For example discount voveran online, exercise intolerance and dyspnea may be caused by obesity order generic voveran from india, pulmonary disease cheap voveran 50mg without a prescription, anemia, or deconditioning. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Changes in N-terminal pro-B-type natriuretic peptide levels and outcomes in heart failure with preserved ejection fraction: an analysis of the I-Preserve study. These demographic features may differ in specific populations and are associated with differences in race, ethnicity, and geographic region. This predilection may be a consequence of more severe comorbid disease, including hypertension, obesity, and diabetes. The presence of each of these 45 comorbidities predicts higher morbidity and mortality. Hypertension, obesity, diabetes, anemia, and renal dysfunction were present in many of these patients. Some evidence suggests that prolonged, sustained endurance training may slow or prevent some of the age-related changes. Women are shorter in stature than men, which may enhance the impact of reflected arterial waves on systolic pressure. Chronically increased systolic blood pressure is an important stimulus for cardiac structural remodeling and functional changes. This is caused by both the loss of atrial contraction and the resulting tachycardia. Increased adiposity not only imposes an adverse hemodynamic and metabolic load on the heart, but also is a source of a large number of biologically active peptide and nonpeptide mediators, many linked to chronic inflammation. In addition, direct effects of diabetes and hyperglycemia on myocardial structure and function have been described. In addition, the pulmonary vascular resistance may be increased by reactive pulmonary arterial vasoconstriction. In some patients, chronic pulmonary venous hypertension causes pulmonary vascular remodeling (congestive pulmonary vasculopathy), leading to irreversible pulmonary hypertension. The presence of increased pulmonary artery pressures has prognostic implications and is associated with higher morbidity and mortality rates. An important consideration in patients with previous malignancy treated with mediastinal irradiation is radiation-induced heart disease (see Chapter 81). The mechanisms responsible for these changes include worsening diastolic dysfunction, increased neurohormonal activation, and poorly controlled comorbid disease. Even after normal volume status is restored and neurohormonal activation suppressed, the inciting comorbidity may remain and can influence the subsequent clinical course. Transition from chronic compensated to acute decompensated heart failure: pathophysiological insights obtained from continuous monitoring of intracardiac pressures. Intracardiac pressures measured using an implantable hemodynamic monitor: relationship to mortality in patients with chronic heart failure. When mass or thickness is increased relative to (or out of proportion with) volume or dimension, the resultant changes are termed concentric remodeling. The methods necessary to quantify these abnormalities and the causative mechanisms are described earlier (see Pathophysiology). However, echocardiographic techniques can be used to assess these properties in a combinatorial fashion in order to characterize a diastolic function grade of 0 (normal), 1 (abnormal relaxation), 2 (pseudonormalized), 3a (reversible 25 restrictive), or 3b (irreversible restrictive) (Fig. This echocardiographic and Doppler echo– based grading scale is the most common clinical method of assessing severity of diastolic dysfunction. Normally, the early diastolic mitral flow velocity (E) and the mitral annular velocity (e′) are brisk and occur almost simultaneously. With mild diastolic dysfunction (impaired relaxation pattern—grade 1) the mitral E velocity is reduced and is less than the late diastolic mitral flow velocity (A). Echocardiographic evaluation of diastolic function can be used to guide clinical care. This results in a decrease in both the early transmitral flow velocity (E) and the early tissue velocity (e′) and an increase in the importance of late diastolic mitral flow velocity (A), the transmitral velocity resulting from atrial contraction, producing an E/A ratio less than 1. This filling pattern has been 64 termed an “impaired relaxation pattern” (abnormal relaxation) or grade 1 diastolic dysfunction. These changes result in a return of the E wave to the normal range (pseudonormal mitral inflow pattern). Thus the pseudonormal mitral inflow pattern is distinguished from normal by a reduced and delayed e′ and increase in the E/e′ ratio. With severe diastolic dysfunction, the late diastolic annular velocity (a′) also may be reduced, and pulmonary venous systolic forward flow velocity is reduced as well, to less than diastolic forward flow velocity. With grade 3 diastolic dysfunction, if a Valsalva maneuver causes a reduction of E wave velocity, the condition is designated reversible (grade 3a); if Valsalva does not change E, it is designated irreversible (3b). However, because direct measures of diastolic pressure are invasive and not suitable for repeated measures, noninvasive echocardiographic and echo-Doppler measurements have been developed and clinically applied. Prevalence and significance of alterations in cardiac structure and function in patients with heart failure and a preserved ejection fraction. Because e′ velocity from the lateral annulus usually is higher than the medial e′ velocity, the cutoff value should be adjusted to 12 if the lateral annular velocity is used. The clinical settings in which this application of E/e′ may be inaccurate are described in an online supplement for this chapter (Limitations 25 in Use of E/e′ Ratio). Echocardiographic findings related to diastolic function provide important prognostic information in a wide variety of patient populations. A normal filling pattern in community-dwelling patients indicates an 67 excellent prognosis. Similarly, an elevated E/e′ indicates a poor 64 prognosis in a wide variety of patients. Nevertheless, the practical clinical approach presented in this section will reduce symptoms, prevent acute decompensation, and improve exercise tolerance. Effects of digoxin on morbidity and mortality in diastolic heart failure: The Ancillary Digitalis Investigation Group Trial. Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction. These factors limited the power of the study, which did not show significant reduction in the primary endpoint. A cohort of 149 patients were assigned to receive therapy with sacubitril/valsartan (200 mg twice daily) and another 152 patients to receive valsartan (160 mg twice daily) for 36 weeks. Sacubitril/valsartan was well tolerated, with adverse effects similar to those for valsartan. The first aspect of management is reduction and prevention of pulmonary and peripheral venous congestion. These objectives can be accomplished with fluid and sodium restriction, judicious use of diuretics and nitrates, selective application of neurohormonal modulation, and appropriate remote monitoring–based tailored care. Strategies include controlling blood pressure at rest and modifying blood pressure response to exercise, controlling glucose, treating and preventing ischemia, maintaining adequate renal function, and treating obesity with medical and surgical weight loss management and exercise training. The third component of management is optimization of cardiac functional status—to prevent excessive tachycardia or bradycardia, to match heart rate to metabolic needs, to maintain or restore normal sinus rhythm, and to control ventricular response rate during atrial arrhythmias.
The vagal limb of the baroreceptor heart rate reflex also is responsive to arterial baroreceptor afferent inhibitory input order genuine voveran line. Healthy persons display low sympathetic discharge at rest and have a high heart rate variability buy discount voveran on-line. Increased sympathetic activation of the beta -adrenergic receptor results in increased heart rate and1 force of myocardial contraction order voveran with amex, with a resultant increase in cardiac output (see Chapter 22). In addition, the heightened activity of the adrenergic nervous system leads to stimulation of myocardial alpha -1 adrenergic receptors, which elicits a modest positive inotropic effect, as well as peripheral arterial vasoconstriction (Fig. Several clinical trials with vagal nerve stimulation did not meet their primary endpoint but have shown 4 encouraging trends in several secondary endpoints. However, the sustained expression of aldosterone may exert harmful effects by provoking hypertrophy and fibrosis within the vasculature and the myocardium, contributing to reduced vascular compliance and increased ventricular stiffness. The mechanism of action of aldosterone in the cardiovascular system appears to involve oxidative stress, with resultant inflammation in target tissue. Small-molecule therapies for cardiac hypertrophy: moving beneath the cell surface. Traditional theories have ascribed this increase to either “forward” failure, which attributes sodium retention to inadequate renal perfusion as a consequence of impaired cardiac output, or “backward” failure, which emphasizes the importance of increased venous pressure in favoring transudation of salt and water from the intravascular to the extracellular compartment. Aldosterone also may have direct + cardiac effects, in addition to increasing the reabsorption of sodium and the secretion of potassium (K ) +) and hydrogen (H ions in the collecting duct. Increased renal sympathetic nerve–mediated vasoconstriction leads to decreased renal blood flow, as well as increased renal tubular sodium and water reabsorption throughout the nephron. Increased renal venous pressure can also lead to renal interstitial hypertension, with the development of tubular injury and renal fibrosis. The V receptor,1a 2a 2 1a the most widespread subtype, is found primarily in vascular smooth muscle cells. The V receptors are found primarily in the2 epithelial cells in the renal collecting duct and the thick ascending limb. The V receptor mediates antidiuretic effects by stimulating adenyl cyclase to2 increase the rate of insertion of water channel−containing vesicles into the apical membrane. Because the vesicles contain preformed functional water channels, termed aquaporins, their localization in the apical membranes in response to V stimulation increases the water permeability of the apical membrane,2 leading to water retention. The “vaptans,” vasopressin receptor antagonists with V (relcovaptan) or V1a 2 (tolvaptan, lixivaptan) selectivity or nonselective V /V activity (conivaptan), have been shown to1a 2 reduce body weight and reduce hyponatremia in clinical trials (see Chapters 24 and 25). Once released, these cardiac peptides act on the kidney and peripheral circulation to unload the heart, through increased excretion of sodium and water, while inhibiting the release of renin and aldosterone (Fig. Potential reasons for this blunting include low renal perfusion pressure, relative deficiency or altered molecular forms of the natriuretic peptides, and decreased levels of natriuretic peptide receptors. A, The similar 17–amino acid disulfide ring in natriuretic peptides A, B, C, and D. The natriuretic peptides system in the pathophysiology of heart failure: from molecular basis to treatment. It has a wide range of tissue distribution, including vascular endothelium, smooth muscle cells, myocytes, fibroblasts, kidney tubule cells, and nerve cells. Overexpression of neprilysin ameliorated the development of Alzheimer disease, and disruption of the neprilysin gene induces cognitive dysfunction in a mouse model of Alzheimer disease. Neurohormonal Alterations in the Peripheral Vasculature In patients with heart failure, the complex interactions between the autonomic nervous system and local autoregulatory mechanisms tend to preserve circulation to the brain and heart while decreasing blood flow to the skin, skeletal muscles, splanchnic organs, and kidneys. This intense visceral vasoconstriction during exercise helps to divert the limited cardiac output to exercising muscle but contributes to hypoperfusion of the gut and kidneys. The increased sympathetic adrenergic stimulation of the peripheral arteries and the increased concentrations of circulating vasoconstrictors contribute to the arteriolar vasoconstriction and to the maintenance of arterial pressure. Additional content on this topic is presented in the online supplement for this chapter (Vasoconstricting Peptides in Heart Failure). Alterations in the kidney in heart failure: the cardiorenal axis in the regulation of sodium homeostasis. Kinins are vasodilators that are released from inactive protein precursors (kininogens) through the action of proteolytic enzymes termed kallikreins. Most cardiovascular actions are initiated by the B receptor, which is distributed1 2 2 widely in tissues, where it binds bradykinin and kallidin. Adrenomedullin is a 52–amino acid vasodilatory peptide that originally was discovered in human pheochromocytoma tissue. Subsequently, high levels of adrenomedullin immunoreactivity were detected in cardiac atrium and adrenal and pituitary glands, with lower levels detected in the ventricle, kidney, 15 and vasculature. Adrenomedullin receptors are present in multiple tissue beds, as well as both endothelial and vascular smooth muscle cells. In addition, apelin demonstrates potent inotropic activity without stimulating concomitant cardiac myocyte hypertrophy. In experimental animals, apelin concentrations are significantly lower in failing hearts and are increased after treatment with an angiotensin receptor blocking agent. Although adipose tissue was once considered as a simple storage depot for fat, adipose tissue is now known to synthesize and secrete a family of proteins collectively referred to as adipokines (see eFig. Leptin is a 16-kDa protein hormone that plays a key role in regulating energy intake and energy expenditure. The product of the ob gene, leptin is predominantly synthesized and secreted by adipocytes, although the heart is also a site of leptin synthesis. The initial role of leptin was thought to be decreasing appetite through hypothalamic stimulation and thus regulation of food intake. However, elevated circulating levels of leptin, which act via a family of receptor (ob. Lack of leptin and leptin resistance may lead to an accumulation of lipids in nonadipose peripheral tissues, resulting in a variety of “lipotoxic” effects, including cardiac myocyte apoptosis. Several studies 18 suggest that leptin directly induces hypertrophy in both human and rodent cardiac myocytes. Various circulating adipokines, the profile of which alters in obesity, may directly (solid lines) influence remodeling events known to occur in heart failure: hypertrophy, apoptosis, fibrosis, and metabolic alterations. Another potential mechanism whereby adipokines may influence cardiac structure and function is through indirect effects (broken lines) on parameters known to influence cardiac remodeling, such as hypertension, insulin resistance, and renal effects. Although adiponectin initially was thought to be exclusively produced by adipose tissue, recent studies have demonstrated adiponectin expression in the heart. The adult heart responds to tissue injury by synthesizing a series of proteins that promote homeostasis, either by activating mechanisms that facilitate tissue repair or, alternatively, by upregulating mechanisms 19 that confer cytoprotective responses within the heart. What has been less well understood, until recently, is how these myocardial innate immune responses are coordinated after tissue injury. Disease susceptibility genes may confer increased risk of disease progression after cardiac injury, whereas modifier genes can increase and/or decrease the impact of susceptibility genes.
There are no true erosions on radiography purchase voveran with a mastercard, 20 and the rheumatoid factor is usually negative purchase voveran toronto. A buy voveran 50 mg overnight delivery, Swan neck deformity in Jaccoud arthropathy, with ulnar deviation and metacarpophalangeal subluxation. The differential diagnosis of polyarticular arthritis in children and adolescents includes poststreptococcal reactive arthritis, other autoimmune diseases, septic arthritis, infective endocarditis, Lyme disease, lymphoma/leukemia, viral arthropathy and sickle cell disease. Poststreptococcal reactive arthritis is diagnosed in patients who have an arthritis that is not typical of rheumatic fever but who have evidence of recent streptococcal infection. The distinction between poststreptococcal reactive arthritis and rheumatic fever is unclear, and many would recommend that a diagnosis of poststreptococcal reactive arthritis not be made in populations in whom rheumatic fever is common. In some patients the carditis may be asymptomatic and is detected during clinical examination of a patient with arthritis or chorea. The incidence of carditis during the initial attack of rheumatic fever varies from 40% to 91% depending on the selection of patients and whether the diagnosis is made on clinical 23 assessment alone or combined with echocardiography. It is reported in 90% to 92% of children under age 3 years, in 50% of children age 3 to 6 years, in 32% of teenagers age 14 to 17 20 years, and only in 15% of adults with a first attack of rheumatic fever. In a 1951 review of 1000 patients, 65% were diagnosed as having carditis (see Classic References, Bland and Duckett Jones), and in the 1987 report of a Utah outbreak in the United States, 91% had carditis when clinical examination was combined with echocardiography (see Veasy). The symptoms and signs of carditis depend on whether there is involvement of the pericardium, myocardium, or heart valves. Myocardial damage may manifest with electrocardiographic changes, which include varying degrees of heart block. It occurs in 5% to 10% of the initial episodes and is more frequent during recurrences of rheumatic fever. Pericarditis is associated with anterior chest pain (see Chapter 83), and a pericardial friction rub may be detected on clinical examination. The pericardial effusion may sometimes be large, but cardiac tamponade is rare, and constrictive pericarditis does not occur. The most common valvular lesion is mitral regurgitation causing an apical pansystolic murmur. Stenotic lesions are uncommon in the early stages of the disease, but a transient apical mid-diastolic murmur (Carey-Coombs) may occur in association with the murmur of mitral regurgitation. Echocardiography is more sensitive and specific than cardiac auscultation for the detection of acute rheumatic carditis, such that it is recommended that all patients with suspected or definite rheumatic fever 24 should undergo echocardiography (see Classic References, Vasan). The advent of portable echocardiography has increased the availability of cardiac ultrasound to many people in developing countries, resulting in its increasing use in screening for subclinical rheumatic heart valve disease. World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease: an evidence-based guideline. Sydenham Chorea Chorea may be the only presenting manifestation of rheumatic fever. It is more common in females, and after puberty there is an even greater female predominance. The latent period between the episode of streptococcal pharyngitis and the development of chorea is considerably longer (6 to 8 weeks) than for arthritis and carditis. Chorea is characterized by the presence of involuntary, purposeless, jerky movements of the hands, arms, shoulders, feet, legs, face, and trunk associated with hypotonia and weakness. The purposeless movements interfere with voluntary activity and disappear during sleep. Initially, chorea may be confined to the face or one arm and sometimes may be unilateral (hemichorea). Patients also show motor impersistence by intermittently, involuntarily withdrawing the tongue when attempting to protrude it for 30 seconds (jack-in-the-box tongue). Chorea does not occur simultaneously with arthritis but may coexist with carditis. Some patients with chorea may have a cardiac murmur, whereas others may only later manifest involvement of the mitral valve. Sydenham chorea with motor tics may overlap with the involuntary jerks of Tourette syndrome. Subcutaneous Nodules The subcutaneous nodules of rheumatic fever resemble the nodules of rheumatoid arthritis and may be detected over the occiput, elbows, knees, ankles, and Achilles tendons. In rheumatic fever the nodules around the elbow tend to occur over the olecranon, whereas rheumatoid nodules tend to occur more distally along the extensor aspect of the upper forearm. They are usually smaller, more discrete, and less persistent than rheumatoid nodules. Nodules are usually seen in children with prolonged active carditis rather than in the early stages of rheumatic fever. Multiple crops of nodules may be related to the severity of the rheumatic carditis. It has a characteristic appearance and is therefore helpful in the diagnosis of rheumatic fever but is not pathognomonic of the disease. It extends centrifugally while the skin at the center returns to normal and has an irregular, serpiginous border. Erythema marginatum usually occurs in patients with carditis and may occur early or later in the course of the disease. When temperature is used as a minor diagnostic criterion, however, a cutoff value of higher than 37. The temperature usually decreases within 1 week and rarely lasts more than 4 weeks. Rheumatic pneumonia is uncommon and is difficult to distinguish from pulmonary edema and other causes of alveolitis. Diagnosis Although no specific clinical, laboratory, or other test exists to confirm conclusively a diagnosis of rheumatic fever, the diagnosis is usually made using the clinical criteria first formulated in 1944 by T. Joint manifestations are only considered in either the major or the minor category, but not in both categories in the same patient. First, subclinical valvulitis detected by echocardiography (as defined in Table 74. Second, there is recognition that the clinical utility of the Jones criteria is determined by the pretest probability and background disease prevalence in a population. To avoid overdiagnosis in low-incidence populations and underdiagnosis in high-risk populations, variability in applying diagnostic criteria in low-risk versus high-risk populations has been introduced in line with the 13,24 Australian guidelines. In moderate- to high-risk communities, monoarthritis and polyarthralgia have been added as major criteria to polyarthritis, and a temperature of 38°C and monoarthralgia are the revised minor criteria (see Table 74. The 2015 Jones criteria also recognize the clinical entity of “possible” rheumatic fever. It is appropriate for clinical judgment to be applied in parts of the world where rheumatic fever remains common and where it is not possible to fulfill the Jones criteria because of a lack of laboratory facilities to conduct the recommended investigations of a patient with suspected rheumatic fever, as listed in Table 23,24 74. When a diagnosis of possible rheumatic fever is made in a high-incidence setting, it is reasonable to consider offering 12 months of secondary prophylaxis, followed by reevaluation based on history, physical examination, and repeat echocardiogram.
The disarray generic voveran 50 mg with amex, however buy voveran 50mg amex, is not 52 Forensic Pathology nearly so marked or extensive buy voveran online now. Ventricular and supraventricular arrythmias are common in individuals with this condition. Echocardiographic evidence of hypertrophic cardiomyopathy is usually present in one or more closely related family members. In adolescents and young adults, hypertrophic cardiomyopathy may be the most common cause of sudden cardiac death. Valvular Disease Sudden death due to valvular disease usually involves either mitral valve prolapse (ﬂoppy mitral valve; myxomatous degeneration of the mitral valve) or aortic stenosis. The valve involved is usually the tricuspid valve and the individual an intravenous drug abuser. Until recently, it was estimated that 5–15% of the population had mitral valve prolapse. The arrhythmias are widely varied, with premature ventricular complexes being the most prevalent. The anatomical ﬁndings are voluminous, thickened, redundant Deaths Due to Natural Disease 53 valve leaﬂets showing myxomatous transformation of the valve substance, in the absence of any inﬂammatory change, and dilatation of the mitral annulus (Figure 3. The posterior leaﬂet of the mitral valve is allegedly involved more than the anterior, though this has not been the authors’ impression. Clinically, there is protrusion of the mitral leaﬂets into the left atrium during systole. Complications of mitral valve prolapse are sudden death due to ventricular ﬁbrillation, infective endocarditis, transient ischemic attacks and partial strokes secondary to clot or platelet aggregations orig- inating from the prolapsed valve, ruptured chordae tendinae, and progres- sion to mitral insufﬁciency. One would have to do a complete autopsy, including a thorough toxicological screen, to exclude other possible causes of death before making the diagnosis. In the cases the authors have seen, the myxomatous degeneration of the valves has been extremely marked and has involved both leaﬂets of the mitral valve. The victims have generally been female, with the youngest 12 years of age and the rest in their late teens, twenties, and early thirties. One 18-year-old girl, who had been on propranolol for her arrhythmias, had her medication stopped approximately a month before collapsing and dying in front of a number of witnesses. After mitral valve prolapse, the next most common cause of sudden death due to valvular disease is aortic stenosis (Figure 3. Mitral stenosis, once a common ﬁnding in the medical examiner’s ofﬁce, has almost disappeared due to the marked decline in rheumatic fever and the surgical treatment for mitral stenosis. Aortic stenosis may have four etiological causes: congenital malformation of the valve, rheumatic inﬂammation with fusion of the cusps, secondary calciﬁcation of congenital bicuspid valves, and primary degener- ative calciﬁcation of normal aortic valves. Congenital stenotic valves will develop secondary calciﬁcation as the individual gets older. This condition is rarely seen in the medical examiner’s ofﬁce because diagnosis has usually been made and treatment administered. Rheumatic aortic stenosis is becoming uncommon for the same reason that mitral stenosis is uncommon — the relative absence of rheumatic fever in the population. In rheumatic aortic stenosis, there is fusion of the cusps due to the inﬂammatory process. Calciﬁcation develops in patients as they grow older, generally over the age of 40. In both secondary calciﬁcation of the bicuspid valves and primary degen- erative calciﬁcation of the normal aortic valve, it is the calcium deposit that is the principal cause of the stenosis. With the bicuspid aortic valves, calci- ﬁcation begins in the 6th, 7th, and 8th decades of life, developing at the free 54 Forensic Pathology A [ B Figure 3. In primary degenerative calciﬁcation of normal aortic valves, the calciﬁcation progresses from the base toward the edges and usually involves individuals in the 8th and 9th decade of life. At the present time, the most common cause of aortic stenosis is calci- ﬁcation of bicuspid valves. It should be noted that bicuspid aortic valves, the precursor of calciﬁc aortic stenosis, are present in approximately 0. The aspect of aortic stenosis of most interest to the forensic pathologist is the propensity for sudden death. The mechanism of death is presumably acute myocardial insufﬁciency secondary to obstruction of the left ventricular outﬂow. The most disturbing case that the authors have seen with calciﬁc aortic stenosis was that of a commercial airplane pilot in his late forties who collapsed and died while jogging. Coronary Artery Anomalies Sudden death in adults and children may be associated with congenital anom- alies of the coronary arteries. Myocarditis The clinical manifestations of acute myocarditis may range from none to acute fulminating congestive heart failure to sudden death. Myocarditis can be caused by infectious agents (bacterial, rickettsial, viral, protozoal, fungal), connective tissue diseases (e. With infectious myocarditis, injury to the myocardium may be directly due to invasion by the organism or by toxin produced by the organism. Microscopically, there are patchy or diffuse areas of necrosis with interstitial inﬂammation. The inﬁltrate may vary from mostly neutrophils to lymphocytes, plasma cells, and esosinophils. Grossly, the appearance of the heart may be normal or pale and ﬂabby with dilated chambers. Ini- tially, there is inﬁltration by neutrophils and lymphocytes accompanied by necrosis of muscle ﬁbers. If ﬁbrosis develops, it may be either minor or extensive and may or may not be associated with subsequent arrhythmias. In a case seen by one of the authors, a 17-year-old boy at age 13 had a documented episode of viral myocarditis. Following that, he developed arrhythmias with occa- sional episodes of ventricular extrasystoles and tachycardia. For the 4 years following his episode of myocarditis, he had been followed by a cardiologist, who had documented his numerous episodes of arrhythmias. It was the expectation of the cardiologist that the heart would show extensive interstitial scarring. Multiple microscopic sec- tions of the heart taken from all areas, including the conduction system, were completely unremarkable. This shows that a viral inﬂammation of the heart can cause injury to the conduction system of the heart that cannot be detected or evaluated microscopically. This condition is probably the cause of some instances of sudden death in which the autopsy ﬁndings are completely negative.
When diffuse axonal injury has been documented following falls buy 50 mg voveran with amex, these have been falls from a considerable height order voveran without prescription. Death Due to Cerebral Concussion The authors have seen a number of deaths following blunt trauma to the head in which no order voveran 50mg, or at least insigniﬁcant, anatomical injury to the brain could be documented. The ﬁrst is illustrated by the case of an 8-year-old boy riding in the back seat of a motor vehicle that was involved in a head-on collision with another vehicle. The boy was propelled over the back seat, striking the top of his head against the wind- shield. At autopsy, there was no evidence of any injury to the scalp, skull, brain, or neck (anterior and posterior dissection). A second, similar case involved a 20-year-old man who fell 20 ft to the ground from a ladder. At autopsy, there was a small laceration of the scalp in the temporal region without fracture of the skull or gross evidence of injury to the brain. The second category of deaths involves individuals who, while acutely intoxicated with alcohol, are severely beaten about the head, usually with ﬁsts and feet (Figure 6. Analysis of vitreous humor indicates that, even if there had been prolonged survival, the blood alcohol level was never in the lethal range. The cause of death in this category of cases is posttraumatic apnea due to a combination of concussion and acute alcohol intoxication. With concussion alone, however, posttraumatic apnea is rare, brief, relatively mild and not life-threatening. Subarachnoid Hemorrhage Subarachnoid hemorrhage is the most common sequela of trauma to the head. In most cases, it is of a diffuse nature, overlying the cerebral hemispheres, with min- imal pooling on the ventral surface of the brain. Large collections of blood in the subarachnoid space of the base of the brain are more common in natural diseases than trauma, e. Hyperextension can cause bleeding because of lacerations of the basal or vertebral arteries. Blows to the face might produce lacerations of the internal carotid artery or a vessel of the circle of Willis. Blows to the neck can cause lacerations of a vertebral artery with dissection of blood superiorly into the subarachnoid space. In some instances, subarachnoid hemorrhage may be the only visible sign of trauma to the brain. Such was the case of an individual struck repeat- edly about the head with the barrel of a riﬂe, with resultant multiple lacer- ations of the scalp, but no fractures of the skull. The brain showed massive subarachnoid hemorrhage, but no contusions or lacerations. That subarach- noid hemorrhage in itself can cause death is illustrated by deaths following rupture of a berry aneurysm or laceration of a vertebral artery. While most subarachnoid hemorrhage is of venous origin, occasional cases are caused by lacerations of the vertebral artery or one of the basilar arteries of the brain. It is possible to have massive injury to the brain with minor focal sub- arachnoid hemorrhage, especially if death is rapid. This is seen most com- monly in cases with massive mutilating injuries of the head, such as when an individual jumps several stories to the ground. There are massive, gaping, compound fractures of the skull, with partial or even complete avulsion of the brain. In one case, an individual had his head caved in with a baseball bat in front of a number of witnesses. The brain showed virtually no subarachnoid hemorrhage and no contusions, though there were extensive lacerations. Absence of hemorrhage following lacerations to the brain has been reported as much as 1 h after injury, and is presumably due to prolonged spasm of vessels. This is due to subarachnoid hemorrhage causing scarring of the arachnoid villi, such that it impedes their ability to reabsorb cerebrospinal ﬂuid. Subarachnoid hemorrhage can be produced postmortem secondary to decomposition, with lysis of blood cells, loss of vascular integrity, and leakage of blood into the subarachnoid space. In addition, minimal subarachnoid hemorrhage may be produced during the process of removing the brain. In this case, in the process of removing the skull cap, cerebral veins and the arachnoid are torn, with subsequent diffusion of blood into the subarachnoid space in the posterior aspect (dependent portion) of the cerebral hemispheres and cerebellum. While this hemorrhage is usually very minor, if the brain is not removed from the cranial cavity immediately but rather left to sit for a while, a considerable quantity of subarachnoid hemorrhage may accumulate. Trauma to the Skull and Brain: Craniocerebral Injuries 175 Vertebral Artery Injury (Laceration) Blunt trauma to the neck can cause severe injury to the vertebral arteries. The upper third of the cervical region is the area where the vertebral artery is most susceptible to trauma. In the most common form, there is a traumatically induced dissection in the vessel wall, along a length of vertebral artery, with rupture into the subarachnoid space at the base of the brain (Figure 6. The second type of injury also involves dissection but, instead of rupture of the vessel wall, there is thrombosis of the lumen with infarction of brain tissue. The remaining two cases had rupture, but death was too rapid for subarachnoid hemorrhage. The most common causes of vertebral artery trauma are blows to the neck, motor vehicle accidents, falls, and cervical spine manipulation. Injury of the vertebral artery should be suspected when an individual collapses and dies almost immediately after receiving a blow to Figuren 6. In cases caused by rupture of the artery, an autopsy reveals sub- arachnoid hemorrhage primarily concentrated on the ventral surface of the brain and around the brain stem. In rupture of the artery due to blunt trauma, Opeskin and Burke noted bruising and abrasions below and behind the ear in 50% of 18 cases. Demonstration of the vertebral artery injury is easiest by injection of radio-opaque dye into the vertebral arteries with radiological demonstration of the injury. Only after such demonstration should there be dissection of the neck, because dissection is extremely difﬁcult and, if not done correctly, may produce artifactual defects in the vessels. Of 19 individuals with rupture and subarachnoid hemorrhage in the study of Opeskin and Burke, 14 died immediately and ﬁve in 10 h to 3 days. Of the four individuals who died secondary to vertebral artery thrombosis, symp- toms did not appear for 1 d to 4 weeks, with survival time of 3 days to 7 weeks. Traumatic Injury of the Carotid Artery This entity is probably more common than realized. In the neck, it may be found in association with hyperextension injury or spinal fracture. The injury was incurred in a low-speed motor vehicle collision and was due to deploy- ment of an airbag.
Mechanical (tilting disc) valves should not be crossed with a catheter because of the risk for catheter entrapment purchase 50mg voveran mastercard, occlusion of the 38 order cheapest voveran,39 valve buy cheap voveran 50 mg, or possible dislodgment and embolization of the disc (see Chapter 71). At that point, the needle and sheath are advanced into the left ventricle, the stylet and needle are removed, and the sheath is connected for pressure measurement. Left-Heart Catheterization As in most cases, catheters will not simply advance into the left ventricle; crossing the aortic valve requires careful technique (Fig. With deep inspiration or under pullback and clockwise rotation, the tip usually falls into the left ventricle. The catheter is positioned in front of the mitral valve, but not to interfere with its function or become entangled in the chordae. The Halo catheters represent an alternative to the pigtail catheters (see Classic References, Caracciolo). They possess a tip with a perpendicular helix, inwardly and upwardly directed, and do not have 6 to 12 side holes along the shaft as do pigtail catheters. Bottom row: Left, Use of a straight guidewire and pigtail catheter in combination. Increasing the length of the protruding guidewire straightens the curve of the catheter and causes the wire to point more toward the right coronary ostium; reducing the length of the protruding wire restores the pigtail contour and deflects the tip of the guidewire toward the left coronary artery. When the correct length of wire and the correct rotational orientation of the catheter have been determined, repeated advancement and withdrawal of the catheter and guidewire together allow retrograde passage across the valve. Right, In a small aortic root a right coronary Judkins catheter may have advantages. In patients with bicuspid valves an Amplatz left catheter is often used because it directs the wire more superiorly. In patients with bicuspid valves, a left Amplatz catheter might be useful for placement of a guidewire into the left ventricle, which directs more superiorly. A left Amplatz is also useful in patients with aortic stenosis, or a multipurpose catheter, depending on the angulation of the aortic valve from left ventricle into ascending aorta (more horizontal or more vertical). On occasion, straight rather than J-tipped guidewires have been used, which facilitates probing of the stenotic aortic valve, but also has greater potential for dislodging material from the aortic valve or aorta. For pressure measurements and contrast injections in the left ventricle, a pigtail catheter should be used because the risk of damaging the wall is reduced and the risk of entrapment of the mitral valve apparatus is low. The gradient across the aortic valve should be measured by simultaneous recording of pressure in the ascending aorta and left ventricle; pullback gradients do not suffice. Pigtail catheters with a dual lumen (distal and proximal) allow for this measurement, but the concordance of pressure should be verified in the aortic root before and after measurement. An alternative is the use of a multipurpose catheter through which a pressure wire is advanced into the left ventricle while the catheter remains in the aorta. Left Ventriculography Once considered an integral part of every cardiac catheterization, a left ventriculogram is infrequently performed in the current era given the advances in availability and quality of echocardiography (see Chapter 14) and concerns for complications. Ideally, left ventriculography should be performed in two planes, and biplane x-ray systems are therefore of great value. The pulmonary artery would also be the site of injection for the evaluation of pulmonic regurgitation. As a general rule, contrast is injected just distal to the valve that is to be evaluated. After the catheter is appropriately placed, it is connected to the power injector with high-pressure tubing, tight and air free. The power injector is then programmed to deliver 20 to 50 mL of contrast at 10 to 15 mL/sec. For smoother delivery and so that maximum pressure (900 to 1200 psi) is not reached instantly but more slowly, a 0. To facilitate lower contrast volumes, power injections can also be operator controlled and stopped once the ventricle is satisfactorily opacified. The main complications of left ventriculography are cardiac arrhythmias (both supraventricular and ventricular). Intramyocardial contrast staining during power injection can occur but is not clinically relevant if transient. This is a concern when end- hole catheters such as the multipurpose catheter are used for power injections into the left ventricle, which should never be done. Transient hypotension of 15 to 30 seconds was relatively common with the use of ionic high-osmolar contrast media but is not typically seen in the current era. The wall motion pattern ranges from normokinesis to hypokinesis, akinesis, and dyskinesis. A side-hole (pigtail) catheter should be used to reduce the risk of aortic injury. In the case of concerns for aortic dissection, one must ascertain that the catheter is not entrapped in the false lumen. For dissection, the optimal position is just above the suspected proximal tear, for the aortic valve just above the leaflets. Right-Heart Catheterization The right-heart catheterization is one of the central elements in the hemodynamic evaluation in the catheterization laboratory. Percutaneous venous access is accomplished via the internal jugular vein or femoral vein, or less frequently the subclavian or antecubital vein, as previously outlined. The Swan-Ganz catheter is the catheter of choice for the internal jugular approach (eFig. End-hole catheters, or “balloon wedge catheters,” are equally good for this purpose, with similar rigidity, less catheter whip artifact, and thus higher fidelity (eFig. The proximal ports, left to right, are the proximal injection hub, thermistor connector, distal lumen hub, and balloon inflation valve with syringe. C, Example of a diagnostic pressure catheter (Mikro-Cath, Millar, Houston, Texas). Although one can orientate oneself with pressure tracings only, fluoroscopy is advisable, especially if there are any preknown structural and functional difficulties (e. On occasion, the catheter can be advanced directly through the right atrium and across the tricuspid valve. Once in the outflow tract, the tip of the balloon usually allows flotation into the pulmonary artery and wedge positions. Deep inspiration or cough can facilitate this maneuver and assist in crossing the pulmonic valve. In patients with high pulmonary artery pressure, a guidewire can be used to stiffen the catheter and allow advancement into the wedge position. However, the operator must use caution to prevent perforation of the pulmonary artery. The catheter is then pulled back into the right atrium and with another clockwise rotation turned anteromedially, which allows the catheter to face and cross the tricuspid valve. Clockwise rotation causes the tip of the catheter to sweep anteromedially and cross the tricuspid valve. The reverse-loop technique (right) gives the tip of the catheter an upward direction, aimed toward the outflow tract. With the loop in place, the catheter is advanced further, and with the tip facing inferiorly and medially, the tricuspid valve is passed and the pulmonary artery and wedge positions are reached.
In all series there are high-risk patient populations buy 50mg voveran with visa, such as those with clinically significant 9-11 pulmonary hypertension or dilated aortas purchase voveran 50mg mastercard, who are underrepresented order discount voveran online. A British working group created a risk stratification tool using a World Health Organization classification that incorporates general and 12,13 lesion-specific diagnoses. All of these risk prediction tools should be used as a guide, along with known lesion-specific risks, other clinical information, and, of course, clinical judgment. There is a growing population of women conceiving with fertility therapy, including women with heart 14 disease. When fertility therapy is being considered in the cardiac patient, in addition to the cardiac- related risks described earlier, it is important to consider the risks associated with the underlying cause of infertility (i. Contraindications to Pregnancy In some situations, the maternal risk from pregnancy is prohibitively high, and women should be counseled to avoid pregnancy and sometimes even to consider termination of pregnancy if it occurs (Table 90. No data exist regarding the precise level of pulmonary hypertension that poses a major threat to the mother, but systolic pulmonary artery pressures higher than 60% to 70% of the systemic pressure are likely to be associated with maternal compromise; in these circumstances, pregnancy is best avoided. Women who have a left ventricular ejection fraction of less than 30% from any cause are not likely to withstand the volume load that pregnancy imposes and should be advised not to become pregnant. Patients with Marfan syndrome and a dilated aortic root more than 45 mm in diameter are vulnerable to progressive aortic dilation, dissection, and rupture during pregnancy. A number of other high-risk cardiac conditions, such as complex congenital heart disease, mechanical valves, and severe 14a,14b asymptomatic aortic stenosis, require careful preconception risk stratification. Because of the altered hemodynamics during pregnancy, the physical examination findings in a healthy pregnant woman reflect such changes and may mimic those in cardiac disease. By the middle of the second trimester, the jugular venous pressure may be slightly elevated, with brisk descents, because of the volume overload and reduced peripheral resistance. The second sound also may appear accentuated, and these combined auscultatory features may suggest an atrial septal defect or pulmonary hypertension. An ejection systolic murmur is commonly heard at the left sternal edge, never more than grade 3/6 in intensity, which relates to increased flow through the left or right ventricular outflow tract. Continuous murmurs also may be heard, as either a cervical venous hum or a mammary souffle, and are caused by the hyperdynamic circulation. The mammary souffle (continuous or systolic) is due to increased flow in the mammary arteries and is heard over the breast late in pregnancy or during lactation. Laboratory Evaluation Despite the hemodynamic volume load of pregnancy, most healthy pregnant women have low levels of B- type natriuretic peptide throughout pregnancy and after delivery. By comparison, women with heart disease have higher B-type natriuretic peptide levels throughout pregnancy compared with nonpregnant women, and normal B-type natriuretic peptide levels have a good negative predictive value for predicting 15 adverse cardiac events. Imaging Chest Radiography A chest radiograph is not obtained routinely in any pregnant patient because of concern about radiation exposure to the fetus, but it should not be withheld when the history and clinical findings raise concerns about maternal cardiac status. The chest radiograph in a normal healthy patient may show slight prominence of the pulmonary artery, and as pregnancy advances, elevation of the diaphragm may suggest an increase in the cardiothoracic ratio. Echocardiography Transthoracic echocardiography is the cornerstone of cardiac evaluation in pregnancy. In a normal pregnancy, the left ventricular end-diastolic measurement is slightly increased, and there may be similar increases in right ventricular size and the volumes of both atria. There can also be a small increase in the left ventricular wall thickness during pregnancy. Measurement of ejection fraction is determined by changes in preload and afterload, and with the patient in the supine position, preload may be reduced because the fetus may compress the inferior vena cava. The increased cardiac output leads to increases in the velocities across the left and right ventricular outflow tracts. Careful comparison of the two- dimensional anatomic appearances will help differentiate this from a true valvar abnormality. The valve area calculation may be more helpful than a simple measurement of valve gradient; the latter may appear to be increased as pregnancy advances because the circulation becomes more hyperkinetic and cardiac output increases. Transesophageal echocardiography is seldom performed during pregnancy; however, when necessary, it can be performed safely, although careful monitoring of maternal oxygen saturation is necessary if midazolam is used for sedation. General Management Principles During Pregnancy During pregnancy, a multidisciplinary team approach is recommended, with close collaboration with the obstetrician, so that the mode, timing, and location of delivery can be planned. The frequency of clinical visits is based on the underlying cardiac condition, with high-risk women being followed more often. Serial echocardiograms during pregnancy are useful in women with mechanical valves who are vulnerable to development of thrombosis during pregnancy, women with ventricular dysfunction, and women at risk for aortic root dilation. Medical Therapy Medical therapy should not be withheld when women develop cardiovascular complications during pregnancy; however, when administration of cardiovascular drugs is being contemplated, the potential fetal adverse effects of the drugs require consideration. For many cardiovascular medications, there are limited data on medication safety during pregnancy, and clinical decisions must be made based on the benefit for the patient versus the potential fetal and neonatal risks. A medication should be given only if the benefits are felt to outweigh the potential risk to the fetus. Principles to be considered include the use of drugs with the longest safety record, the use of the lowest dose and shortest duration necessary, and avoidance of a multidrug regimen, if possible. Balloon valvuloplasty is performed during pregnancy in women with severe mitral, pulmonary, or aortic stenosis who have symptoms refractory to medical therapy, provided the valve anatomy is favorable. Most valvuloplasties are successful in improving valve gradients, but worsening regurgitation, arrhythmias, tamponade, maternal death, precipitous labor, and fetal death have been reported. The procedure should be performed in centers with extensive experience and surgical back-up; if it is undertaken after 26 weeks of pregnancy, obstetric standby should be available in case of premature labor. Transcatheter aortic valve implantation is not routinely performed in pregnant women, but may be considered in select situations. Cardiac surgery during pregnancy is seldom necessary and should be avoided whenever possible. A higher risk of fetal malformation and loss has been documented when cardiopulmonary bypass is performed in the first trimester; if it is performed in the last trimester, the likelihood of precipitating premature labor is greater. Later in the third trimester, delivery can be performed prior to cardiac surgery if there is adequate fetal maturity. From a fetal outcome perspective, the optimal time for maternal cardiac surgery during pregnancy is likely between 20 and 28 weeks of gestation. Fetal outcomes may also be improved by use of normothermic rather than hypothermic extracorporeal circulation, higher pump flows, higher pressures, and as short a bypass time as possible. Obstetric monitoring of the fetus during the procedure is recommended so that fetal bradycardia may be dealt with promptly and uterine contractions may be controlled. In the current era, with the interventions outlined above, cardiothoracic surgery of the mother can be performed with relative safety during pregnancy, with a maternal mortality rate similar to that in a nonpregnant woman unless the surgery is emergent. However, fetal complications (prematurity and death) are increased in association with urgent high-risk surgery, maternal comorbidity, and early 17 gestational age. A multidisciplinary approach is important to optimize the outcome for both mother and baby. Labor and Delivery The hemodynamic changes that occur at the time of labor and delivery mandate that for the high-risk patient with cardiac disease, a multidisciplinary approach during labor and delivery be used. The cardiologist and the obstetrician should work with the anesthesiologist to determine the safest mode of delivery. For most patients with cardiac disease, a vaginal delivery is feasible and preferable because it 18 is associated with fewer complications.