Trinity College of Florida.
Necrotic myocyte death occurs in ischemic heart disease purchase alli master card weight loss pills ephedrine uk, myocardial injury generic alli 60 mg mastercard weight loss nutrisystem, toxin exposure (e generic 60mg alli mastercard weight loss 4 supplement. The final result is a fibrotic scar, which may alter the structural and 34 functional properties of the myocardium. Information about regulated signaling in necrosis is currently limited to two pathways. The intrinsic pathway is activated by diverse biologic, chemical, and physical stimuli. These death signals trigger the release of apoptogens from the mitochondria into the cytosol, including cytochrome c, which triggers the formation of a second multiprotein complex, the apoptosome, in which procaspase-9 undergoes activation. Downstream caspases cleave several hundred cellular proteins to bring about the apoptotic death of the cell. Apoptosis, or programmed cell death, is an evolutionarily conserved process that allows multicellular organisms to selectively remove cells through a highly regulated program of cell suicide. In addition, connections between the pathways amplify signals, increasing the efficiency of killing. Apoptosis plays important roles in development and in postnatal life, when it is critical for tissue homeostasis and surveillance for damaged or transformed cells. In contrast with the cell swelling that characterizes necrosis, during apoptosis the cell shrinks and eventually breaks up into small, membrane-surrounded fragments. The latter often contain bits of condensed chromatin referred to as apoptotic bodies. Maintenance of plasma membrane integrity until late in the apoptotic process allows the dying cell to be engulfed by macrophages, which prevents the release of the reactive intracellular contents, thereby preventing an inflammatory reaction. Autophagy refers to the homeostatic cellular process of sequestering organelles, proteins, and lipids in a double-membrane vesicle inside the cell (autophagosome), where the contents are subsequently delivered to the lysosome for degradation. Unlike necrosis and apoptosis, autophagy is primarily a survival mechanism that regulates the quality and abundance of intracellular proteins and organelles. The three types of autophagy are macroautophagy, microautophagy, and chaperone-mediated autophagy. When autophagy involves the total destruction of the cell, it is referred to as autophagic cell death. Recent studies have demonstrated the existence of autophagic cell death in hypertrophied, failing, and hibernating 35 myocardium. Recent studies, however, have clearly demonstrated that autophagy has a variety of physiologic roles in the heart, and that impaired clearance of autophagosomes (impaired autophagic flux) may be deleterious, rather than the process of autophagy per 40 se. Although the distinction between necrosis and apoptosis is apparent in certain circumstances, it often is less clear in the failing heart. A, Although myocytes are the major components of heart on the basis of mass, they represent only a minority on the basis of number. Nonmyocyte cellular constituents of the myocardium include fibroblasts, smooth muscle cells, and endothelial cells. A, Intracellular signals generated by neurohormonal and/or mechanical stimulation of cardiac fibroblasts results in transcription and translation of nascent collagen proteins containing aminoterminal (N-terminal) and carboxyl terminal (C-terminal) propeptides that prevent collagen from assembling into mature fibrils. Once secreted into the interstitium, these propeptides are cleaved by N- and C-proteinases, yielding two procollagen fragments and a mature triple- stranded collagen molecule. Removal of the propeptide sequences allows the secreted collagen molecule to integrate into growing collagen fibrils, which can then further assemble into collagen fibers. After the collagen fibrils form in the extracellular space, their tensile strength is greatly strengthened by the formation of covalent cross-links between the lysine residues on the collagen molecules. B, The degradation of the collagen matrix within the myocardium entails a number of biochemical events involving several protease systems. Degradation of collagen fibrils occurs through catalytic cleavage of the three collagen alpha chains at a single locus by interstitial collagenase, yielding 36-kDa and 12-kDa collagen telopeptides that maintain their helical structure and thus are resistant to further proteolytic degradation. The large 36-kDa telopeptide spontaneously denatures into nonhelical gelatin derivatives, which in turn are completely degraded by interstitial gelatinases. In response to mechanical stress and neurohormonal activation, a subset of fibroblasts undergoes phenotypic conversion to myofibroblasts that are characterized by increased expression of α-smooth muscle actin and enhanced secretory activity. Recent studies have shown that myofibroblasts, which are responsible for the collagen secretion and contraction/realignment of the nascent collagen fibers, arises from tissue-resident fibroblasts that become 46 activated after tissue injury. Myofibroblasts migrate into the area surrounding tissue and play an important role in the final scar formation. Cardiac myofibroblasts also may regulate the phenotype of cardiac myocytes through multiple paracrine signaling pathways (Fig. Several lines of evidence 47 suggest that that cardiac fibroblasts and myocytes release proteins that regulate neighboring cells. The accumulation of collagen can occur on a “reactive” basis around intramural coronary arteries and arterioles (perivascular fibrosis) or in the interstitial space (interstitial fibrosis) and does not require myocyte cell death (eFig. Alternatively, collagen accumulation can occur as a result of microscopic scarring, which develops in response to cardiac myocyte cell necrosis. This scarring or “replacement fibrosis” is an adaptation to the loss of parenchyma and is therefore critical to preserve the structural integrity of the heart. The increased fibrous tissue would be expected to lead to increased myocardial stiffness, which presumably would result in decreased myocardial shortening for a given degree of afterload. In addition, myocardial fibrosis may provide the structural substrate for atrial and ventricular arrhythmias, thus potentially contributing to inhomogeneous activation, bundle branch block, and dyssynchrony, as well as sudden death (see Chapter 42). Although the full complement of molecules responsible for fibroblast activation is not known, many of the classic neurohormones (e. Histologic section of a human myocardial biopsy specimen showing interstitial (A) and perivascular (B) fibrosis using picrosirius red staining. The scaffolding around where the myocytes are positioned is evident and underscores the complexity of the fibrillar collagen matrix. Right, Schematic representation depicting the collagen matrix and the potential effects of mechanical load and proteolytic digestion of fibrillar collagen support. The geometric alignment of myocytes is disrupted, with loss of the rigid architecture of the matrix. Connective tissue skeleton in the normal left ventricle and in hypertensive left ventricular hypertrophy and chronic chagasic myocarditis. Additional content on this topic is presented in the online supplement for this chapter (Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases). Hypoxia results in the repression of miR-320 and miR-199, which promote and block apoptosis, respectively. Indeed, one of the first observations regarding the abnormal geometry of remodeled ventricle was the consistent finding that the remodeled heart was not only larger but also more spherical in shape. As shown in B, increase in short-axis dimension of ventricle as the heart becomes more spherical in shape leads to an increase in meridional wall stress of the ventricle, thereby creating a de novo mechanical burden for the heart. Left ventricular size and shape: determinants of mechanical signal transduction pathways. The former contributes directly to a state of energy starvation, whereas the latter contributes to further cardiac remodeling, including increased myocyte hypertrophy and further matrix remodeling.
Data are also lacking on whether branded nebivolol is more cardioprotective than generic carvedilol buy alli 60 mg otc weight loss pills from walmart, which is now included in $4/month formularies buy alli 60 mg visa weight loss pills on dr oz. Nebivolol can be dosed once daily with more consistent absorption independent of food intake purchase alli mastercard weight loss 6 weeks postpartum. Labetalol is effective treatment of hypertensive urgency but is too short-acting to be recommended for chronic hypertension management. By increasing blood flow in skeletal muscle, alpha blockers increase insulin sensitivity. Prazosin, doxazosin, terazosin, and intravenous phentolamine selectively block alpha1 adrenoceptors; phenoxybenzamine blocks both alpha and alpha receptors. When used in a combination regimen that includes a diuretic, however, they are effective add-on therapy for difficult hypertension and are particularly useful in older men with prostatism. These combined actions reduce adrenergic drive to the heart and peripheral circulation. Clinical Use and Side Effects The central sympatholytics are best reserved for short-term oral treatment of hypertensive urgency when beta blockers (i. To avoid rebound hypertension between doses, short-acting clonidine 80 must be given every 6 to 8 hours or, whenever possible, discontinued through gradual tapering. Rebound hypertension is less of a problem with guanfacine, a longer-acting oral central sympatholytic that is dosed at bedtime. Alpha- methyldopa is poorly tolerated and no longer a first-line therapy for hypertension in pregnancy. Clinical Use By causing selective and rapid arterial dilation, both drugs induce profound reflex sympathetic activation and tachycardia. Hydralazine is useful for the treatment of preeclampsia and as rescue therapy for very difficult hypertension. Initiation of chronic hemodialysis usually is a more effective means of controlling hypertension in this setting. Carotid Baroreflex Activation Therapy Electrical field stimulation of the carotid sinus, known as carotid baroreflex activation therapy, holds promise as a device-based intervention to supplement, but not replace, drug therapy for patients with 82 resistant hypertension. With the new data reviewed next, some but not all expert panels have begun to endorse more intensive therapy for hypertension for selected high-risk groups of patients (see Tables 47G. Because each of these subgroups comprised approximately 30% of the total cohort, the lack of a statistically significant intervention effect may be caused by subgroup sample size. In direct challenge to the 2014 guidance, the greatest risk reduction was in patients age 75 and older (Table 47. Intensive therapy did not increase rates of symptomatic orthostatic hypotension, injurious falls, or acute coronary syndrome, even in those 75 or older. This likely underpowered study yielded equivocal results except for a positive effect on hemorrhagic stroke (Table 47. With the patient unattended in the examination room for 5 minutes, an automatic monitor took three readings (one per minute), which were averaged. Because unknown numbers of patients in these trials were overtreated or undertreated, the optimal benefit of therapy was underestimated. Recent Observational Studies on Cardiac J-Curve Hypothesis Several new observational studies have rekindled the debate over the J-curve hypothesis (Table 47. Subsequent observational studies both support and contradict the J-curve hypothesis and raise concerns about reverse causality: comorbidity (e. Because only 28% of the cohort was being treated for hypertension, treatment-induced myocardial injury cannot be distinguished from other causes. Graphs plot the primary outcome (cardiovascular death, myocardial infarction, or stroke) against average systolic (A) or diastolic (B) blood pressure as splines. These analyses were adjusted using a Cox proportional hazards model that accounted for numerous risk factors and drug treatments. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study. Blood pressure and complications in individuals with type 2 diabetes and no previous cardiovascular disease: national population based cohort study. Parenthetically, the concept of the strictly diastolic cardiac J curve is partially flawed: while flow in the epicardial coronary arteries occurs mainly in diastole, blood flow within the myocardium (in 103 intramyocardial nutrient microvessels) occurs throughout the cardiac cycle. Systolic Hypertension in Elderly Patients Most hypertensive patients are older than 65 years, and most have isolated systolic hypertension (see Chapter 46). Moreover, ambulatory monitoring is key to detecting postprandial hypotension and orthostatic hypotension, which are common in hypertensive elderly patients (Fig. Useful strategies include frequent small low-carbohydrate meals, caffeine with meals, and liberalized salt intake. The evidence is insufficient to recommend the use of midodrine, an alpha-adrenergic agonist, for orthostatic hypotension, whereas recent evidence indicates that abdominal compression garments and droxidopa are the most effective and safest approaches to manage severe orthostatic 107-109 hypotension. Red arrows show repeated episodes of postprandial hypertension and one episode of orthostatic hypotension when the patient walked to the bathroom 90 minutes after going to sleep. Most patients will require combination therapy with two or three drugs, so it is important to titrate more slowly in elderly patients and to check frequently for orthostatic hypotension and adverse drug reactions, especially 74,75 thiazide-induced hyponatremia, which are more common. On average, elderly patients take more than six prescription drugs, heightening concern regarding polypharmacy, noncompliance, and potential drug interactions. Regimens with combination drugs and agents or formulations that permit less frequent dosing can simplify the treatment program and promote persistence. Beta blockers are the least effective; alpha- rather than beta-adrenergic receptors mediate the trophic effect of catecholamines on cardiac myocytes. Hypertension in Patients with Diabetes Mellitus and Normal Renal Function Patients with diabetes mellitus frequently have hypertension. Antihypertensive therapy should be instituted with one or more of the standard first-line drugs for hypertension. If additional drugs are needed to control hypertension, vasodilating beta blockers do not aggravate glucose tolerance in patients with type 2 diabetes. Reduction of Blood Pressure for Secondary Prevention of Stroke Stroke survivors are at high risk for recurrent stroke and thus further disability and death. Special Considerations in Management Special Populations Hypertension in Non-Hispanic Black Patients Hypertension proves particularly devastating in non-Hispanic black adults, who have a higher prevalence of hypertension than other groups and higher rates of hypertensive complications and death (see Chapter 46). Hypertension in Pregnancy Hypertensive disorders in pregnancy are a major cause of maternal-fetal morbidity and mortality, including a 25% incidence of preterm births (see Chapter 90). Four categories of hypertension in pregnancy are recognized: (1) preeclampsia, (2) chronic hypertension, (3) chronic hypertension with superimposed preeclampsia, and (4) gestational hypertension. Although the pathogenesis of gestational hypertension/preeclampsia remains enigmatic, risk factors include maternal age younger than 20 or older than 35, positive personal or family history of gestational hypertension, preexisting hypertension, obesity, diabetes, and antiphospholipid antibodies. Preeclampsia 121,122 is a risk factor for peripartum cardiomyopathy, conditions that may share common causative factors.
Trisomy 21 and Marfan and Ehlers- Danlos syndromes are associated with structural (especially valvular) heart disease order alli paypal weight loss pills recommended by dr oz. The phakomatoses may have neurologic involvement and seizures as part of the presentation order alli online weight loss now. In the absence of an intravenous line buy alli toronto weight loss pills costco, inhalational induction (avoiding contact of the mask on the eye) or intramuscular ketamine (with or without succinylcholine or rocuronium) may be considered, balanced against the risk of aspiration of gastric contents. Etomidate and propofol in combination with lidocaine (1 mg/kg iv) and/or fentanyl should be used to achieve a deep plane of anesthesia prior to laryngoscopy. If necessary, the surgeon can physically shield the eye to contain contents during induction. Maintenance may be inhalational or intravenous agents, planning for a smooth transition to spontaneous ventilation and extubation at the end of the case when appropriate. Lili X, Jianjun S, Haiyun Z: The application of dexmedetomidine in children undergoing vitreoretinal surgery. An ear speculum is inserted into the ear canal, cerumen is removed, and an incision is made in the tympanic membrane. Fluid is sometimes suctioned from the middle ear; then, a tympanostomy tube is inserted into the ear, straddling the tympanic membrane. Sometimes lidocaine and/or oxymetazoline drops are also inserted into the ear canal. The surgeon moves to the other side of the table, the microscope is repositioned, the head is turned, and the procedure is repeated on the other ear. Surgery should be delayed for patients with acute, febrile illnesses and in those with Sx referable to the lower airways (e. A mouth gag is inserted, and a small suction catheter is passed through the nose and brought out the mouth to elevate the soft palate and expose the nasopharynx. A curette, adenotome, microdebrider, or suction electrocautery is used to remove the adenoids; then, typically, the nasopharynx is packed. There are two major types of tonsillectomy: total tonsillectomy and subtotal (partial) tonsillectomy. The traditional total tonsillectomy is performed by grasping the tonsil with Allis forceps and pulling it medially. A vertical incision is made in the anterior tonsillar pillar with a sickle knife, scissors, or electrocautery instruments; then, the tonsil is dissected from the surrounding tissue and removed. After hemostasis has been obtained in the tonsillar fossae, the pack is removed from the nasopharynx, and hemostasis is achieved in the nasopharynx using suction electrocautery. Tonsils can also be completely removed using radiofrequency (Coblation), bipolar scissors, bipolar forceps, or laser. The same approach and setup is used for a subtotal tonsillectomy, which can be performed using radiofrequency or a microdebrider. The literature on incisional local anesthetic injection is mixed with some studies reporting benefit and some showing no benefit. Severe adenoidal hyperplasia may cause nasopharyngeal obstruction, obligate mouth breathing, failure to thrive 2° poor feeding, and disturbances of speech and sleep. Chronic nasal obstruction may result in narrowing of the upper airway and dental and facial changes (so-called adenoidal facies). Allford M, Guruswamy V: A national survey of the anesthetic management of tonsillectomy surgery in children. Francis A, Eltaki K, Bash T, et al: The safety of preoperative sedation in children with sleep-disordered breathing. Raeder J: Ambulatory anesthesia aspects for tonsillectomy and abrasion in children. The larynx is viewed with the patient breathing spontaneously so that vocal cord movement can be observed; then the anesthesia is deepened and the bronchoscope passed into the trachea. The trachea and bronchi are viewed, and when indicated, bronchoalveolar lavage or bronchial biopsy can be performed. Direct laryngoscopy is performed, and topical anesthetic is applied to the larynx and trachea. The anesthesia tubing is connected to the bronchoscope, and the patient is ventilated through the scope. During the time when the telescope is being changed, a leak will be present in the ventilation system. The esophagoscope is inserted through the mouth into the esophagus, and the entire length of the esophagus is viewed. Alternatively, a guide wire can be passed through the esophagoscope; then Savary/Gilliard dilators, in successively larger sizes, are passed over the wire. Another option is to remove the esophagoscope after the stenosis has been visualized; then, Maloney or Hurst dilators are passed blindly through the mouth and into the esophagus. Care must be taken to avoid accidental extubation of the patient while the dilators are being inserted and removed. For this proceure, the ideal plane at anesthesia simulates a physiologic sleep state. The patient should be breathing spontaneously and will be in a sitting (with support) or supine position. Topical anesthesia and vasoconstrictors are applied to the nose; then the scope is passed through the nose into the pharynx, and the larynx is viewed. Diagnostic direct laryngoscopy is performed with the child in a supine position, table turned 90°, with a small shoulder roll in place. The laryngoscope is introduced, and with a lifting motion, a thorough exam of the oropharynx, hypopharynx, and larynx is performed. If more than a brief exam is to take place, the vocal cords are anesthetized with topical lidocaine to help prevent laryngospasm. A telescope (often connected via camera to a video monitor) or rigid ventilating bronchoscope may be passed through the vocal cords to observe the trachea and major bronchi. The patient continues to breathe spontaneously or is paralyzed and jet-ventilated. When the laser is used, the patient’s eyes and face are covered with a damp cloth. A microscope with the laser attached is positioned so that the laser beam passes through the laryngoscope onto the vocal folds. Alternatively, the laser may be held by the surgeon and passed through an optical fiber. Young infants with severe laryngomalacia may undergo a supraglottoplasty for relief of airway obstruction. The laryngoscope is suspended, and the laser or microlaryngeal instruments are used to remove redundant aryepiglottic fold tissue. Children with subglottic or tracheal stenosis may undergo microdirect laryngoscopy with dilation, either by balloon or rigid dilator.
A chest radiograph is obtained by the surgeon at the first visit to assess for residual pleural fluid proven 60mg alli weight loss pills las vegas, pneumothorax discount alli 60 mg fast delivery weight loss pills reddit, lung aeration effective alli 60mg weight loss 2 weeks, and heart size. Recent studies estimate that 25% to 30% of patients with a bioprosthesis implanted for less than 10 years in the aortic 7 position have some degree of valve degeneration or dysfunction. In patients with mechanical valves, 2 routine annual echocardiography is not indicated in the absence of a change in clinical status. Evaluation and Treatment of Prosthetic Valve Dysfunction and Complications The suspicion of prosthetic valve dysfunction may be the appearance of a new murmur or symptom in a patient with a prosthetic valve or the incidental finding of abnormally high flow velocities and gradients detected during a routine echocardiography. Doppler-echocardiography is the method of choice to evaluate prosthetic valve function, identify and quantitate prosthetic valve stenosis or regurgitation, and 4,5 identify patient-prosthesis mismatch (Figs. Normal values for each valve type and size should be referenced, but simple thresholds of 3 and 4 meters per second (m/s) for Vmax and 20 and 35 mm Hg for mean Δp are a quick first step. Normal values for each valve type and size should be referenced, but the thresholds shown are a quick first step. In patients with intermediate measures of stenosis severity, the differential diagnosis includes significant stenosis, prosthesis-patient mismatch, and a high flow state. Transcatheter valve-in-valve implantation offers a valuable alternative to surgery for patients with failed bioprosthetic 26,31 valves who are at high or extreme surgical risk for reoperation (see Chapter 72). B, Cinefluoroscopy of bileaflet mechanical valve showing an immobile leaflet (orange arrow). C, Multidetector computed tomography with contrast injection showing area of hypoattenuation (orange arrow) indicating a thrombus on one of the leaflets of a balloon- expandable transcatheter valve. The leaflets are thickened (E, orange arrow), and the width of the transprosthetic jet is narrowed (F, white arrow) (see Video 71. Thomas Hospitals, London, and G, courtesy Arsène Basmadjian, Montreal Heart Institute. It can occur as a result of inadequate technique, suture dehiscence, compromised native tissue integrity (dense calcification, extensive myxomatous degeneration), infection, or chronic abrasion of the sewing ring against a calcified or rigid annulus. However, small paravalvular leaks may be associated with significant intravascular hemolysis and anemia as red blood cells are forced through a narrow orifice at high velocity. Despite a high clinical index of suspicion in this circumstance, a new, regurgitant murmur may not be audible. Larger paravalvular leaks may result in significant volume overload and heart failure, to an extent that reoperation might be indicated. Management can prove challenging, and a conservative approach with medical therapy is often chosen, in part related to the risks associated with reoperation in some patients. Thromboembolism and Bleeding Thromboemboli are a major source of morbidity in patients with prosthetic heart valves. Thromboembolic incidence rates are similar for non-anticoagulated patients with bioprostheses and appropriately anticoagulated patients with mechanical valves. The risk of bleeding, estimated at 1% per patient-year, increases with age and the intensity of anticoagulation. In patients with uncontrollable bleeding who require reversal of anticoagulation, administration of fresh-frozen plasma or prothrombin-complex concentrate is reasonable. Reoperation to implant a less thrombogenic valve is rarely undertaken for patients with recurrent thromboemboli despite aggressive antithrombotic therapy. Prosthetic Valve Thrombosis The incidence of mechanical valve thrombosis is estimated at 0. Thrombosis of a mechanical heart valve can have devastating consequences (see Figs. Bioprosthetic (surgical or transcatheter) valve thrombosis is less common, with a reported incidence of 0. Clinical suspicion of prosthetic valve thrombosis should be raised by symptoms of heart failure, thromboembolism, or low cardiac output, coupled with a decrease in the intensity of the valve closure sounds (mechanical valves), new and pathologic murmurs, or documentation of inadequate anticoagulation. Thrombosis is more common in the mitral and tricuspid positions than in the aortic position. Although differentiation from pannus formation can be difficult, the clinical context usually 4,5 allows accurate diagnosis. In patients with mechanical valves, confirmation of abnormal leaflet or disc excursion in the 5 presence of an occluding thrombus can also be obtained with cinefluoroscopy. Fibrinolytic therapy is generally 2 recommended for patients with right-sided prosthetic valve thrombosis. An encouraging report of the efficacy of low-dose, slow- infusion tissue plasminogen activator in pregnant women with prosthetic valve thrombosis should prompt 39 investigation of this approach in other patient subsets. Reoperative surgery or catheter closure of the defect is indicated when heart failure, a persistent transfusion requirement, or poor quality of life intervenes. Empiric medical measures include iron and folic acid replacement therapy and beta-adrenoreceptor blockers. Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the Veterans Affairs randomized trial. Utilization and mortality trends in transcatheter and surgical aortic valve replacement: the New York State experience—2011 to 2012. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Recommendations for the imaging assessment of prosthetic heart valves: a report from the European Association of Cardiovascular Imaging, endorsed by the Chinese Society of Echocardiography, the Inter-American Society of Echocardiography and the Brazilian Department of Cardiovascular Imaging. Long-term durability of bioprosthetic aortic valves: implications from 12,569 implants. Very long-term outcomes of the Carpentier-Edwards Perimount valve in aortic position. Meta-analysis of valve hemodynamics and left ventricular mass regression for stentless versus stented aortic valves. Long-term outcomes after autograft versus homograft aortic root replacement in adults with aortic valve disease: a randomised controlled trial. Incidence, predictors, and outcomes of aortic regurgitation after transcatheter aortic valve replacement: meta-analysis and systematic review of literature. Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. Aortic valve replacement: a prospective randomized evaluation of mechanical versus biological valves in patients ages 55 to 70 years. Long-term safety and effectiveness of mechanical versus biologic aortic valve prostheses in older patients: results from the Society of Thoracic Surgeons Adult Cardiac Surgery National Database. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years. Survival and outcomes following bioprosthetic vs mechanical mitral valve replacement in patients aged 50 to 69 years. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. Valve prosthesis-patient mismatch, 1978 to 2011: from original concept to compelling evidence.