future work is required to determine optimal methodology and consensus-based development of meaningful outcomes using raw acceleration data.

Trends in Mortality From Aortic Stenosis in Europe: 2000-2017.

Background: Trends in mortality from aortic stenosis across European countries are not well-understood, especially given the significant growth in transcatheter aortic valve implantation (TAVI) in the last 10 years. Methods: Age-standardised death rates were extracted from the World Health Organisation Mortality Database, using the International Classification of Diseases 10th edition code for non-rheumatic aortic stenosis for those aged > 45 years between 2000 and 2017. The UK and countries from the European Union with at least 1,000,000 inhabitants and at least 50% available datapoints over the study period were included: a total of 23 countries. Trends were described using Joinpoint regression analysis. Results: No reductions in mortality were demonstrated across all countries 2000-2017. Large increases in mortality were found for Croatia, Poland and Slovakia for both sexes (>300% change). Mortality plateaued in Germany from 2008 in females and 2012 in males, whilst mortality in the Netherlands declined for both sexes from 2007. Mortality differences between the sexes were observed, with greater mortality for males than females across most countries. Conclusions: Mortality from aortic stenosis has increased across Europe from 2000 to 2017. There are, however, sizable differences in mortality trends between Eastern and Western European countries. The need for health resource planning strategies to specifically target AS, particularly given the expected increase with ageing populations, is highlighted.

Gradual Not Sudden Change: Multiple Sites of Functional Transition Across the Microvascular Bed.

In understanding the role of the neurovascular unit as both a biomarker and target for disease interventions, it is vital to appreciate how the function of different components of this unit change along the vascular tree. The cells of the neurovascular unit together perform an array of vital functions, protecting the brain from circulating toxins and infection, while providing nutrients and clearing away waste products. To do so, the brain's microvasculature dilates to direct energy substrates to active neurons, regulates access to circulating immune cells, and promotes angiogenesis in response to decreased blood supply, as well as pulsating to help clear waste products and maintain the oxygen supply. Different parts of the cerebrovascular tree contribute differently to various aspects of these functions, and previously, it has been assumed that there are discrete types of vessel along the vascular network that mediate different functions. Another option, however, is that the multiple transitions in function that occur across the vascular network do so at many locations, such that vascular function changes gradually, rather than in sharp steps between clearly distinct vessel types. Here, by reference to new data as well as by reviewing historical and recent literature, we argue that this latter scenario is likely the case and that vascular function gradually changes across the network without clear transition points between arteriole, precapillary arteriole and capillary. This is because classically localized functions are in fact performed by wide swathes of the vasculature, and different functional markers start and stop being expressed at different points along the vascular tree. Furthermore, vascular branch points show alterations in their mural cell morphology that suggest functional specializations irrespective of their position within the network. Together this work emphasizes the need for studies to consider where transitions of different functions occur, and the importance of defining these locations, in order to better understand the vascular network and how to target it to treat disease.

Incidence and Mortality Trends of Atrial Fibrillation/Atrial Flutter in the United States 1990 to 2017.

Atrial fibrillation (AF) and flutter (AFL) are the most common clinically significant arrhythmias in older adults with an increasing disease burden due to an aging population. However, up-to-date trends in disease burden and regional variation remain unknown. In an observational study utilizing the Global Burden of Disease (GBD) database, age-standardized mortality and incidence rates for AF overall and for each state in the United States (US) from 1990 to 2017 were determined. All analyses were stratified by gender. The relative change in age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) over the observation period were determined. Trends were analyzed using Joinpoint regression analysis. The mean ASIR per 100,000 population for men was 92 (+/-8) and for women was 62 (+/-5) in the US in 2017. The mean ASDR per 100,000 population for men was 5.8 (+/-0.3) and for women was 4.4 (+/-0.4). There were progressive increases in ASIR and ASDR in all but 1 state. The states with the greatest percentage change in incidence were New Hampshire (+13.5%) and Idaho (+16.0%) for men and women, respectively. The greatest change regarding mortality was seen in Mississippi (+26.3%) for men and Oregon (+53.8%) for women. In conclusion these findings provide updated evidence of increasing AF and/or AFL incidence and mortality on a national and regional level in the US, with women experiencing greater increases in incidence and mortality rates. This study demonstrates that the public health burden related to AF in the United States is progressively worsening but disproportionately across states and among women.

Baseline NT-proBNP Accurately Predicts Symptom Response to Transcatheter Aortic Valve Implantation.

Background Up to 30% of patients undergoing transcatheter aortic valve implantation (TAVI) experience minimal symptomatic benefit or die within 1 year, indicating an urgent need for enhanced patient selection. Previous analyses of baseline NT-proBNP (N-terminal pro-brain natriuretic peptide) and TAVI outcomes have assumed a linear relationship, yielding conflicting results. We reexamined the relationship between baseline NT-proBNP and symptomatic improvement after TAVI. Methods and Results Symptom status, clinical and echocardiographic data, and baseline NT-proBNP were reviewed from 144 consecutive patients undergoing TAVI for severe symptomatic aortic stenosis. The primary end point was change in New York Heart Association functional class at 1 year. There was a nonlinear, inverted-U relationship between log-baseline NT-proBNP and post-TAVI change in NYHA class (R2=0.4559). NT-proBNP thresholds of <800 and >10 000 ng/L accurately predicted no symptomatic improvement at 1 year (sensitivity 88%, specificity 83%, positive predictive value 72%, negative predictive value 93%). In adjusted analyses, baseline NT-proBNP outside this "sweet-spot" range was the only factor independently associated with poor functional outcome (high: NT-proBNP >10 000 ng/L, odds ratio [OR], 65; 95% CI, 6-664; low: NT-proBNP <800 ng/L, OR, 73; 95% CI, 7-738). Conclusions Baseline NT-proBNP is a useful prognostic marker to predict poor symptom relief after TAVI and may indicate when intervention is likely to be futile. Both low (<800 ng/L) and very high (>10 000 ng/L) levels are strongly associated with poor functional outcome, suggesting an alternative cause for symptoms in the former scenario and an irrevocably diseased left ventricle in the latter. Further evaluation of this relationship is warranted.

Myocarditis mimicking acute aortic dissection.

We report a case of myocarditis that closely mimicked acute aortic dissection in a young woman. The initial presentation was with sudden onset severe back pain and chest discomfort, associated with bilateral arm paraesthesia. The initial ECG demonstrated inferior ST-segment elevation with reciprocal anterior changes. The diagnosis was facilitated by urgent echocardiography, a CT aortogram and invasive coronary angiography to exclude aortic dissection and myocardial infarction, respectively. Acute myocarditis was later confirmed on cardiac MRI. The patient was treated conservatively with no subsequent arrhythmias with preservation of biventricular function.

Myocardial Infarct Size by CMR in Clinical Cardioprotection Studies: Insights From Randomized Controlled Trials.

OBJECTIVES: The aim of this study was to review randomized controlled trials (RCTs) using cardiac magnetic resonance (CMR) to assess myocardial infarct (MI) size in reperfused patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: There is limited guidance on the use of CMR in clinical cardioprotection RCTs in patients with STEMI treated by primary percutaneous coronary intervention. METHODS: All RCTs in which CMR was used to quantify MI size in patients with STEMI treated with primary percutaneous coronary intervention were identified and reviewed. RESULTS: Sixty-two RCTs (10,570 patients, January 2006 to November 2016) were included. One-third did not report CMR vendor or scanner strength, the contrast agent and dose used, and the MI size quantification technique. Gadopentetate dimeglumine was most commonly used, followed by gadoterate meglumine and gadobutrol at 0.20 mmol/kg each, with late gadolinium enhancement acquired at 10 min; in most RCTs, MI size was quantified manually, followed by the 5 standard deviation threshold; dropout rates were 9% for acute CMR only and 16% for paired acute and follow-up scans. Weighted mean acute and chronic MI sizes (≤12 h, initial TIMI [Thrombolysis in Myocardial Infarction] flow grade 0 to 3) from the control arms were 21 ± 14% and 15 ± 11% of the left ventricle, respectively, and could be used for future sample-size calculations. Pre-selecting patients most likely to benefit from the cardioprotective therapy (≤6 h, initial TIMI flow grade 0 or 1) reduced sample size by one-third. Other suggested recommendations for standardizing CMR in future RCTs included gadobutrol at 0.15 mmol/kg with late gadolinium enhancement at 15 min, manual or 6-SD threshold for MI quantification, performing acute CMR at 3 to 5 days and follow-up CMR at 6 months, and adequate reporting of the acquisition and analysis of CMR. CONCLUSIONS: There is significant heterogeneity in RCT design using CMR in patients with STEMI. The authors provide recommendations for standardizing the assessment of MI size using CMR in future clinical cardioprotection RCTs.

Capillary pericytes mediate coronary no-reflow after myocardial ischaemia.

After cardiac ischaemia, a prolonged decrease of coronary microvascular perfusion often occurs even after flow is restored in an upstream artery. This 'no-reflow' phenomenon worsens patient prognosis. In the brain, after stroke, a similar post-ischaemic 'no-reflow' has been attributed to capillary constriction by contractile pericytes. We now show that occlusion of a rat coronary artery, followed by reperfusion, blocks 40% of cardiac capillaries and halves perfused blood volume within the affected region. Capillary blockages colocalised strongly with pericytes, where capillary diameter was reduced by 37%. The pericyte relaxant adenosine increased capillary diameter by 21% at pericyte somata, decreased capillary block by 25% and increased perfusion volume by 57%. Thus, cardiac pericytes constrict coronary capillaries and reduce microvascular blood flow after ischaemia, despite re-opening of the culprit artery. Cardiac pericytes are therefore a novel therapeutic target in ischaemic heart disease.

Exercise restrictions for patients with inherited cardiac conditions: Current guidelines, challenges and limitations.

Inherited primary arrhythmia syndromes are a clinically heterogeneous group of relatively uncommon but important inherited cardiac conditions that are associated with an increased risk of sudden cardiac death (SCD) in the setting of a structurally normal heart. These include long-QT syndrome (LQTS), Short-QT syndrome (SQTS), Brugada syndrome (BrS) and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The cardiomyopathies represent the other major group of inherited cardiac conditions associated with SCD, of which hypertrophic cardiomyopathy (HCM) is the most common. Exercise is a known trigger of ventricular arrhythmias in many of these conditions, however marked genetic and clinical heterogeneity within individual diseases means that certain patients are at a much greater risk of lethal ventricular arrhythmias during exercise than others. For instance, LQTS type 1 (LQT1) and CPVT patients are at particular risk during exertion, whilst in patients with other genetic variants of LQTS, BrS and SQTS, alternative triggers are more significant precipitants. Many channelopathy (principally Brugada, CPVT) & cardiomyopathy (mainly HCM) patients receive primary or secondary prevention therapy with an implantable cardiac defibrillator (ICD). Exercising with an ICD in situ carries a range of additional risks including inappropriate shocks and lead complications. This review will focus on the risk of exercise-induced SCD in patients with inherited cardiac conditions, the current clinical guidelines in this area and the special consideration of patients with an ICD.