Sex Differences in Right Ventricular Systolic Function and All-Cause Mortality in Tricuspid Regurgitation.

INTRODUCTION: Sex differences have been poorly studied in patients with right-sided heart valve disease. The principal aim of the current study was to explore the impact of sex differences on right ventricular (RV) hemodynamics and all-cause mortality in patients with moderate or severe tricuspid regurgitation (TR). METHODS: This is a retrospective study of 209 patients with significant TR. All patients were clinically profiled at baseline and underwent a transthoracic echocardiogram. The cohort was followed up for clinical events for a median duration of 80 months (mean ± SD 69.4 ± 33.4 months). RESULTS: There were 117 women with a mean (± SD) age of 72.6 ± 13 years and 92 men with a mean (± SD) age of 70.8 ± 15.8 years. There were no sex differences between the individual measures of RV systolic function (tricuspid annular plane systolic excursion [TAPSE], systolic pulmonary artery pressure, and RV S'), but overall RV systolic dysfunction (TAPSE <16 mm and/or RV S' <10 cm/s) and left ventricular ejection fraction <50% were more common in men. Mean (± SD) RV wall tension (RV WT) was 3,170 ± 1,220 mm Hg × mm in women and 3,817 ± 1,499 mm Hg × mm in men (p = 0.002). There was no difference in all-cause mortality between women and men (Log-Rank p = 0.528). Age and increased RV WT were independent predictors of all-cause mortality both in women (hazard ratio [HR] 2.61) and men (HR 3.01). CONCLUSIONS: In this cohort of patients with significant TR, women more frequently had preserved RV systolic function than men. There was no sex-difference in all-cause mortality. An increased RV WT and higher age were independent predictors of all-cause mortality in both women and men.

Clinical significance and prognostic value of ST segment depression on ECG during exercise treadmill test in asymptomatic patients with moderate or severe aortic stenosis.

Objectives. In patients with asymptomatic moderate or severe aortic stenosis (AS), exercise testing is used for evaluating the need for aortic valve intervention. Expert opinions about the clinical significance and prognostic value of ST segment depression on electrocardiography (ECG) during exercise testing in AS is conflicting and there are no large studies exploring this issue. We aimed to explore the association of ST segment depression >5 mm during exercise treadmill test (ETT) with all-cause mortality, aortic valve replacement (AVR) or cardiac-related hospitalization. Design. We performed a retrospective analysis of prospectively collected data of a total of 315 patients (mean age 65 ± 12 years, 67% men) with asymptomatic moderate (n = 209; 66%) or severe (n = 106; 34%) AS. All patients underwent clinical evaluation, echocardiography and ETT. Results. During a mean follow-up of 34.9 ± 34.6 months, 29 (9%) patients died and 235 (74%) underwent AVR. The prevalence of ST segment depression (>5 mm) was 13% (n = 41) in the total study population and was comparable in patients with revealed symptoms (17.6%, n = 16) versus without revealed symptoms (11.3%, n = 25; p = .132). ST segment depression on ETT was strongly associated with aortic valve area. In univariate Cox regression analysis, ST segment depression was not associated with cardiac related hospitalizations (HR 1.65; 95% CI 0.89-3.10, p = .113), all-cause mortality (HR 1.37; 95% CI 0.47-3.98, p = .564) or AVR (HR 1.30; 95% CI 0.89-1.91, p = .170). Conclusion. In patients with moderate or severe AS, ST segment depression during ETT is non-specific, carries no prognostic risk and should be used with caution in the clinical interpretation of exercise test.

Echocardiographic features of left ventricular recess, cleft, diverticulum, and aneurysm: A systematic review.

A pouch protruding into the wall of the left ventricle (LV) may be either a recess, cleft, diverticulum, or aneurysm. Being aware of these anomalies is essential to make accurate diagnosis and guide management decisions. Standard multimodality imaging of the heart enables detailed characterizations of LV fissures and outpouchings. They often present as an incidental finding on echocardiography, and the clinical significance can be difficult to address. We provide an overview of echocardiographic features of LV recess, cleft, diverticulum, pseudoaneurysms/aneurysms, and non-compaction based upon review of the literature as well as present some relevant clinical cases from our echocardiography labs.

First-phase ejection fraction by cardiovascular magnetic resonance predicts outcomes in aortic stenosis.

BACKGROUND: First-phase ejection fraction (EF1; the ejection fraction measured during active systole up to the time of maximal aortic flow) measured by transthoracic echocardiography (TTE) is a powerful predictor of outcomes in patients with aortic stenosis. We aimed to assess whether cardiovascular magnetic resonance (CMR) might provide more precise measurements of EF1 than TTE and to examine the correlation of CMR EF1 with measures of fibrosis. METHODS: In 141 patients with at least mild aortic stenosis, we measured CMR EF1 from a short-axis 3D stack and compared its variability with TTE EF1, and its associations with myocardial fibrosis and clinical outcome (aortic valve replacement (AVR) or death). RESULTS: Intra- and inter-observer variation of CMR EF1 (standard deviations of differences within and between observers of 2.3% and 2.5% units respectively) was approximately 50% that of TTE EF1. CMR EF1 was strongly predictive of AVR or death. On multivariable Cox proportional hazards analysis, the hazard ratio for CMR EF1 was 0.93 (95% confidence interval 0.89-0.97, p = 0.001) per % change in EF1 and, apart from aortic valve gradient, CMR EF1 was the only imaging or biochemical measure independently predictive of outcome. Indexed extracellular volume was associated with AVR or death, but not after adjusting for EF1. CONCLUSIONS: EF1 is a simple robust marker of early left ventricular impairment that can be precisely measured by CMR and predicts outcome in aortic stenosis. Its measurement by CMR is more reproducible than that by TTE and may facilitate left ventricular structure-function analysis.

Left atrial volume index predicts adverse events in asymptomatic moderate or severe aortic stenosis.

OBJECTIVE: In aortic stenosis (AS), chronic pressure overload on left ventricle (LV) leads to LV hypertrophy, impaired relaxation, increased chamber stiffness, fibrosis and left atrial (LA) dilatation. An enlarged LA may be a marker of longstanding diastolic dysfunction (DD) and more advanced disease in AS. We aimed to assess the impact of LA volume index (LAVI) on events in patients with moderate or severe AS. METHODS: A total of 324 patients (mean age 69 ± 13 years, 61% men) were included. LA volume was measured by biplane Simpson's method using apical four- and two-chamber views and indexed to body surface area. An increased LAVI was defined as > 34 ml/m2 . RESULTS: The mean EF was 64 ± 8%, LAVI 35 ± 14 ml/m2 and flow rate 244 ± 70 ml/s. The number of total events was 275 (85%): 243 (75%) aortic valve replacement and 32 (10%) deaths. Mean follow-up 23.7 ± 23.8 months (median 15.2 months). An increased LAVI (45% [n = 145]) was associated with adverse events (HR 1.86; 95% CI 1.24-2.82, p = 0.003) independent of age, smoking, diabetes, atrial fibrillation, LV ejection fraction, LV mass, aortic valve area, and low flow rate (<200 ml/s). In the same multivariate model, when increased LAVI was replaced by E/e' ratio ≥14 cm, no association was found between E/e' ratio ≥14 cm and adverse events (HR 1.18; 95% CI .78-1.78, p = 0.430). CONCLUSION: LAVI was an independent predictor of adverse events in patients with moderate or severe AS and preserved ejection fraction. Including LAVI in the risk assessment of AS patients may further improve risk stratification.

The electrocardiogram: Still a useful marker for LV fibrosis in aortic stenosis.

Left ventricular (LV) strain on the electrocardiogram (ECG) (down-sloping, convex ST-segment depression with asymmetric T-wave inversion in leads V5 and V6) reflects fibrosis as a result of subendocardial ischemia. It is associated with a significantly increased risk of cardiovascular events independent of the presence of LV hypertrophy on the echocardiogram or cardiac magnetic resonance (CMR) scan. Ongoing studies of early aortic valve replacement in asymptomatic patients with severe aortic stenosis are using ECG changes as a marker of possible fibrosis shown by midwall late gadolinium enhancement on CMR. However, until these studies report, it is still reasonable to respond to LV strain on the ECG by tightening control of systemic hypertension and consider intervention in cases where indications are otherwise in borderline.

First phase ejection fraction in aortic stenosis: A useful new measure of early left ventricular systolic dysfunction.

In aortic stenosis (AS), a left ventricular (LV) ejection fraction (EF) <50% or symptoms are class I indications for aortic valve intervention. However, an EF <50% may be too conservative since subendocardial fibrosis may already have developed. An earlier marker of LV systolic dysfunction is therefore needed and first phase EF (EF1) is a promising new candidate. It is the EF measured over early systole to the point of maximum transaortic blood flow. It may be low in the presence of preserved total LV EF since the heart may compensate by recruiting myosin motors in later systole. The EF1 is inversely related to the grade of AS and directly related to markers of subendocardial fibrosis like late gadolinium enhancement on cardiac magnetic resonance scanning. A reduced EF1 (<25%) predicts adverse clinical events better that total EF and global longitudinal strain. We suggest that it is worth exploring as an indication for surgery in patients with asymptomatic severe AS.

Quantifying infective endocarditis risk in patients with predisposing cardiac conditions.

Aims: There are scant comparative data quantifying the risk of infective endocarditis (IE) and associated mortality in individuals with predisposing cardiac conditions. Methods and results: English hospital admissions for conditions associated with increased IE risk were followed for 5 years to quantify subsequent IE admissions. The 5-year risk of IE or dying during an IE admission was calculated for each condition and compared with the entire English population as a control. Infective endocarditis incidence in the English population was 36.2/million/year. In comparison, patients with a previous history of IE had the highest risk of recurrence or dying during an IE admission [odds ratio (OR) 266 and 215, respectively]. These risks were also high in patients with prosthetic valves (OR 70 and 62) and previous valve repair (OR 77 and 60). Patients with congenital valve anomalies (currently considered 'moderate risk') had similar levels of risk (OR 66 and 57) and risks in other 'moderate-risk' conditions were not much lower. Congenital heart conditions (CHCs) repaired with prosthetic material (currently considered 'high risk' for 6 months following surgery) had lower risk than all 'moderate-risk' conditions-even in the first 6 months. Infective endocarditis risk was also significant in patients with cardiovascular implantable electronic devices. Conclusion: These data confirm the high IE risk of patients with a history of previous IE, valve replacement, or repair. However, IE risk in some 'moderate-risk' patients was similar to that of several 'high-risk' conditions and higher than repaired CHC. Guidelines for the risk stratification of conditions predisposing to IE may require re-evaluation.

Guidelines for the diagnosis, prevention and management of implantable cardiac electronic device infection. Report of a joint Working Party project on behalf of the British Society for Antimicrobial Chemotherapy (BSAC, host organization), British Heart Rhythm Society (BHRS), British Cardiovascular Society (BCS), British Heart Valve Society (BHVS) and British Society for Echocardiography (BSE).

Infections related to implantable cardiac electronic devices (ICEDs), including pacemakers, implantable cardiac defibrillators and cardiac resynchronization therapy devices, are increasing in incidence in the USA and are likely to increase in the UK, because more devices are being implanted. These devices have both intravascular and extravascular components and infection can involve the generator, device leads and native cardiac structures or various combinations. ICED infections can be life-threatening, particularly when associated with endocardial infection, and all-cause mortality of up to 35% has been reported. Like infective endocarditis, ICED infections can be difficult to diagnose and manage. This guideline aims to (i) improve the quality of care provided to patients with ICEDs, (ii) provide an educational resource for all relevant healthcare professionals, (iii) encourage a multidisciplinary approach to ICED infection management, (iv) promote a standardized approach to the diagnosis, management, surveillance and prevention of ICED infection through pragmatic evidence-rated recommendations, and (v) advise on future research projects/audit. The guideline is intended to assist in the clinical care of patients with suspected or confirmed ICED infection in the UK, to inform local infection prevention and treatment policies and guidelines and to be used in the development of educational and training material by the relevant professional societies. The questions covered by the guideline are presented at the beginning of each section.

Prognostic value of energy loss index in asymptomatic aortic stenosis.

BACKGROUND: Aortic valve area index adjusted for pressure recovery (energy loss index [ELI]) has been suggested as a more accurate measure of aortic stenosis (AS) severity, but its prognostic value has not been determined in a prospective study. METHODS AND RESULTS: The relation between baseline ELI and rate of aortic valve events and combined total mortality and hospitalization for heart failure resulting from the progression of AS was assessed by multivariate Cox regression and reclassification analysis in 1563 patients with initial asymptomatic AS in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. During 4.3 years follow-up, a total of 498 aortic valve events and 181 combined total mortalities and hospitalizations for heart failure caused by the progression of AS occurred. In Cox regression analyses, 1-cm(2)/m(2) lower baseline ELI predicted a 2-fold higher risk both for aortic valve events and for combined total mortality and hospitalization for heart failure independently of baseline peak aortic jet velocity or mean aortic gradient and independently of aortic root size (all P<0.05). In reclassification analysis, ELI improved the prediction of aortic valve events by 13% (95% confidence interval, 5-19), whereas the prediction of combined total mortality and hospitalization for heart failure resulting from the progression of AS did not improve significantly. CONCLUSIONS: In asymptomatic AS patients without known atherosclerotic disease or diabetes mellitus, ELI provides independent and additional prognostic information to that derived from conventional measures of AS severity, suggesting that ELI should be measured in such patients. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

Clopidogrel as prophylactic treatment for migraine: a pilot randomised, controlled study.

INTRODUCTION: Anecdotal reports suggest that clopidogrel may prevent migraine attacks. We undertook a pilot randomised trial. METHOD: We randomised consecutive migraineurs with four to 15 headache days per 28-day month to receive clopidogrel 75 mg or placebo daily for three months. Headache was primarily assessed with a headache diary. RESULTS: There were no statistically significant treatment effects. The number of headache days fell by 1.9 on clopidogrel and 1.6 on placebo (adjusted difference 0.02, CI -2.07 to 2.12). Headache severity rose by 0.14 points (out of 10) on clopidogrel, and fell by 0.63 on placebo; treatment effect 0.7 points (CI -0.11 to 1.57). The main treatment effect did not depend on the presence or absence of migraine with aura at baseline, a patent foramen ovale (PFO) or atrial septal aneurysm. DISCUSSION: The evidence is inconclusive, but a multicentre trial would be feasible recruiting from primary care.

Recent Insights Into Native Valve Infective Endocarditis: JACC Focus Seminar 4/4.

This focused review highlights the latest issues in native valve infective endocarditis. Native valve disease moderately increases the risk of developing infective endocarditis. In 2023, new diagnostic criteria were published by the Duke-International Society of Cardiovascular Infectious Diseases group. New pathogens were designated as typical, and findings on computed tomography imaging were included as diagnostic criteria. It is now recognized that a multidisciplinary approach to care is vital, and the role of an "endocarditis team" is highlighted. Recent studies have suggested that a transition from intravenous to oral antibiotics in selected patients may be reasonable, and the role of long-acting antibiotics is discussed. It is also now clear that an aggressive surgical approach can be life-saving in some patients. Finally, results of several recent studies have suggested there is an association between dental and other invasive procedures and an increased risk of developing infective endocarditis. Moreover, data indicate that antibiotic prophylaxis may be effective in some scenarios.

Antithrombotic therapy after heart valve surgery: contemporary practice in the UK.

OBJECTIVES: There is a lack of high-quality data informing the optimal antithrombotic drug strategy following bioprosthetic heart valve replacement or valve repair. Disparity in recommendations from international guidelines reflects this. This study aimed to document current patterns of antithrombotic prescribing after heart valve surgery in the UK. METHODS: All UK consultant cardiac surgeons were e-mailed a custom-designed survey. The use of oral anticoagulant (OAC) and/or antiplatelet drugs following bioprosthetic aortic valve replacement or mitral valve replacement, or mitral valve repair (MVrep), for patients in sinus rhythm, without additional indications for antithrombotic medication, was assessed. Additionally, we evaluated anticoagulant choice following MVrep in patients with atrial fibrillation. RESULTS: We identified 260 UK consultant cardiac surgeons from 36 units, of whom 103 (40%) responded, with 33 units (92%) having at least 1 respondent. The greatest consensus was for patients undergoing bioprosthetic aortic valve replacement, in which 76% of surgeons favour initial antiplatelet therapy and 53% prescribe lifelong treatment. Only 8% recommend initial OAC. After bioprosthetic mitral valve replacement, 48% of surgeons use an initial OAC strategy (versus 42% antiplatelet), with 66% subsequently prescribing lifelong antiplatelet therapy. After MVrep, recommendations were lifelong antiplatelet agent alone (34%) or following 3 months OAC (20%), no antithrombotic agent (20%), or 3 months OAC (16%). After MVrep for patients with established atrial fibrillation, surgeons recommend warfarin (38%), a direct oral anticoagulant (37%) or have no preference between the 2 (25%). CONCLUSIONS: There is considerable variation in the use of antithrombotic drugs after heart valve surgery in the UK and a lack of high-quality evidence to guide practice, underscoring the need for randomized studies.

An insight into transcatheter aortic valve implantation-a perspective from multidetector-computed tomography.

Transcatheter aortic valve implantation (TAVI) has now become an acceptable alternative to surgical aortic valve replacement for patients with severe aortic stenosis at high risk. The early enthusiasm for this technology has not diminished but rather has developed at an unprecedented rate over the last decade. Alongside the developments in implantation technique, transcatheter design, and postprocedural care, cardiac imaging modalities have also had to concurrently evolve to meet the perpetual demand for lower peri- and postprocedural complication rates. Although transthoracic and transesophageal echocardiography remain vital in patient's selection and periprocedural guidance, there is now emerging evidence that indicates that multidetector-computed tomography (MDCT) may also have an equally important role to play. The aim of the current review is to examine the modern role of MDCT in assessing patients with aortic stenosis being considered for TAVI.

Impact of gender, ethnicity and social deprivation on access to surgical or transcatheter aortic valve replacement in aortic stenosis: a retrospective database study in England.

OBJECTIVE: To assess gender, ethnicity, and deprivation-based differences in provision of aortic valve replacement (AVR) in England for adults with aortic stenosis (AS). METHODS: We retrospectively identified adults with AS from the English Hospital Episode Statistics (HES) between April 2016 and March 2019 and those who subsequently had an AVR. We separately used HES-linked Clinical Practice Research Datalink (CPRD) to identify people with AVR and evaluate the timeliness of their procedure (CPRD-AVR cohort). ORs for AVR in people with an AS diagnosis were estimated using multivariable logistic regression adjusted for age, region and comorbidity. AVR was considered timely if performed electively and without evidence of cardiac decompensation before AVR. RESULTS: 183 591 adults with AS were identified in HES; of these, 31 436 underwent AVR. The CPRD-AVR cohort comprised 10 069 adults. Women had lower odds of receiving AVR compared with men (OR 0.65; 95% CI 0.63 to 0.66); as did people of black (OR 0.70; 95% CI 0.60 to 0.82) or South Asian (OR 0.75; 95% CI 0.69 to 0.82) compared with people of white ethnicities. People in the most deprived areas were less likely to receive AVR than the least deprived areas (OR 0.8; 95% CI 0.75 to 0.86). Timely AVR occurred in 65% of those of white ethnicities compared with 55% of both those of black and South Asian ethnicities. 77% of the least deprived had a timely procedure compared with 58% of the most deprived; there was no gender difference. CONCLUSIONS: In this large, national dataset, female gender, black or South Asian ethnicities and high deprivation were associated with significantly reduced odds of receiving AVR in England. A lower proportion of people of minority ethnicities or high deprivation had a timely procedure. Public health initiatives may be required to increase clinician and public awareness of unconscious biases towards minority and vulnerable populations to ensure timely AVR for everyone.

Expert consensus recommendations for the provision of infective endocarditis services: updated guidance from the Joint British Societies.

Infective endocarditis (IE) remains a difficult condition to diagnose and treat and is an infection of high consequence for patients, causing long hospital stays, life-changing complications and high mortality. A new multidisciplinary, multiprofessional, British Society for Antimicrobial Chemotherapy (BSAC)-ledWorking Party was convened to undertake a focused systematical review of the literature and to update the previous BSAC guidelines relating delivery of services for patients with IE. A scoping exercise identified new questions concerning optimal delivery of care, and the systematic review identified 16 231 papers of which 20 met the inclusion criteria. Recommendations relating to endocarditis teams, infrastructure and support, endocarditis referral processes, patient follow-up and patient information, and governance are made as well as research recommendations. This is a report of a joint Working Party of the BSAC, British Cardiovascular Society, British Heart Valve Society, British Society of Echocardiography, Society of Cardiothoracic Surgeons of Great Britain and Ireland, British Congenital Cardiac Association and British Infection Association.

Outcome of patients with low-gradient "severe" aortic stenosis and preserved ejection fraction.

BACKGROUND: Retrospective studies have suggested that patients with a low transvalvular gradient in the presence of an aortic valve area < 1.0 cm² and normal ejection fraction may represent a subgroup with an advanced stage of aortic valve disease, reduced stroke volume, and poor prognosis requiring early surgery. We therefore evaluated the outcome of patients with low-gradient "severe" stenosis (defined as aortic valve area < 1.0 cm² and mean gradient ≤ 40 mm Hg) in the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. METHODS AND RESULTS: Outcome in patients with low-gradient "severe" aortic stenosis was compared with outcome in patients with moderate stenosis (aortic valve area 1.0 to 1.5 cm²; mean gradient 25 to 40 mm Hg). The primary end point of aortic valve events included death from cardiovascular causes, aortic valve replacement, and heart failure due to aortic stenosis. Secondary end points were major cardiovascular events and cardiovascular death. In 1525 asymptomatic patients (mean age, 67 ± 10 years; ejection fraction, ≥ 55%), baseline echocardiography revealed low-gradient severe stenosis in 435 patients (29%) and moderate stenosis in 184 (12%). Left ventricular mass was lower in patients with low-gradient severe stenosis than in those with moderate stenosis (182 ± 64 versus 212 ± 68 g; P < 0.01). During 46 months of follow-up, aortic valve events occurred in 48.5% versus 44.6%, respectively (P = 0.37; major cardiovascular events, 50.9% versus 48.5%, P = 0.58; cardiovascular death, 7.8% versus 4.9%, P = 0.19). Low-gradient severe stenosis patients with reduced stroke volume index (≤ 35 mL/m²; n = 223) had aortic valve events comparable to those in patients with normal stroke volume index (46.2% versus 50.9%; P = 0.53). CONCLUSIONS: Patients with low-gradient "severe" aortic stenosis and normal ejection fraction have an outcome similar to that in patients with moderate stenosis.

The case for a specialist multidisciplinary valve clinic.

Valve disease is common and is increasing in prevalence as the population ages. The delivery of appropriate management is not always straightforward, and better ways of organizing care are required. Here, the argument is made for a specialist multidisciplinary valve clinic, while a description is provided of the authors' model clinic, which incorporates a specialist cardiologist in addition to sonographers and a nurse who carry out the surveillance services. The clinic is based at a cardiothoracic center and one district hospital, but could be generalized. Previous audits have shown that this model can reduce the number of patients seen by a cardiologist, thus improving the safety and quality of treatment compared to conventional clinics.