International External Validation Study of the 2014 European Society of Cardiology Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-HCM).

BACKGROUND: Identification of people with hypertrophic cardiomyopathy (HCM) who are at risk of sudden cardiac death (SCD) and require a prophylactic implantable cardioverter defibrillator is challenging. In 2014, the European Society of Cardiology proposed a new risk stratification method based on a risk prediction model (HCM Risk-SCD) that estimates the 5-year risk of SCD. The aim was to externally validate the 2014 European Society of Cardiology recommendations in a geographically diverse cohort of patients recruited from the United States, Europe, the Middle East, and Asia. METHODS: This was an observational, retrospective, longitudinal cohort study. RESULTS: The cohort consisted of 3703 patients. Seventy three (2%) patients reached the SCD end point within 5 years of follow-up (5-year incidence, 2.4% [95% confidence interval {CI}, 1.9-3.0]). The validation study revealed a calibration slope of 1.02 (95% CI, 0.93-1.12), C-index of 0.70 (95% CI, 0.68-0.72), and D-statistic of 1.17 (95% CI, 1.05-1.29). In a complete case analysis (n= 2147; 44 SCD end points at 5 years), patients with a predicted 5-year risk of <4% (n=1524; 71%) had an observed 5-year SCD incidence of 1.4% (95% CI, 0.8-2.2); patients with a predicted risk of ≥6% (n=297; 14%) had an observed SCD incidence of 8.9% (95% CI, 5.96-13.1) at 5 years. For every 13 (297/23) implantable cardioverter defibrillator implantations in patients with an estimated 5-year SCD risk ≥6%, 1 patient can potentially be saved from SCD. CONCLUSIONS: This study confirms that the HCM Risk-SCD model provides accurate prognostic information that can be used to target implantable cardioverter defibrillator therapy in patients at the highest risk of SCD.

Routine use of fluoroscopic guidance and up-front femoral angiography results in reduced femoral complications in patients undergoing coronary angiographic procedures: an observational study using an Interrupted Time-Series analysis.

Transradial access is increasingly used for coronary angiography and percutaneous coronary intervention, however, femoral access remains necessary for numerous procedures, including complex high-risk interventions, structural procedures, and procedures involving mechanical circulatory support. Optimising the safety of this approach is crucial to minimize costly and potentially life-threatening complications. We initiated a quality improvement project recommending routine fluoroscopic guidance (femoral head), and upfront femoral angiography should be performed to assess for location and immediate complications. We assessed the effect of these measures on the rate of vascular complications. Data were collected prospectively on 4534 consecutive patients undergoing femoral coronary angiographic procedures from 2015 to 2017. The primary end-point was any access complication. Outcomes were compared pre and post introduction including the use of an Interrupted Time-Series (ITS) analysis. 1890 patients underwent angiography prior to the introduction of routine fluoroscopy and upfront femoral angiography and 2644 post. All operators adopted these approaches. Baseline characteristics, including large sheath use, anticoagulant use and PCI rates were similar between the 2 groups. Fluoroscopy-enabled punctures were made in the 'safe zone' in over 91% of cases and upfront femoral angiography resulted in management changes i.e. procedural abandonment prior to heparin administration in 21 patients (1.1%). ITS analysis demonstrated evidence of a reduction in femoral complication rates after the introduction of the intervention, which was over and above the existing trend before the introduction (40% decrease RR 0.58; 95% CI: 0.25-0.87; P < 0.01). Overall these quality improvement measures were associated with a significantly lower incidence of access site complications (0.9% vs. 2.0%, P < 0.001). Routine fluoroscopy guided vascular access and upfront femoral angiography prior to anticoagulation leads to lower vascular complication rates. Thus, study shows that femoral intervention can be performed safely with very low access-related complication rates when fluoroscopic guidance and upfront angiography is used to obtain femoral arterial access.

Almanac 2014: cardiomyopathies.

Cardiomyopathies are myocardial disorders that are not explained by abnormal loading conditions and coronary artery disease. They are classified into a number of morphological and functional phenotypes that can be caused by genetic and non-genetic mechanisms. The dominant themes in papers published in 2012-2013 are similar to those reported in Almanac 2011, namely, the use (and interpretation) of genetic testing, development and application of novel non-invasive imaging techniques and use of serum biomarkers for diagnosis and prognosis. An important innovation since the last Almanac is the development of more sophisticated models for predicting adverse clinical events.

An Observational Study Assessing the Predictors of Procedural Failure From the Radial Approach: Is Right Radial Access Always the Best?

OBJECTIVE: The study aimed to determine the predictors of procedural failure (coronary cannulation) in patients undergoing coronary angiography ± percutaneous coronary intervention (PCI) from the transradial (TR) approach. METHODS: We conducted an observational study of 20,315 consecutive patients undergoing TR angiography between 2016 and 2020. TR failure was described as inability to cannulate the coronary arteries. Univariate and multivariate analyses were performed to determine independent predictors of TR failure. RESULTS: Out of the study population, TR failure was observed in 365 (1.8%) patients, out of which 281 (77%) crossed over successfully to the transfemoral (TF) route and 84 (23%) to left radial access (LRA). Unsuccessful procedures were most likely seen in patients who were elderly, female, BAME background, short stature or with a history of hypertension, diabetes, and renal disease. On regression analysis, age (OR: 1.024; 95% Cl: 1.014-1.035), female gender (OR: 0.729; 95% Cl: 0.555-0.957), BAME (OR: 0.786; 95% Cl: 0.612-0.959), height (OR: 0.988; 95% Cl: 0.977-0.999), hypertension (OR: 1.510; 95% Cl: 1.147-1.987) and RRA (OR: 1.977; 95% Cl: 1.105-3.538) were independent predictors of TR failure. On further analysis, these predictors of failure were not seen from the LRA approach. CONCLUSION: This study identifies that rates of TR failure are low and that predictors of failure differ between the RRA and LRA. The difference in predictors between the 2 routes suggests that in patients when coronary cannulation is unsuccessful via the RRA then the LRA could be considered as a second access site. Further study is needed to see if in selected patient groups the LRA could be used as the first-choice access route.

Is This the Prime Time for Transradial Access Left Ventricular Endomyocardial Biopsy?

Left ventricular endomyocardial biopsy (EMB) is an essential tool in the management of myocarditis and is conventionally performed via transfemoral access (TFA). Transradial access EMB (TRA-EMB) is a novel alternative and the authors sought to determine its safety and feasibility by conducting a systematic review of the literature. Medline was searched in 2020, and cohort demographics, procedural details and complications were extracted from selected studies. Four observational studies with a combined total of 496 procedures were included. TRA-EMB was most frequently performed with a sheathless MP1 guide catheter via the right radial artery. The most common complication was pericardial effusion (up to 11% in one study), but pericardial drainage for tamponade was rare (one reported case). Death and mitral valve damage have not been reported. TRA-EMB was successful in obtaining samples in 99% of reported procedures. The authors concluded that TRA-EMB is a safe and feasible alternative to TFA-EMB and the most common complication is uncomplicated pericardial effusion.

Early Hospital Discharge Following PCI for Patients With STEMI.

BACKGROUND: Regional heart attack services have improved clinical outcomes following ST-segment elevation myocardial infarction (STEMI) by facilitating early reperfusion by primary percutaneous coronary intervention (PCI). Early discharge after primary PCI is welcomed by patients and increases efficiency of health care. OBJECTIVES: This study aimed to assess the safety and feasibility of a novel early hospital discharge pathway for low-risk STEMI patients. METHODS: Between March 2020 and June 2021, 600 patients who were deemed at low risk for early major adverse cardiovascular events (MACE) were selected for inclusion in the pathway and were successfully discharged in <48 hours. Patients were reviewed by a structured telephone follow-up at 48 hours after discharge by a cardiac rehabilitation nurse and underwent a virtual follow-up at 2, 6, and 8 weeks and at 3 months. RESULTS: The median length of hospital stay was 24.6 hours (interquartile range [IQR]: 22.7-30.0 hours) (prepathway median: 65.9 hours [IQR: 48.1-120.2 hours]). After discharge, all patients were contacted, with none lost to follow-up. During median follow-up of 271 days (IQR: 88-318 days), there were 2 deaths (0.33%), both caused by coronavirus disease 2019 (>30 days after discharge), with 0% cardiovascular mortality and MACE rates of 1.2%. This finding compared favorably with a historical group of 700 patients meeting pathway criteria who remained in the hospital for >48 hours (>48-hour control group) (mortality, 0.7%; MACE, 1.9%) both in unadjusted and propensity-matched analyses. CONCLUSIONS: Selected low-risk patients can be discharged safely following successful primary PCI by using a pathway that is supported by a structured, multidisciplinary virtual follow-up schedule.

High Thrombus Burden in Patients With COVID-19 Presenting With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is thought to predispose patients to thrombotic disease. To date there are few reports of ST-segment elevation myocardial infarction (STEMI) caused by type 1 myocardial infarction in patients with COVID-19. OBJECTIVES: The aim of this study was to describe the demographic, angiographic, and procedural characteristics alongside clinical outcomes of consecutive cases of COVID-19-positive patients with STEMI compared with COVID-19-negative patients. METHODS: This was a single-center, observational study of 115 consecutive patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention at Barts Heart Centre between March 1, 2020, and May 20, 2020. RESULTS: Patients with STEMI presenting with concurrent COVID-19 infection had higher levels of troponin T and lower lymphocyte count, but elevated D-dimer and C-reactive protein. There were significantly higher rates of multivessel thrombosis, stent thrombosis, higher modified thrombus grade post first device with consequently higher use of glycoprotein IIb/IIIa inhibitors and thrombus aspiration. Myocardial blush grade and left ventricular function were significantly lower in patients with COVID-19 with STEMI. Higher doses of heparin to achieve therapeutic activated clotting times were also noted. Importantly, patients with STEMI presenting with COVID-19 infection had a longer in-patient admission and higher rates of intensive care admission. CONCLUSIONS: In patients presenting with STEMI and concurrent COVID-19 infection, there is a strong signal toward higher thrombus burden and poorer outcomes. This supports the need for establishing COVID-19 status in all STEMI cases. Further work is required to understand the mechanism of increased thrombosis and the benefit of aggressive antithrombotic therapy in selected cases.

The Safety and Feasibility of Transitioning From Transfemoral to Transradial Access Left Ventricular Endomyocardial Biopsy.

BACKGROUND: Left ventricular endomyocardial biopsy (LVEMB) is commonly performed via the transfemoral route. Radial access may help reduce vascular access complications, but there are few data on the safety and feasibility of transradial LVEMB. OBJECTIVE: Describe the safety and feasibility of transitioning from transfemoral to transradial access LVEMB. METHODS: This is a single-center, prospective, observational cohort study. Fifty procedures in 49 patients were included, 25 (50%) via the femoral route and 25 (50%) via the radial route. RESULTS: The cohort had a mean age of 47 ± 13 years and the most common indication for LVEMB was myocarditis. From June 2015 until September 2016, all procedures (n = 21) were performed via the femoral approach; thenceforth, there was a gradual transition to the radial approach. More tissue samples were obtained when the procedure was performed via the femoral approach (P<.01). The minimum sampling target of 3 specimens was not met in 4 patients (16%) via the radial approach and in 1 patient (4%) via the femoral approach. Complications occurred in 3/25 transradial procedures (12%; 2 cardiac perforations and 1 forearm hematoma) and 3/25 transfemoral procedures (12%; 1 cardiac perforation, 1 femoral artery pseudoaneurysm, and 1 ventricular fibrillation). Cardiac perforations via the transradial approach occurred during the early transition period. There were no deaths. CONCLUSIONS: Transradial LVEMB is feasible, with a similar complication profile to femoral procedures, but associated with a smaller number of specimens. Transitioning from transfemoral to transradial procedures may initially be associated with a higher risk of complications and potentially a lower diagnostic yield.

Computed tomography cardiac angiography for planning invasive angiographic procedures in patients with previous coronary artery bypass grafting.

AIMS: Invasive coronary angiography (ICA) is more complex and challenging in patients with previous coronary artery bypass grafts (CABG). Computed tomography coronary angiography (CTCA) may provide useful information prior to ICA to improve these procedures. This study aimed to see if upfront CTCA prior to coronary angiography can reduce contrast load, procedural duration, and procedural complications compared to ICA alone. METHODS AND RESULTS: This single-centre observational study included 835 patients with prior CABG undergoing invasive coronary angiography. One hundred and six patients underwent CTCA prior to ICA and were compared to 729 patients undergoing conventional coronary angiography alone (control group). No significant differences were seen between the two groups in patient demographics and procedural characteristics (number of bypass grafts), and interventional cardiologists' experience. The CTCA group had lower contrast volumes (171.3 vs 287.4 ml, p<0.0001), radiation doses (effective dose 4.6 vs 10.5 mSv, p<0.0001) and procedure times (fluorosocopy time 9.5 vs 12.6 min, p<0.0001) at the time of ICA compared to patients who did not have prior CTCA. Combined radiation doses (ICA+CTCA) versus ICA alone were similar (p=0.867) with significant reductions in overall contrast used seen in the CTCA group (p=0.005). Complete diagnostic studies were performed in all patients with prior CTCA (106 patients, 100%) compared to 543 patients (74.64%, p=<0.0001) without previous CTCA. As a result, 34 patients (4.4%) went on to have CTCA post angiography due to missed grafts. Of these, four needed further invasive angiographic assessment and subsequent coronary intervention following the CTCA scan. CONCLUSIONS: Prior CTCA improves graft detection at the time of coronary angiography and reduces the time necessary to localise graft ostium, the total procedure time, and volume of contrast media used.

Effectiveness of the 2014 European Society of Cardiology guideline on sudden cardiac death in hypertrophic cardiomyopathy: a systematic review and meta-analysis.

OBJECTIVE: In 2014, the European Society of Cardiology (ESC) recommended the use of a novel risk prediction model (HCM Risk-SCD) to guide use of implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We sought to determine the performance of HCM Risk-SCD by conducting a systematic review and meta-analysis of articles reporting on the prevalence of SCD within 5 years of evaluation in low, intermediate and high-risk patients as defined by the 2014 guidelines (predicted risk <4%, 4%-<6% and ≥6%, respectively). METHODS: The protocol was registered with PROSPERO (registration number: CRD42017064203). MEDLINE and manual searches for papers published from October 2014 to December 2017 were performed. Longitudinal, observational cohorts of unselected adult patients, without history of cardiac arrest were considered. The original HCM Risk-SCD development study was included a priori. Data were pooled using a random effects model. RESULTS: Six (0.9%) out of 653 independent publications identified by the initial search were included. The calculated 5-year risk of SCD was reported in 7291 individuals (70% low, 15% intermediate; 15% high risk) with 184 (2.5%) SCD endpoints within 5 years of baseline evaluation. Most SCD endpoints (68%) occurred in patients with an estimated 5-year risk of ≥4% who formed 30% of the total study cohort. Using the random effects method, the pooled prevalence of SCD endpoints was 1.01% (95% CI 0.52 to 1.61) in low-risk patients, 2.43% (95% CI 1.23 to 3.92) in intermediate and 8.4% (95% CI 6.68 to 10.25) in high-risk patients. CONCLUSIONS: This meta-analysis demonstrates that HCM Risk-SCD provides accurate risk estimations that can be used to guide ICD therapy in accordance with the 2014 ESC guidelines. REGISTRATION NUMBER: PROSPERO CRD42017064203;Pre-results.

Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records.

INTRODUCTION: To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. METHODS: Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997-2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. RESULTS: Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67-43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69-10.85]), heart failure (4.31, [3.30-5.62]), and atrial fibrillation (3.80 [3.04-4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27-2.84]) and coronary revascularisation (2.32 [1.46-3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. CONCLUSIONS: Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases.

Long-term outcomes for different surgical strategies to treat left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

AIMS: Surgical intervention is used to treat dynamic left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy. This study assesses the effect of different surgical strategies on long-term mortality and morbidity. METHODS AND RESULTS: In total, 347 patients underwent surgical intervention for LVOTO (1988-2015). Group A (n = 272) underwent septal myectomy; Group B (n = 33), septal myectomy and mitral valve (MV) repair; Group C (n = 22), myectomy and MV replacement; and Group D (n = 20), MV replacement alone. Median follow-up was 5.2 years (interquartile range 1.9-7.9). The mean resting LVOT gradient improved post-operatively from 71.9 ± 39.6 mmHg to 13.4 ± 18.5 mmHg (P < 0.05). Overall, 72.4% of patients improved by >1 New York Heart Association (NYHA) class; 58.9% of patients undergoing MV replacement alone did not improve their NYHA class. There were 5 perioperative deaths and 20 late deaths (>30 days). Survival rates at 1, 5 and 10 years respectively were 98.4, 96.9, 91.9% in Group A; 97.0, 92.4, 61.6% in Group B; 100.0, 100.0, 55.6% in Group C; and 94.7, 85.3, 85.3% in Group D (log-rank, P < 0.05). Long-term (>30 days) complications included atrial fibrillation (29.6%), transient ischaemic attack/stroke (2.4%) and heart failure hospitalisation (3.2%). There were 16 repeat surgical interventions at 3.0 years. CONCLUSION: Septal myectomy is a safe procedure resulting in symptomatic improvement in the majority of patients. The annual incidence of non-fatal disease-related complications after surgical treatment of LVOTO is relatively high. Patients who underwent MV replacements had poorer outcomes with less symptomatic benefit in spite of a similar reduction in LVOT gradients.

Risk scoring to guide antiplatelet therapy post-percutaneous coronary intervention for acute coronary syndrome results in improved clinical outcomes.

Aims: To use the Global Registry of Acute Coronary Events (GRACE) and Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) scores to risk stratify antiplatelet treatment post-acute coronary syndrome (ACS). Methods and results: This was a prospective registry of 3374 patients undergoing percutaneous coronary intervention for ACS between 2013 and 2015 at a UK cardiac centre. Patients with either low GRACE or high CRUSADE risk scores were stratified either to clopidogrel therapy or ticagrelor was used. The primary endpoint was major adverse cardiac events (MACE) defined as death, non-fatal myocardial infarction, stroke, or target vessel revascularization with bleeding rates as a secondary outcome, assessed at a median follow-up of 1.8 years (interquartile range 0.8-3.4 years). A total of 1723 (51.1%) patients were risk stratified to either clopidogrel (n = 520) or ticagrelor treatment (n = 1203), with the remaining 1651 not risk scored and treated with clopidogrel therapy. Patients in the risk score stratified group were older than the control group otherwise the groups were similar. Over the follow-up period, a significant reduction in MACE rates between the patients' risk score stratified and control (clopidogrel therapy) (13.7% vs. 19.7%, P < 0.0001) was seen [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.31-0.86]. This persisted after adjusting for baseline variables (HR 0.65, 95% CI 0.37-0.89) and propensity matching (HR = 0.63, 95% CI 0.27-0.93; P = 0.0015) No significant differences in the rate of major bleeding were seen between the groups (5.3% vs. 5.1%, P = 0.86). In the risk-stratified group, no difference in outcome (ischaemic/bleeding) was seen between clopidogrel and ticagrelor. Conclusion: Our registry data suggest that using appropriate risk scoring to guide antiplatelet therapy after ACS is safe and can result in improved clinical outcomes.

Predictors of atrial fibrillation in hypertrophic cardiomyopathy.

OBJECTIVES: Atrial fibrillation (AF) is associated with increased morbidity and mortality in patients with hypertrophic cardiomyopathy (HCM). The primary aim of this study (HCM Risk-AF) was to determine the predictors of AF in a large multicentre cohort of patients with HCM. Exploratory analyses were performed to investigate the association between AF and survival and the efficacy of antiarrhythmic therapy in maintaining sinus rhythm (SR). METHODS: A retrospective, longitudinal cohort of patients recruited between 1986 and 2008 in seven centres was used to develop multivariable Cox regression models fitted with preselected predictors. HCM was defined as unexplained hypertrophy (maximum left ventricular wall thickness of ≥15 mm or in accordance with published criteria for the diagnosis of familial disease). 28% of patients (n=1171) had coexistent hypertension. The primary end point was paroxysmal, permanent or persistent AF detected on ECG, Holter monitoring or implantable device interrogation. RESULTS: Of the 4248 patients with HCM without pre-existing AF, 740 (17.4%) reached the primary end point. Multivariable Cox regression revealed an association between AF and female sex, age, left atrial diameter, New York Heart Association (NYHA) class, hypertension and vascular disease. The proportion of patients with cardiovascular death at 10 years was 4.9% in the SR group and 10.9% in the AF group (difference in proportions=5.9%; 95% CI (4.1% to 7.8%)). The proportion of patients with non-cardiovascular death at 10 years was 3.2% in the SR group and 5.9% in the AF group (difference in proportions=2.8%; 95% CI (0.1% to 4.2%)). An intention-to-treat propensity score analysis demonstrated that ß-blockers, calcium channel antagonists and disopyramide initially maintained SR during follow-up, but their protective effect diminished with time. Amiodarone therapy did not prevent AF during follow-up. CONCLUSION: This study shows that patients with HCM who are at risk of AF development can be identified using readily available clinical parameters. The development of AF is associated with a poor prognosis but there was no evidence that antiarrhythmic therapy prevents AF in the long term.

Prevalence and outcomes of coronary artery perforation during percutaneous coronary intervention.

AIMS: We aimed to examine the prevalence, clinical outcomes and procedural characteristics of percutaneous coronary intervention (PCI) complicated by coronary artery perforation (CAP) in a contemporary patient population. METHODS AND RESULTS: Procedural records of 39,115 patients undergoing PCI between 2005 and 2016 were reviewed. CAP affected 149 cases (0.37%). The prevalence of CAP increased from 0.31% in 2005 to 0.45% in 2016 (p=0.03), reflecting an increase in more complex PCI (from 14% in 2005 to 21% in 2016; p<0.0001). CAP was associated with increased all-cause mortality (23.1% vs. 9.4% in those without perforation; p=0.0054) and was an independent predictor of mortality (HR 2.55; 95% CI: 1.34-4.78). In-patient mortality was 4% (6/149). In 43 of 149 (28.9%) cases, a significant pericardial effusion ensued and mortality rates were higher in this subgroup. Thirty-one patients had covered stents (CS) inserted and five did not survive to discharge. Of the 26 patients with a CS who survived to hospital discharge, six (23.1%) had definite stent thrombosis, and two (7.7%) had possible/probable stent thrombosis. CONCLUSIONS: CAP remains uncommon but the prevalence is increasing. CAP is associated with significant short- and long-term mortality, particularly when there is haemodynamic compromise necessitating pericardiocentesis. Covered stents are a valuable tool but they are associated with a high risk of stent thrombosis.

Stress, emotion and the heart: tako-tsubo cardiomyopathy.

Tako-tsubo cardiomyopathy is a cardiac syndrome precipitated by profound emotional stress and anxiety, particularly in middle-aged women. It presents as a mimic of acute myocardial infarction, but coronary angiography shows normal coronary arteries and a characteristic left ventriculogram resembling an "octopus pot". The condition seems to have a favourable prognosis. Initially described in Japan, and with many names in the literature, it is being increasingly recognised in the West owing to early coronary angiography and primary coronary intervention, accounting for up to 1 in 30 primary cases of angioplasty in some institutions. A typical case is described, and the clinical features, pathophysiology and management reviewed.

Drug-eluting stents appear superior to bare metal stents for vein-graft PCI in vessels up to a stent diameter of 4 mm.

BACKGROUND: Research trials have shown improved short-term outcome with drug-eluting stents (DES) over bare metal stents (BMS) in saphenous vein graft (SVG) percutaneous coronary intervention (PCI), primarily by reducing target vessel revascularization (TVR) for in-stent restenosis. We compared the outcomes in patients undergoing SVG stent implantation treated with DES or BMS. In exploratory analyses we investigated the influence of stent generation and diameter. METHODS: Data were obtained from a prospective database of 657 patients who underwent PCI for SVG lesions between 2003 and 2011. A total of 344 patients had PCI with BMS and 313 with DES. Propensity scores were developed based on 15 observed baseline covariates in a logistic regression model with stent type as the dependent variable. The nearest-neighbour-matching algorithm with Greedy 5-1 Digit Matching was used to produce two patient cohorts of 313 patients each. We assessed major adverse cardiac events (MACE) out to a median of 3.3 years (interquartile range: 2.1-4.1). MACE was defined as all-cause mortality, myocardial infarction (MI), TVR and stroke. RESULTS: There was a significant difference in MACE between the two groups in favour of DES (17.9% DES vs. 31.2% BMS group; p = 0.0017) over the 5-year follow-up period. MACE was driven by increased TVR in the BMS group. There was no difference in death, MI or stroke. Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.75 (95% confidence interval (CI) 0.52-0.94), with no difference in the hazard of all-cause mortality (hazard ratio: 1.08; 95% CI: 0.77-1.68). However, when looking at stent diameters greater than 4 mm, no difference was seen in MACE rates between BMS and DES. CONCLUSIONS: Overall in our cohort of patients who had PCI for SVG disease, DES use resulted in lower MACE rates compared with BMS over a 5-year follow-up period; however, for stent diameters over 4 mm no difference in MACE rates was seen.

Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy.

OBJECTIVE: A predictable relation between genotype and disease expression is needed in order to use genetic testing for clinical decision-making in hypertrophic cardiomyopathy (HCM). The primary aims of this study were to examine the phenotypes associated with sarcomere protein (SP) gene mutations and test the hypothesis that variation in non-sarcomere genes modifies the phenotype. METHODS: Unrelated and consecutive patients were clinically evaluated and prospectively followed in a specialist clinic. High-throughput sequencing was used to analyse 41 genes implicated in inherited cardiac conditions. Variants in SP and non-SP genes were tested for associations with phenotype and survival. RESULTS: 874 patients (49.6±15.4 years, 67.8% men) were studied; likely disease-causing SP gene variants were detected in 383 (43.8%). Patients with SP variants were characterised by younger age and higher prevalence of family history of HCM, family history of sudden cardiac death, asymmetric septal hypertrophy, greater maximum LV wall thickness (all p values<0.0005) and an increased incidence of cardiovascular death (p=0.012). Similar associations were observed for individual SP genes. Patients with ANK2 variants had greater maximum wall thickness (p=0.0005). Associations at a lower level of significance were demonstrated with variation in other non-SP genes. CONCLUSIONS: Patients with HCM caused by rare SP variants differ with respect to age at presentation, family history of the disease, morphology and survival from patients without SP variants. Novel associations for SP genes are reported and, for the first time, we demonstrate possible influence of variation in non-SP genes associated with other forms of cardiomyopathy and arrhythmia syndromes on the clinical phenotype of HCM.

Prediction of thrombo-embolic risk in patients with hypertrophic cardiomyopathy (HCM Risk-CVA).

AIMS: Atrial fibrillation (AF) and thrombo-embolism (TE) are associated with reduced survival in hypertrophic cardiomyopathy (HCM), but the absolute risk of TE in patients with and without AF is unclear. The primary aim of this study was to derive and validate a model for estimating the risk of TE in HCM. Exploratory analyses were performed to determine predictors of TE, the performance of the CHA2 DS2 -VASc score, and outcome with vitamin K antagonists (VKAs). METHODS AND RESULTS: A retrospective, longitudinal cohort of seven institutions was used to develop multivariable Cox regression models fitted with pre-selected predictors. Bootstrapping was used for validation. Of 4821 HCM patients recruited between 1986 and 2008, 172 (3.6%) reached the primary endpoint of cerebrovascular accident (CVA), transient ischaemic attack (TIA), or systemic peripheral embolus within 10 years. A total of 27.5% of patients had a CHA2 DS2 -VASc score of 0, of whom 9.8% developed TE during follow-up. Cox regression revealed an association between TE and age, AF, the interaction between age and AF, TE prior to first evaluation, NYHA class, left atrial (LA) diameter, vascular disease, and maximal LV wall thickness. There was a curvilinear relationship between LA size and TE risk. The model predicted TE with a C-index of 0.75 [95% confidence interval (CI) 0.70-0.80] and the D-statistic was 1.30 (95% CI 1.05-1.56). VKA treatment was associated with a 54.8% (95% CI 31-97%, P = 0.037) relative risk reduction in HCM patients with AF. CONCLUSIONS: The study shows that the risk of TE in HCM patients can be identified using a small number of simple clinical features. LA size, in particular, should be monitored closely, and the assessment and treatment of conventional vascular risk factors should be routine practice in older patients. Exploratory analyses show for the first time evidence for a reduction of TE with VKA treatment. The CHA2 DS2 -VASc score does not appear to correlate well with the clinical outcome in patients with HCM and should not be used to assess TE risk in this population.