Comparison of Mitral Valve Replacement and Repair for Degenerative Mitral Regurgitation: a Meta-analysis and Implications for Transcatheter Mitral Procedures.

PURPOSE OF REVIEW: Surgical mitral valve repair is considered superior to replacement to treat primary mitral regurgitation. However, the heterogeneity of cohorts and the lack of consideration of confounding in the published literature raise potential biases. The aim of this study was to pool all available matched data comparing outcomes of mitral valve repair and replacement in the setting of primary mitral regurgitation. RECENT FINDINGS: We searched Medline, Embase and the Cochrane Library Central Register of Controlled Trials to identify propensity-matched studies or reports with multivariable adjustment comparing repair and replacement in patients with primary mitral regurgitation. The primary outcome was all-cause mortality. DerSimonian and Laird random effects were used to perform the meta-analysis. Eight observational studies were selected including 4599 patients (3064 mitral repairs and 1535 replacements). Mean age ranged from 62 to 69 years, and the mean follow-up duration ranged between 3 and 9 years. Replacement was associated with an increased risk of long-term all-cause mortality compared to repair (HR of 1.68, 95% confidence interval 1.35-2.09, p < 0.001, τ2 = 0.03). Surgical era and atrial fibrillation impacted the risk of mortality but not mitral anatomy. Neither repair nor replacement impacted significantly on the risk of re-operation after mitral surgery (HR 1.18, 95% CI 0.85-1.63, p = 0.33, τ2 < 0.01). Mitral valve replacement is possibly associated with higher long-term mortality than mitral valve repair in primary mitral regurgitation but often used as a bailout option in more complex anatomy. Despite this observation, both techniques have similar risk of re-operation.

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.

Infective endocarditis in the military patient.

Infective endocarditis (IE) is a potentially fatal cardiac infection associated with an inhospital mortality rate of up to 22%. Fifty per cent of IE cases develop in patients with no known history of valve disease. It is therefore important to remain vigilant to the possibility of the diagnosis in patients with a febrile illness and unknown source. From a military perspective, our patients are unique due to the breadth of pathogens they are exposed to, and blood-culture-negative IE is a risk. In particular, there should be awareness of Coxiella burnetii as a possible causative pathogen. In this review we incorporate the latest consensus from systematic reviews and publications identified by a literature search through Medline. We describe the diagnosis and management of IE with particular reference to the military population.

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.

Infective Endocarditis in the Elderly: Diagnostic and Treatment Options.

Infective endocarditis (IE) is an uncommon, life-threatening systemic disorder with significant morbidity and persistently high mortality. The age of the peak incidence of IE has shifted from 45 years in the 1950s to 70 years at the present time, and elderly people have a five-fold higher risk of IE than the general adult population. Elderly IE patients demonstrate a higher prevalence of coagulase-negative staphylococci, enterococci and Streptococcus bovis, and lower rates of infection by viridans group streptococci. Methicillin resistance is more prevalent in elderly patients as a consequence of increased nosocomial acquisition. The elderly are a vulnerable group in whom diagnosis is often difficult on account of non-specific presenting features and where higher prevalence of comorbidities contributes to adverse outcomes. Treatment of older patients with IE presents specific challenges associated with prolonged antibiotic therapy, and access to surgery may be denied on account of advanced age and attendant comorbidities. This practical review covers all aspects of elderly IE, including clinical and microbiological diagnosis and appropriate diagnostic procedures, initial antibiotic selection, antibiotic prophylaxis, considerations about antibiotic therapy and surgery.

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.

Aortic stenosis - pathogenesis, prediction of progression, and percutaneous intervention.

Aortic stenosis is common and an important cause of morbidity and mortality. Prevalence will increase significantly in forthcoming decades as a function of the ageing population; treatment by means of surgery or percutaneous intervention is expensive. Epidemiological, mechanistic and interventional studies are therefore vital to determine optimal and innovative treatments and their funding. Recent studies suggest that aortic stenosis is not a passive degenerative disease, but an active process involving several pathways, including lipid infiltration, chronic inflammation, fibrosis formation, osteoblast activation, and active valve mineralisation. Despite similarities with atherosclerosis, randomised statin trials proved negative in aortic stenosis, underlining the need to explore alternative pathophysiological pathways. Left ventricular hypertrophy in response to pressure overload in aortic stenosis is initially adaptive but ultimately decompensates, leading to progressive left ventricular impairment, symptoms and adverse cardiovascular events. This transition is driven primarily by myocyte death and myocardial fibrosis. Cardiac magnetic resonance imaging can visualise and quantify myocardial fibrosis and may provide additional and independent prognostic information in aortic stenosis. Moreover, new markers of fibrosis utilising novel imaging techniques are rapidly emerging. Transcatheter aortic valve implantation is a disruptive technology that has transformed the management of aortic stenosis, and encouraged a wider multidisciplinary approach to the management of valvular heart disease. While originally applied in older, high-risk patients, recent trends for its use in intermediate risk patients have been supported by the findings of key clinical trials in 2016.

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.

Refractoriness to short day lengths augments tonic and gonadotrophin-releasing hormone-stimulated lutenising hormone secretion.

Siberian hamsters (Phodopus sungorus) undergo reproductive involution following exposure to short winter day lengths. Following approximately 20 weeks of exposure to short day (SD) lengths, hamsters become refractory to the inhibitory effects of SD, and reproductive competence is restored in anticipation of spring. The extent to which changes in gonadal steroid-dependent and -independent regulation of gonadotrophin secretion participate in this vernal reactivation of the gonads is not known. This experiment tested whether tonic and gonadotrophin-releasing hormone (GnRH)-stimulated regulation of lutenising hormone (LH) secretion differs between photoresponsive and photorefractory Siberian hamsters. Male hamsters born into long day (LD) lengths were castrated or subjected to a sham-castration surgery at 17 days of age, implanted s.c. with blank or testosterone-filled capsules, and housed in LD or SD thereafter. Baseline LH and LH responses to GnRH (200 ng/kg, s.c) were measured at 14 (photoresponsive) and 40 (photorefractory) weeks of age. Despite lower circulating testosterone concentrations in gonadally regressed SD hamsters on week 14, tonic LH concentrations were comparable among all groups of gonad-intact hamsters on weeks 14 and 40; however, week 14 SD hamsters exhibited significantly higher GnRH-stimulated LH responses. Tonic LH concentrations were indistinguishable among all groups of castrated hamsters bearing empty implants on week 14, but prolonged exposure to LD led to a decrease in resting LH, whereas prolonged exposure to SD resulted in an increase in LH. In castrated hamsters bearing testosterone implants, baseline LH concentrations were comparable in all groups, but GnRH treatment resulted in significantly higher LH concentrations in photorefractory (week 40, SD) hamsters relative to all other groups. The data suggest that the development of photorefractoriness in Siberian hamsters is characterised by enhanced gonadal hormone-independent stimulation of LH secretion, and diminished sensitivity to inhibitory negative-feedback effects of testosterone on LH secretion. Decreases in responsiveness of gonadotrophin secretion to gonadal hormone negative feedback may contribute to the process of photorefractoriness and assist in maintaining the growth of reproductive organs during the process of gonadal recrudescence.

Are the perioperative changes of serum magnesium in lung surgery arrhythmiogenic?

PURPOSE: To prospectively study the perioperative changes in serum magnesium (sMg) after major lung resections and their effect to the generation of cardiac dysrhythmias, and to present a brief review of the literature surrounding this phenomenon. PATIENTS AND METHODS: We studied 33 patients with non small cell lung cancer (NSCLC), scheduled for major pulmonary resection. Three patients were excluded from the study due to preoperative medication with beta-blocker and calcium (Ca) antagonists. Pneumonectomy was performed in 10 patients and lobectomy in 20. Heparinized arterial blood samples for the assessment of sMg, potassium (K) and Ca concentration were obtained before surgery, on arrival to the High Dependency Unit (HDU), and on the morning of the first and the second postoperative day. No patient had evidence of cardiac disease. RESULTS: Atrial fibrillation occurred in 3 (10%) patients. There was no statistically significant association between sMg and dysrhythmias. A statistically significant difference after adjusting for age was found between sMg concentration, just after the operation and the first post-operative day and the baseline measurement (before the operation). The type of surgical procedure was not found to be associated with the sMg concentration or the appearance of dysrhythmia. The serum K and Ca concentration for all samples was within normal range. CONCLUSION: Serum concentration of Mg decreases significantly within the first 24 hours of major lung resection. Although our study didn't demonstrate a relationship between decreases in sMg and the generation of arrhythmias, this link is well established in other fields and thus we support the prophylactic MgSO(4) administration in their prevention in such cases whilst we await further larger studies.

Guidelines on prophylaxis to prevent infective endocarditis.

Infective endocarditis is a devastating disease with high morbidity and mortality. The link to oral bacteria has been known for many decades and has caused ongoing concern for dentists, patients and cardiologists. Since 2008, the UK has been out of step with the rest of the world where antibiotic prophylaxis is recommended for high-risk patients undergoing invasive dental procedures. Recent evidence that identified an increase in endocarditis incidence prompted a guideline review by NICE and the European Society for Cardiology--which produces guidance for the whole of Europe. Despite reviewing the same evidence they reached completely opposing conclusions. The resulting conflict of opinions and guidance is confusing and poses difficulties for dentists, cardiologists and their patients. Recent changes in the law on consent, however, may provide a patient-centred and pragmatic solution to these problems. This Opinion piece examines the evidence and opposing guidance on antibiotic prophylaxis in the context of the recent changes in the law on consent and provides a framework for how patients at risk of endocarditis might be managed in practice.

A change in the NICE guidelines on antibiotic prophylaxis.

Since 2008, NICE clinical guidelines have stated: 'Antibiotic prophylaxis against infective endocarditis is not recommended for people undergoing dental procedures'. This put UK guidance at odds with guidance in the rest of the world, where antibiotic prophylaxis is recommended for patients at high-risk of infective endocarditis undergoing invasive dental procedures. Many dentists also felt this wording prohibited the use of antibiotic prophylaxis, regardless of the wishes of the patient or their personal risk of infective endocarditis and made it difficult for them to use their clinical judgment to deliver individualised care in the best interests of their patients. NICE have now changed this guidance to 'Antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures.' This article examines the implications of this small but important change.

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.

Short day lengths enhance skin immune responses in gonadectomised Siberian hamsters.

In Siberian hamsters and other photoperiodic rodents, exposure to short photoperiods simultaneously inhibits gonadal hormone secretion and enhances some measures of immune function. The present study tested whether gonadal hormones mediate the effects of short days on skin immune function (delayed-type hypersensitivity reactions) in male Siberian hamsters. The magnitude of delayed-type hypersensitivity reactions was greater in hamsters exposed to short days relative to those in long days. Comparable effects of photoperiod were obtained in castrated hamsters bearing empty or testosterone-filled implants. The data suggest that contemporary gonadal hormone secretion is neither necessary, nor sufficient to mediate the effects of short photoperiods on skin immune function.

Pineal-independent regulation of photo-nonresponsiveness in the Siberian hamster (Phodopus sungorus).

The pineal hormone melatonin influences circadian rhythms and also mediates reproductive responses to photoperiod. The authors tested whether pinealectomy influences circadian oscillators responsible for induction of nonresponsiveness to short day lengths by preventing normal short-day patterns of circadian entrainment. Adult male Siberian hamsters were pinealectomized or sham operated, maintained in either 18 h light per day (18L) or 15L for 10 weeks, and then tested for responsiveness to 10L. Because pinealectomized hamsters do not show gonadal regression in short day lengths, responsiveness was assessed by measuring phase angle of entrainment and the length of the nightly activity period following transfer to 10L. The incidence of nonresponsiveness was significantly higher in 18L hamsters than in 15L hamsters but was unaffected by pineal status. Fully 88% of 18L hamsters failed to entrain to 10L in the normal short-day manner; the duration of nightly activity remained compressed, and the phase angle of entrainment was large and negative relative to lights off. The 15L hamsters entrained normally to 10L. Exposure to constant light after 10L treatment was equally effective in inducing arrhythmicity in pinealectomized and intact hamsters. Changes in the period of morning and evening circadian oscillators subsequent to 18L treatment did not predict circadian responsiveness to short photoperiod. Long-day induction of photo-nonresponsiveness, which prevents winter responses to short day lengths, occurs independently of pineal melatonin feedback on the circadian system.