Genome assembly and phylogenomic data analyses using plastid data: Contrasting species tree estimation methods.

Phylogenomics has become increasingly popular in recent years mostly due to the increased affordability of next generation sequencing techniques. Phylogenomics has sparked interest in multiple fields of research, including systematics, ecology, epidemiology, and even personalized medicine, agriculture and pharmacy. Despite this trend, it is usually difficult to learn and understand how the analyses were done, how the results were obtained, and most importantly, how to replicate the study. Here we present the data and all of the code utilized to perform phylogenomic inferences using plastome data: from raw data to extensive phylogenetic inference and accuracy assessment. The data presented here utilizes plastome sequences available on GenBank (accession numbers of 94 species are available below) and the code is also available at https://github.com/deisejpg/rosids. Gonçalves et al. is the research article associated with the data analyses presented here.

Scalloped tongue is associated with nocturnal intermittent hypoxia among community-dwelling Japanese: the Toon Health Study.

Scalloped tongue is considered as a possible clinical finding of obstructive sleep apnoea (OSA). There are few evidence of the association between scalloped tongue and OSA. To examine the association between scalloped tongue and nocturnal intermittent hypoxia (NIH), a surrogate marker of OSA, among a general Japanese population. Study participants were 398 men and 732 women aged 30-79 years who participated in the Toon Health Study from 2011 to 2014. Scalloped tongue was classified into three categories: none, mild and moderate-to-severe. Moderate-to-severe NIH was defined as the 3% oxygen desaturation index of ≥15 events/h during sleep for one night with pulse oximetry. The multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for moderate-to-severe NIH were calculated according to scalloped tongue categories using a logistic regression model. There were 69 (6·1%) moderate-to-severe NIH cases in this population. The multivariable-adjusted ORs (95% CIs) of moderate-to-severe NIH were 1·59 (0·85-2·95) for mild and 2·39 (1·10-5·17) for the moderate-to-severe scalloped tongue group compared with the group without scalloped tongues. When stratified by overweight status (BMI <25 or ≥25 kg m-2 ), the respective ORs (95% CIs) were 2·83 (1·06-7·55) and 4·74 (1·28-17·49) among overweight individuals, and 0·94 (0·40-2·70) and 1·52 (0·57-4·05) among non-overweight individuals. Scalloped tongue was associated with higher prevalence of moderate-to-severe NIH among the general Japanese population and this association was more evident in overweight individuals.

Alkaline-earth phosphonate MOFs with reversible hydration-dependent fluorescence.

A new rigid tritopic phosphonic ligand, 2,4,6-tris(4-phosphonophenyl)pyridine (H6L), was synthesized and used to assemble isostructural barium (1) and strontium (2) phosphonate metal organic frameworks that exhibit fully reversible and selective water-dependent fluorescence red-shift at room temperature.

Impact of damming on the Chironomidae of the upper zone of a tropical run-of-the-river reservoir / Impacto de um represamento sobre Chironomidae do remanso de um reservatório fio água tropical

Abstract We examined the effects of the Mogi-Guaçu river damming (São Paulo State, Brazil) on the Chironomidae fauna. Pre, during, and post-filling sampling was carried out in the main channel and margins of one site in the upper zone of the reservoir, using a modified Petersen grab (325 cm2). We evaluated the total, subfamily, and tribe densities and also their relative abundance. Analysis of genera included densities, relative abundance, richness, and dominance. The Rosso’s ecological value index (EVI) determined the ecological importance of each genus. There was a tendency of decrease of the total Chironomidae density, increase in the percentage of Chironomini, and decrease in densities and percentages of Orthocladiinae and Tanytarsini. These changes in percentage were respectively related to Polypedilum, Lopescladius, and Rheotanytarsus, the genera with the highest EVI values. After-filling richness was lower in the margins and dominance of genera did not change significantly. Chironomidae in the margins was more sensitive to damming than in the main channel. This difference in sensibility sustains the use of Chironomidae as bioindicators. Damming impact was indicated by the reduction of both genera richness in the margins and relative abundance of groups typical of faster waters. The results have highlighted the need for multi-habitat analysis combined with a before-after sampling approach in the environmental impact studies concerning the damming impact on the benthic fauna.

Resumo Este trabalho teve como objetivo avaliar o impacto do represamento do Rio Mogi-Guaçu, em um ponto situado na zona de remanso do reservatório, através da utilização da taxocenose Chironomidae. A amostragem foi realizada antes, durante e após o represamento, no canal e nas margens, com o auxílio de um pegador Petersen modificado (área de 325 cm2). Calculou-se a densidade total, de subfamílias, tribos e gêneros de Chironomidae, bem como sua abundância relativa. Estimou-se a riqueza e a dominância de gêneros. O índice de valor ecológico de Rosso (IVE) foi utilizado para avaliar a importância ecológica dos diferentes gêneros. Houve tendência de redução da densidade total de Chironomidae, aumento da abundância relativa de Chironomini e diminuição das abundâncias relativas de Orthocladiinae e Tanytarsini. Estas alterações de abundância relativa foram relacionadas respectivamente a Polypedilum, Lopescladius e Rheotanytarsus, gêneros que apresentaram os maiores valores de IVE. Após o represamento, houve decréscimo da riqueza de gêneros na margem, enquanto a dominância não apresentou alteração significativa. A taxocenose de Chironomidae das margens mostrou-se mais sensível ao represamento que a do canal. Esta diferença de sensibilidade confirma o potencial dos Chironomidae como bioindicadores. A ocorrência de impacto foi observada através da diminuição da riqueza de gêneros nas margens e da abundância relativa de táxons característicos de águas mais rápidas. Os resultados chamam atenção para a necessidade de utilizar a abordagem de múltiplos habitats combinada com a amostragem antes e depois do evento na avaliação dos impactos causados por represamento sobre a fauna bentônica.

Impact of damming on the Chironomidae of the upper zone of a tropical run-of-the-river reservoir.

We examined the effects of the Mogi-Guaçu river damming (São Paulo State, Brazil) on the Chironomidae fauna. Pre, during, and post-filling sampling was carried out in the main channel and margins of one site in the upper zone of the reservoir, using a modified Petersen grab (325 cm2). We evaluated the total, subfamily, and tribe densities and also their relative abundance. Analysis of genera included densities, relative abundance, richness, and dominance. The Rosso's ecological value index (EVI) determined the ecological importance of each genus. There was a tendency of decrease of the total Chironomidae density, increase in the percentage of Chironomini, and decrease in densities and percentages of Orthocladiinae and Tanytarsini. These changes in percentage were respectively related to Polypedilum, Lopescladius, and Rheotanytarsus, the genera with the highest EVI values. After-filling richness was lower in the margins and dominance of genera did not change significantly. Chironomidae in the margins was more sensitive to damming than in the main channel. This difference in sensibility sustains the use of Chironomidae as bioindicators. Damming impact was indicated by the reduction of both genera richness in the margins and relative abundance of groups typical of faster waters. The results have highlighted the need for multi-habitat analysis combined with a before-after sampling approach in the environmental impact studies concerning the damming impact on the benthic fauna.

The effects of anion variation and ligand derivatization on silver coordination networks based upon weaker interactions.

This article presents a series of silver(I) coordination networks based upon nonchelating bidentate thioether ligands. Frameworks using AgOTs as the silver(I) starting material form two-dimensional frameworks and are quite stable as shown by differential scanning calorimetry/thermogravimetric analysis (DSC/TGA) data. The networks are sufficiently robust as to maintain the same layered motif when the basic skeleton of the ligand is sequentially derivatized with -OEt, OBu, and OHex groups. Crystal structures of the AgOTs complexes of the underivatized and bis(hexoxy) derivatives, compounds 5 and 8, respectively, are presented as well as powder X-ray diffraction (PXRD) data of the other complexes. For 5, C20H20S3O3Ag, crystal data are as follows: monoclinic, space group P2(1)/n, a = 11.8117(5) A, b = 7.8813(5) A, c = 22.3316(10) A, beta = 102.245(5) degrees, V = 2031.6(2) A(3), Z = 4. For 8, C30H44S3O6Ag, crystal data are as follows: triclinic, space group Ponebar a = 8.445(4) A, b = 10.855(5) A, c = 19.308(9) A, alpha = 84.53(1) degrees, beta = 78.76(1) degrees, gamma = 68.43(1) degrees V = 1613.9(13) A(3), Z = 2. Changing the silver(I) starting material to AgPF6 results in a shift to a one-dimensional structure, 9, as shown by X-ray crystallography and in highly compromised stability. For 9, C14H16S2N2PF6Ag, crystal data are as follows: monoclinic, space group P2/n, a = 11.9658(11) A, b = 3.9056(4) A, c = 19.6400(18) A, beta = 92.87(1) degrees, V = 916.70(15) A(3), Z = 4.

Highly selective guest uptake in a silver sulfonate network imparted by a tetragonal to triclinic shift in the solid state.

The silver sulfonate network presented herein, silver 3-pyridinesulfonate, reversibly and selectively absorbs MeCN while undergoing a major structural rearrangement. The origin of this structural flexibility is a coupling of the weak coordinating ability of the SO3 group with the geometrically pliant silver(I) center. Single crystal and powder X-ray structures of both the desolvated and solvated forms are presented in addition to the mechanism of their reversible interconversion. A heterogeneous gas chromatographic study showing selective extraction of the MeCN is also presented. Extended solid frameworks which reorder to any extent are not common but the structure presented herein transforms from a tetragonal to a triclinic crystal system. The results indicate that cooperative interactions in systems based on supposedly weaker interactions can yield softer yet functional networks with behavior unlike that observed in more rigid inorganic frameworks.

Force pattern of hypoxic myocardium applied to oxygenated muscle preparations: comparison with effects of regional ischemia on the contraction of non-ischemic myocardium.

OBJECTIVE: To examine the basis for local wall motion abnormalities commonly seen in patients with ischemic heart disease, computer-controlled isolated muscle studies were carried out. METHODS: Force patterns of physiologically sequenced contractions (PSCs) from rat left ventricular muscle preparations under well-oxygenated conditions and during periods of hypoxia and reoxygenation were recorded and stored in a computer. Force patterns of hypoxic-reoxygenating and oxygenated myocardium were applied to oxygenated and hypoxic-reoxygenating myocardium, respectively. RESULTS: Observed patterns of shortening and lengthening closely resemble those obtained from ischemic and non-ischemic myocardial segments using ultrasonic crystals in intact dog hearts during coronary occlusion and reperfusion, and are similar to findings reported in angiographic studies of humans with coronary artery disease. CONCLUSION: The current study, demonstrating motions of oxygenated isolated muscle preparations which are similar to those in perfused segments of intact hearts with regional ischemia, supports the concept that the multiple motions of both ischemic and non-ischemic segments seen in regional myocardial disease can be explained by interactions of strongly and weakly contracting muscle during the physiologic cardiac cycle.

Postparturient change in endotoxin levels of ruminal fluid and serum in dairy cows.

The changes in the endotoxin levels of ruminal fluid and serum in postparturient cows were evaluated. Five cows were fed hay and concentrates on an individual basis (farm A) and the other 5 cows were given complete feed ad libitum (farm B) after parturition. Ruminal pH levels decreased in both groups after parturition. Subsequently, the ruminal endotoxin levels increased with the declining pH on both of the farms. The ruminal endotoxin levels were slightly higher in cows of farm B than those of farm A. Serum endotoxin levels also showed episodic fluctuations, however, there were no parallel changes between the endotoxin levels of the ruminal fluid and sera.

Sclerosing stromal tumour in a cow.

A case of sclerosing stromal tumour in an 8-year-old cow is described. The left ovary was entirely replaced by neoplastic tissue, whose features were pseudolobulation of cellular areas, intercellular oedema and calcified plaques. The neoplastic cells varied in morphology and were similar to ovarian stromal cells, theca cells or lutein cells. Immunohistochemically, S-100 protein, oestradiol and testosterone were detected in theca-like or luteinized cells, some of which had ultrastructural features suggestive of steroid hormone synthesis. In contrast, desmin and actin characterized slender spindle cells. This is the first report of a sclerosing stromal tumour in cattle.

Empiric determination of the transition from concentric hypertrophy to congestive heart failure in essential hypertension.

OBJECTIVES: Our aim was to determine whether there is a final transition from left ventricular hypertrophy to congestive heart failure in the late stage of essential hypertension. BACKGROUND: A theoretic model using the concept of systolic transmural nonuniform wall thickening was applied to develop a concentric two-shell geometry allowing evaluation of the mechanics of circumferential midwall fibers. METHODS: We evaluated pressure-volume data from 46 normal control subjects (control group) and 70 patients with hypertension: 33 without hypertrophy (hypertension only group), 14 with hypertrophy (hypertrophy group) and 23 with heart failure in addition to hypertrophy (heart failure group). RESULTS: End-diastolic volume index was higher in the heart failure group than in the control group (p < 0.01). Although left ventricular wall thickness and mass index were increased in both the hypertrophy and the heart failure group, concentricity indexes as assessed by ratios of left ventricular wall thickness to dimension and mass index to end-diastolic volume index were maximal in the former. Although endocardial and standard midwall fractional shortening did not differ among the control, hypertension only and heart failure groups, that of the modified midwall by concentric two-shell geometry was decreased in the hypertrophy and the heart failure groups (p < 0.05). The Hotelling T2 test and Mahalanobis distance clearly discriminated the latter two groups with end-systolic stress and modified midwall fractional shortening relation. CONCLUSIONS: A fitting segmented regression model predicted a progression to hypertrophy and identified a transition from hypertrophy to heart failure by a combination of modified midwall fractional shortening and concentricity indexes.

Histopathological findings of the digits in dairy cows in Japan.

Two hundred and thirty-nine digits of 45 Holstein dairy cows, which were raised in typical Japanese dairy farms and received poor hoof management, were randomly obtained in the slaughterhouses and examined histopathologically. The findings were classified into 5 grades on the basis of the severity of circulatory disturbances and of keratogenesis. The lesions from Grade 1 to 5 were considered as manifestations of serial lesions indicating that subclinical laminitis advanced to other hoof lesions. The incidence of Grade 2, regarded as subclinical laminitis, reached approximately 50% of digits examined. The lesions classified as Grades 3 (23.9%) and 4 (5.4%) were mainly characterized by circulatory disturbances, which were similar to those of chronic laminitis in the previous reports. The incidence of Grade 5, characterized by sole ulcer, was 5.4%. It is suggested that a considerable number of daily cows in Japan suffered from subclinical laminitis, which may be the cause of recent high incidence of hoof diseases in dairy cows.

Prominent negative T waves with QT prolongation indicate reperfusion injury and myocardial stunning.

To observe the clinical course after reperfusion and recovery from myocardial stunning of the left ventricular anterior wall, we prospectively reviewed and analyzed cardiac enzymes, ECG changes, echocardiograms, and cineangiograms in 8 patients with the acute ischemic syndrome who fulfilled the following criteria: 1) no history of previous myocardial infarction, 2) repeated and/or prolonged episodes of chest pain, 3) critical stenosis of the left anterior descending artery with wall motion abnormalities, 4) successful emergency percutaneous transluminal coronary angioplasty, and 5) normal wall motion on repeat cineangiography 4 to 8 weeks later. Creatine kinase (CK) and/or its cardiac isoenzyme (CK-MB) were minimally elevated in all cases. Wall motion was normalized with the reduction of end-systolic volume (end-diastolic volume: from 139 +/- 25 to 140 +/- 37 ml, ns, end-systolic volume: from 68 +/- 16 to 39 +/- 13 ml, p < 0.001, ejection fraction: from 51 +/- 6 to 71 +/- 6%, p < 0.001). Serial echocardiograms showed normalization of wall motion within 4 to 28 days. T wave inversion in the left precordial leads developed 30 min to 5 hours after the cessation of chest pain or successful reperfusion, and prominent negative T waves (1.6 +/- 0.6 mV) with QT prolongation (0.56 +/- 0.08 sec) in V3 or V4 reached their peak values within one to 5 days. ECG abnormalities resolved after 21 to 95 days. These ECG findings may indicate reperfusion injury and the presence of myocardial stunning in the anterior wall of the left ventricle.

Left ventricular midwall mechanics in systemic arterial hypertension. Myocardial function is depressed in pressure-overload hypertrophy.

BACKGROUND: Left ventricular (LV) midwall geometry has been described conventionally as the sum of the chamber radius and half of the wall thickness; this convention is based on the assumption of uniform transmural thickening during systole. However, theoretical considerations and experimental data indicate that the inner half (inner shell) of the LV wall thickens more than the outer half (outer shell). Thus, an end-diastolic circumferential midwall fiber exhibits a relative migration toward the epicardium during systole. As a result, the conventional method provides an overestimate of the extent of the midwall fiber shortening. METHODS AND RESULTS: We developed an ellipsoidal model with a concentric two-shell geometry (nonuniform thickening) to assess midwall fiber length transients throughout the cardiac cycle. This modified midwall method was used in the analysis of LV cineangiograms from 15 patients with systemic arterial hypertension and 14 normal subjects. Study groups were classified according to LV mass index (LVMI): 14 normal subjects (group I), eight hypertensive patients with a normal LVMI (group II), and seven hypertensive patients with an increased LVMI (group III). There were no significant differences in LV end-diastolic pressure or volume among the three groups; the ejection fraction was slightly greater in group II (70 +/- 5%) than in groups I (65 +/- 8%) and III (66 +/- 4%), but this trend did not achieve statistical significance. Values for endocardial and conventional midwall fractional shortening (FS) were also similar in the three groups. By contrast, FS by the concentric two-shell geometry (modified midwall method) in group III (16 +/- 2%) was significantly less than that seen in groups I and II (21 +/- 4% and 21 +/- 5%, respectively; both p less than 0.05). This difference achieves greater importance when it is recognized that mean systolic circumferential stress was lower in group III (151 +/- 22 g/cm2) than in groups I and II (244 +/- 37 g/cm2 and 213 +/- 38 g/cm2, respectively; both p less than 0.01). The midwall stress-shortening coordinates in six of the seven group III patients were outside the 95% confidence limits for the normal (group I) subjects. Thus, despite a normal ejection fraction, systolic function is subnormal in hypertensive patients with LV hypertrophy. CONCLUSIONS: Chamber dynamics provide an overestimate of myocardial function, especially when LV wall thickness is increased. This is due to a relatively greater contribution of inner shell thickening in pressure-overload hypertrophy.

Clinical assessment of left ventricular systolic function by force-length and stress-shortening relationships.

Left ventricular (LV) systolic function was assessed in patients with hypertensive heart disease (HHD, n = 30), hypertrophic cardiomyopathy (HCM, n = 27), dilated cardiomyopathy (DCM, n = 25), volume overload heart (VOH, n = 31) and normal subjects (NS, n = 32) in the two-dimensional framework of force-length (end-systolic stress-end-systolic volume index) and stress-shortening (mid-systolic stress-ejection fraction). Quadratic discriminant analysis revealed that the ellipses of confidence of HHD and normal subjects were in the same place with regard to both force-length and stress-shortening, while all other groups were well-discriminated. Three subgroups of patients, those with DCM with mild heart failure and those with VOH (with and without heart failure), were easily distinguishable on the basis of stress-shortening, but not on the basis of force-length measurements. It is concluded that LV systolic function and afterload are maintained within the normal range under pressure and volume overload until symptoms of heart failure appear via the mechanism of compensatory hypertrophy. Stress-shortening appears to be a more useful parameter than force-length for the analysis of LV systolic function in clinical practice.

Square root sign of left ventricular diastolic pressure curve in atrial septal defect.

The square root (dip and plateau) sign was observed in 7 of 21 adult patients with atrial septal defect (ASD). This study evaluated left ventricular (LV) diastolic filling dynamics and hemodynamic findings in 7 patients (Group 1) with, and 14 patients (Group 2) without the square root sign; 10 normal subjects (Group 3) served as controls. No significant differences were observed in LV end-diastolic and end-systolic volumes, ejection fraction, or left to right shunt. In Group 1, 77% of LV filling was completed in the first half of diastole; this percentage was 49% and 53% in Groups 2 and 3, respectively (both p less than 0.01 versus Group 1). Early diastolic filling velocity (at 20% of diastole) in Group 1 was significantly greater, and late diastolic filling velocity (at 80% and 90% of diastole) was reduced in Group 1 compared to those in Groups 2 and 3 (all p less than 0.05). The average values for right and left ventricular end-diastolic pressures were significantly higher in Group 1 (11 +/- 2 and 10 +/- 4 mmHg, p less than 0.05) than Group 2 (7 +/- 2 and 7 +/- 2 mmHg, p less than 0.05). It is suggested that a constrictive pathophysiology due to 4 chambers interaction or right ventricular constraint may play a role in the genesis of the square root sign in ASD.

Spectrum of restrictive cardiomyopathy: report of the national survey in Japan.

This report describes clinical profiles and echocardiographic, hemodynamic, and histologic findings in 26 cases of idiopathic RCM based on the diagnostic criteria of (1) heart failure resulting from a stiff left ventricle, (2) normal LV size and systolic function, (3) absence of LV hypertrophy, and (4) cause or association unknown. There were 14 male and 12 female patients ranging in age from 5 to 63 years. Ten patients died during the mean follow-up period of 145 months, and five died of heart failure after 10 years. Three had a family history of HCM. Thromboembolism was observed in eight. Echocardiograms showed normal LV wall thickness and contraction. Hemodynamic characteristics included elevated biventricular filling pressures and a pulmonary wedge pressure that was usually higher than the right atrial pressure. Equalization of biventricular filling pressures was seen, however, in almost all patients with severe tricuspid regurgitation (seven of eight). The square root sign was seen in 50% in RV diastolic pressure tracings and 28% in LV tracings. This sign was observed in patients with elevated filling pressures. Interstitial fibrosis (22 of 23), endocardial thickening (13 of 23), and myofibrillar hypertrophy (10 of 23) were common histologic findings. Severe myocardial fiber disarray consistent with HCM was seen in four patients.

An assessment of left ventricular systolic function in pressure and volume overload heart with two shell compartment model of ellipsoid revolution.

Left ventricular (LV) midwall mechanics were evaluated in normal, pressure overload due to hypertension, and volume overload hearts due to aortic (AR) and mitral regurgitations (MR) using a 2 shell compartment model of ellipsoid revolution. While ejection fraction (EF) was in the normal range, midwall fractional shortening (MFS) was depressed with low end-diastolic and end-systolic stress in hypertrophied hearts with pressure overload. Not only LV volumes but also LV systolic pressure and wall thickness were increased in AR. LV end-diastolic pressure was elevated, and EF and MFS were reduced in patients with AR and congestive heart failure (CHF). In patients with MR and CHF, pulmonary capillary wedge pressure was elevated, LV volumes were enlarged and end-systolic stress was high, but LV wall thickness and MFS remained in the normal range. It is concluded from this observation that: 1) myocardial contractility is already depressed with normal systolic function in hypertrophied ventricle with pressure overload. 2) AR can be considered to be the disease of both pressure and volume overload, and symptoms of CHF are the result of depressed myocardial contractility. 3) MR is the disease of pure volume overload. Myocardial contractility is well preserved even with the presence of severe CHF in MR.

Optimal timing for valve replacement in chronic aortic regurgitation: analysis based on the myocardial contractility and postoperative prognosis.

Left ventricular (LV) function was evaluated considering force-velocity and stress-shortening relationships in 14 asymptomatic (Group 1), 18 symptomatic patients (Group 2), and 53 normal subjects (Group 3) to determine the optimal time for valve replacement in patients with chronic aortic regurgitation (AR). Valve replacement was recommended for all Group 2 patients and for one patient in Group 1, who had sustained ventricular tachycardia. There was one operative death and five deaths remote from surgery; one patient in Group 1 died suddenly of undetermined cause, and four patients in Group 2 died of congestive heart failure (CHF). The LV end-systolic volume index (ESVI) was greater than 100 ml/m2 in the five patients whose death was unrelated to surgery (remote deaths). ESVI was less than 50 ml/m2 in all but two patients in Group 1, and more than 40 ml/m2 in all cases in Group 2. The index of preload, end-diastolic stress (sigma ed), was increased in Groups 1 and 2 as compared with Group 3. A significant positive correlation was observed between end-systolic stress (sigma es) and ESVI (r = 0.71, p less than 0.001) in patients with AR, and this linear line was not as steep as that of Group 3. Afterload (sigma es) and ejection fraction (EF) in Group 1 were within normal range, afterload was normal but EF was reduced in mildly symptomatic patients in Group 2, and severely symptomatic patients had markedly reduced EF and elevated afterload. There was a close correlation between ESVI and end-diastolic volume index (EDVI), and this was expressed as an exponential curve (Y = 21.69e0.006x, r = 0.88, p less than 0.001). This indicates that the rate of shortening of the muscle fiber deteriorates exponentially with enlargement of the ventricle. These observations suggest that in AR patients: 1) afterload and contractility of the ventricle remain normal in the majority of asymptomatic patients by means of compensatory hypertrophy and preload elevation (preload reserve), 2) deterioration of contractility seems to be the factor initiating CHF, and 3) progression of CHF is due to further deterioration of contractility in addition to elevation of afterload (afterload mismatch). It is concluded that careful observations are necessary when ESVI exceeds 50 ml/m2 in asymptomatic patients. Valve replacement is recommended when such patients develop symptoms of CHF, or either when EF falls to less than 50% or ESVI exceeds 100 ml/m2, even if patients remain asymptomatic.