Contemporary epidemiology of infective endocarditis in patients with congenital heart disease: A UK prospective study.

OBJECTIVES: Infective endocarditis is a life-threatening complication of congenital heart disease (CHD), but there are few studies concerning the contemporary risk profile, preceding invasive procedures and outcomes in this patient population. The aim of this study was to investigate the epidemiology of infective endocarditis (IE) in patients with CHD. METHODS: Cases of IE in children and adults with CHD were prospectively recorded as part of the UK National Institute for Cardiovascular Outcomes Research (NICOR) National Congenital Heart Disease Audit. Patients were entered into the database between April 2008 and March 2016. RESULTS: Eight hundred episodes of IE were recorded in 736 patients with CHD. Sixty-five patients (9%) were infants (aged <1 year), 235 (32%) were children (aged 1-15 years), and 436 (59%) were adults (aged >15 years). The most common diagnoses were Tetralogy of Fallot (n = 150, 22.8%), ventricular septal defect (n = 129, 19.6%) and bicuspid aortic valve (n = 70, 10.7%). Dental procedures preceded 67 of 635 episodes (11%) of IE, and non-dental invasive procedures preceded 177 of 644 episodes (27.4%). The most common causative organisms were streptococci, accounting for 40% of cases. Overall in-hospital mortality was 6.7%. On multivariable analysis, adverse factors associated with in-hospital mortality were staphylococcal infection and presence of an underlying atrioventricular septal defect. CONCLUSIONS: Infective endocarditis in patients with CHD is an ongoing clinical challenge. In contemporary practice in tertiary congenital centers, 1 of 15 patients do not survive to hospital discharge. Streptococci remain the most common causative organism, and antecedent dental or medical procedures were undertaken in a significant minority in the 3 months before diagnosis. The presence of an atrioventricular septal defect or staphylococcal infection is associated with significantly increased risk of early mortality.

Transcatheter aortic valve implantation: current status and future perspectives.

In the 16 years since the first pioneering procedure, transcatheter aortic valve implantation (TAVI) has come of age and become a routine strategy for aortic valve replacement, increasingly performed under conscious sedation via transfemoral access. Simplification of the procedure, accumulation of clinical experience, and improvements in valve design and delivery systems have led to a dramatic reduction in complication rates. These advances have allowed transition to lower risk populations, and outcome data from the PARTNER 2A and SURTAVI trials have established a clear evidence base for use in intermediate risk patients. Ongoing studies with an expanding portfolio of devices seem destined to expand indications for TAVI towards lower risk, younger and asymptomatic populations. In this article, we outline recent advances, new devices and current guidelines informing the use of TAVI, and describe remaining uncertainties that need to be addressed.

[Infective endocarditis in the elderly: The current view of the problem]. / Infektsionnyi éndokardit u pozhilykh: sovremennyi vzgliad na problemu.

The review gives the current views of the etiology and risk factors of infective endocarditis (IE) in the elderly. It reports the specific clinical picture of the disease at this age, including clinically apparent syndromes, comorbidity, and various clinical signs and peculiarities of IE. Particular emphasis is placed on the diagnosis of an endocardial infectious lesion, which is based on the use of the modified Duke criteria. The methods of IE diagnosis, particularly microbiological examination, imaging techniques, among which echocardiography in different modes plays a particular role, are listed. The treatment of the disease is based on the latest recommendations for antibiotic therapy with and without regard to a specific etiological factor. The issues of surgical intervention, as well as approaches to preventing IE in elderly people are discussed.

Right-sided valve disease.

In this review, we discuss right-sided heart valve disease, namely tricuspid regurgitation (TR), tricuspid stenosis, pulmonary regurgitation, pulmonary stenosis and right-sided endocarditis. These are frequently seen in conjunction with other diseases, making assessment of their significance more difficult, but it has become increasingly clear that moderate or severe right-sided heart valve disease, in particular TR, is associated with worse prognosis. There remain large gaps in our knowledge of medical and interventional treatment, but in this article we outline what is known about the causes, presentation and management of these commonly seen conditions.

Aortic valve disease.

Aortic valve disease is common and has significant impact on prognosis and quality of life. In this educational review, we cover the pathophysiology, presentation and assessment of aortic stenosis (AS) and aortic regurgitation (AR), including the role of imaging modalities beyond echocardiography. We review current treatment strategies and emphasise the use and indications for transcatheter aortic valve implantation (TAVI) in view of recent data highlighting its emergence as a novel treatment option for patients with AS, who are unsuitable for conventional aortic valve replacement (AVR). We also describe novel surgical approaches for AR and potential future strategies for percutaneous intervention.

Timing and mode of intervention for patients with left sided valvular heart disease: an individualized approach.

Left sided valvular heart disease poses major impact on life and lifestyle. Medical therapy merely palliates chronic severe valve disease and once symptoms or haemodynamic sequelae appear, life expectancy is markedly truncated. In this article, we review the mechanisms of valve pathology, latest evidence in the quest for pharmacological options, means by which to predict deterioration, and standard and novel treatment options.

Adjuncts to transcatheter aortic valve implantation.

INTRODUCTION: The appreciable rise in percutaneous valve procedures has been pursued by a wave of development in advanced technology to help guide straightforward, streamlined and safe intervention. This review article aims to highlight the adjunctive devices, tools and techniques currently used in transcatheter aortic valve implantation procedures to avoid potential pitfalls. Areas covered: The software and devices featured here are at the forefront of technological advances, most of which are not yet in widespread use. These products have been discussed in national and international structural intervention conferences and the authors felt it important to showcase particularly well designed adjuncts that improve procedural efficacy and safety. Whilst vascular pre-closure systems are used routinely and are an integral part of these complex cardiovascular procedures, these have been well summarised elsewhere and are beyond the scope of this article. Expert commentary: The rising volume of patients with aortic stenosis who are treatable with TAVI means that this exponential increase in procedures must be accompanied by a steady decline in procedural complications. This section provides an overview of our current perspective, and what we feel the direction of travel will be.

Contrasting inotropic effects of endogenous endothelin in the normal and failing human heart: studies with an intracoronary ET(A) receptor antagonist.

BACKGROUND: Endothelin-1 (ET-1) is a potent positive inotrope in vitro, but its physiological effects on intrinsic myocardial contractile function in humans in vivo are unknown. Plasma ET-1 levels are elevated in heart failure, and ET-1 may be involved in the pathophysiology of this condition. However, its effects on contractile function of the failing human heart are also unknown. METHODS AND RESULTS: A specific ET(A) receptor antagonist, BQ123, was infused (40 nmol/min, 16 minutes) into the left coronary artery in 8 patients with atypical chest pain (normal left ventricular ¿LV function and coronary arteries) and 8 patients with nonischemic dilated cardiomyopathy (DCM) who were undergoing diagnostic catheterization. In normal subjects, BQ123 rapidly induced a significant reduction in LV dP/dt(max) (-270+/-71 mm Hg/s after 16 minutes; P<0.05) and in LV dP/dt at a developed pressure of 40 mm Hg (LV dP/dt(40)) (-179+/-54 mm Hg/s; P<0.05). In DCM patients, however, BQ123 caused no reductions in LV dP/dt(max) (62+/-49 mm Hg/s after 16 minutes) or LV dP/dt(40) (83+/-51 mm Hg/s;P<0.05 compared with normal subjects). BQ123 had no effect on heart rate, LV relaxation, LV end-diastolic pressure, right atrial pressure, or pulmonary pressure in either patient group. CONCLUSIONS: Endogenous ET-1 has a tonic positive inotropic effect in normal subjects, independent of effects on the peripheral vasculature and unmasked by inhibition of ET(A) receptors. However, the effect of short-term ET(A) blockade in DCM patients was opposite to that in normal subjects, which suggests that ET-1 may cause negative inotropic effects in the failing heart.

The physiological role of endogenous endothelin in the regulation of human coronary vasomotor tone.

OBJECTIVES: The study was done to investigate the physiological role of endogenous endothelin-1 in the human coronary circulation by studying the effect of an intracoronary infusion of the specific endothelin receptor subtype A (ETA) receptor antagonist BQ123 on coronary vasomotor tone. BACKGROUND: Endothelin-1 contributes to the maintenance of peripheral vascular tone in humans. However, its physiological role in the human coronary vasculature is unknown. METHODS: We studied 12 patients (mean age 54.7 +/- 2.5 years, 3 men) undergoing cardiac catheterization for investigation of atypical chest pain, with angiographically normal coronary arteries. Coronary artery cross-sectional area was measured with digital quantitative coronary angiography, and coronary blood flow was assessed with an intracoronary Doppler flow wire. Flow-mediated (adenosine, 18 microg) and agonist-mediated (substance P, 20 pmol/min for 2 min) endothelial responses were measured prior to study. BQ123 (40 nmol/min for 15 min and monitored for a further 15 min) was infused into the left coronary artery. RESULTS: The BQ123 caused significant dilation of the proximal (artery cross-sectional area: 8.08 +/- 0.9 to 8.88 +/- 0.9 mm2; p < 0.05), mid (5.32 +/- 0.8 to 6.49 +/- 0.8 mm2; p < 0.001) and distal study vessel (2.11 +/- 0.2 to 2.50 +/- 0.2 mm2; p < 0.05). There was an increase in coronary blood flow (26.8 +/- 2.8 to 32.8 +/- 3.4 ml/min; p < 0.001) but no change in systemic hemodynamics. Baseline flow- or substance P-induced epicardial vasodilation did not correlate with the degree of vasodilation induced by BQ123. CONCLUSIONS: These data uncover a role of endogenous endothelin-1 in the maintenance of basal vasomotor tone in patients with angiographically normal coronary arteries.

Regulation of left ventricular relaxation in the isolated guinea-pig heart by endogenous endothelin.

OBJECTIVE: TO examine the effects of endogenous endothelin-1 on cardiac contraction in the isolated heart using endothelin receptor antagonists. METHODS: Isolated ejecting guinea-pig hearts were perfused with Krebs buffer (1 microM indomethacin) at 37 degrees C, constant loading and heart rate, and high-fidelity left ventricular pressure was monitored by an apical 2F Millar catheter. The effects of the following interventions on left ventricular performance and coronary flow were determined: (a) no treatment (i.e., time controls) (n = 8); (b) the specific ETA receptor antagonist, BQ123 (1 microM, n = 8); (c) the specific ETB receptor antagonist, IRL 1038 (0.1 microM, n = 4; 1 microM, n = 6); (d) exogenous endothelin-1 (0.01 nM, n = 6; 0.1 nM, n = 6); (e) the specific ETB receptor agonist, BQ3020 (5 nM, n = 8). RESULTS: All parameters were stable in control (untreated) hearts. BQ123 induced progressive acceleration of early left ventricular pressure decline and a fall in left ventricular end-diastolic pressure with no effect on peak left ventricular pressure, dP/dtmax, stroke volume or coronary flow. IRL 1038 had no effect on any of these parameters. In contrast, exogenous endothelin-1 exerted potent vasoconstrictor effects associated with a fall in peak left ventricular pressure, dP/dtmax and stroke volume. Similar changes were observed with BQ3020. Concentrations of endothelin-1 < 0.1 nM, which had no vasoconstrictor effect, produced no change in LV function. CONCLUSIONS: These data indicate that basal intracardiac release of endothelin-1 significantly delays LV relaxation in the isolated guinea-pig heart, but has no effect on coronary flow. The contrasting effects of endogenous endothelin-1 (elicited by BQ123) and exogenous endothelin-1 are likely to reflect differences in their site of action and in their effective concentrations at these sites.

What do we do when thrombolysis fails? A United Kingdom survey.

We conducted a postal survey amongst members of the British Cardiac Society to determine current strategies for the detection and management of failed thrombolysis for acute myocardial infarction. The response rate was 290/387 (75%). On-site cardiac catheterisation facilities are available to 162 (60%), 112 (41%) of which are prepared for urgent angiography +/- angioplasty. Streptokinase is the preferred routine thrombolytic agent (n = 242, 90%). After thrombolysis, 121 (45%) respondents rarely search for evidence of reperfusion; a further 55 (20%) confine their search to selected cases. Practice varies amongst those with an active management strategy following proven failed thrombolysis (n = 149, 55%): 50 (19%) perform urgent angiography +/- angioplasty, 49 (18%) administer another thrombolytic agent, 6 (2%) administer another dose of the same agent and 44 (16%) combine these approaches. Transfer to an interventional centre is considered by only 11/106 (10%) without on-site access to cardiac catheterisation. These data indicate considerable variation in the management of failed thrombolysis. Randomised, controlled trials are required to elucidate optimal treatment for this common and important clinical situation.

The influence of endothelium-derived nitric oxide on myocardial contractile function.

Nitric oxide released by cardiac endothelial cells modulates myocardial contractile function through elevation of intracellular 3',5'-cyclic guanosine monophosphate (cGMP). In the absence of agonist stimulation, nitric oxide typically enhances myocardial relaxation and reduces diastolic tone, without significantly altering the rate of force or pressure development. This pattern of effect is observed with nitric oxide or with cGMP analogues in isolated rat cardiac myocytes, isolated ferret papillary muscle preparations, and isolated ejecting guinea-pig hearts. In human subjects studied at cardiac catheterisation, low-dose bicoronary infusions of sodium nitroprusside or of substance P induce similar effects on left ventricular systolic and diastolic function. These changes may benefit from cardiac filling and coronary perfusion by increasing the diastolic interval, reducing extravascular compressive forces and increasing the driving pressure for filling, e.g., during exercise. Nitric oxide may also modulate inotropic and chronotropic responses to beta-adrenergic stimulation. Under pathological conditions, overproduction of nitric oxide by an inducible nitric oxide synthase may be detrimental for contractile function. Dysfunction of the constitutive nitric oxide pathway could also contribute to pathophysiology, e.g., in conditions characterised by diastolic dysfunction. The paracrine nitric oxide pathway is likely to be an important regulator of cardiac contractile function, acting in concert and interacting with other regulatory pathways.

The teratogenic metabolites of vitamin A in women following supplements and liver.

Ten healthy female volunteers were given 5 doses of retinol as the palmitate; 50 and 150 mg retinol as an oral supplement, 50 and 150 mg as fried calf liver (50 and 150 g) and 3, 9 or 30 mg by intra-muscular injection. Plasma concentrations of retinyl palmitate were higher after 50 mg retinol given as an oral supplement compared with 50 mg as liver; there was no significant difference between the 150 mg doses. Plasma concentrations of retinol showed only small increases. The peak plasma concentrations (Cmax) of all-transretinoic acid, the principal teratogenic metabolite of retinol, and the area under the concentration-time curve (AUC) were up to 20-times higher after supplements compared to the same dose as liver. Plasma concentrations of all-trans-4-oxo-retinoic acid, 13-cis-retinoic acid and 13-cis-4-oxo-retinoic acid showed smaller differences between supplements and liver. Intra-muscular administration of 30 mg retinol gave retinyl palmitate concentrations similar to those found after the oral doses but did not increase circulating concentrations of the acid metabolites. Based on the formation of all-trans-retinoic acid, liver and supplements are not of equivalent teratogenic potential. Advice to pregnant women on the consumption of liver based on the reported teratogenicity of vitamin A supplements should be reconsidered.

Percutaneous balloon mitral valvuloplasty.

Mitral stenosis is commonly encountered in the elderly and among immigrant communities. Percutaneous balloon mitral valvuloplasty provides effective treatment. The present article provides a brief overview of the principles of patient selection, technical details of the procedure itself and information concerning complications and follow-up.

The changing face of infective endocarditis.

Infective endocarditis (IE) is an evolving disease with a persistently high mortality and morbidity, even in the modern era of advanced diagnostic imaging, improved antimicrobial chemotherapy, and potentially curative surgery. Despite these improvements in health care, the incidence of the disease has remained unchanged over the past two decades and may even be increasing. Chronic rheumatic heart disease is now an uncommon antecedent, whereas degenerative valve disease of the elderly, mitral valve prolapse, intravenous drug misuse, preceding valve replacement, and vascular instrumentation have become increasingly common, coinciding with an increase in staphylococcal infections and those caused by fastidious organisms. The current understanding of this difficult condition is reviewed and recent developments in medical and surgical management are updated.