Onset Of Decompensation Research Articles

Rejuvenating bone marrow hematopoietic reserve prevents regeneration failure and hepatic decompensation in animal model of cirrhosis.

Bone marrow stem cells (BM-SCs) and their progeny play a central role in tissue repair and regeneration. In patients with chronic liver failure, bone marrow (BM) reserve is severally compromised and they showed marked defects in the resolution of injury and infection, leading to liver failure and the onset of decompensation. Whether BM failure is the cause or consequence of liver failure during cirrhosis is not known. In this study, we aimed to determine the underlying relationship between BM failure and regeneration failure in cirrhosis. C57Bl/6(J) mice were used to develop chronic liver injury through intra-peritoneal administration of carbon tetrachloride (CCl4) for 15 weeks (0.1-0.5 ml/kg). Animals were sacrificed to study the transition of cirrhosis and BM defects. To restore the BM-SC reserve; healthy BM cells were infused via intra-BM infusion and assessed for changes in liver injury, regeneration, and BM-SC reserve. Using a CCl4-induced animal - model of cirrhosis, we showed the loss of BM-SCs reserve occurred before regeneration failure and the onset of non-acute decompensation. Intra-BM infusion of healthy BM cells induced the repopulation of native hematopoietic stem cells (HSCs) in cirrhotic BM. Restoring BM-HSCs reserve augments liver macrophage-mediated clearance of infection and inflammation dampens neutrophil-mediated inflammation, accelerates fibrosis regression, enhances hepatocyte proliferation, and delays the onset of non-acute decompensation. These findings suggest that loss of BM-HSCs reserve underlies the compromised innate immune function of the liver, drives regeneration failure, and the onset of non-acute decompensation. We further provide the proof-of-concept that rejuvenating BM-HSC reserve can serve as a potential therapeutic approach for preventing regeneration failure and transition to decompensated cirrhosis.

Development and validation of an ensemble machine learning framework for detection of all-cause advanced hepatic fibrosis: a retrospective cohort study

Cirrhosis is the result of advanced scarring (or fibrosis) of the liver, and is often diagnosed once decompensation with associated complications has occurred. Current non-invasive tests to detect advanced liver fibrosis have limited performance, with many indeterminate classifications. We aimed to identify patients with advanced liver fibrosis of all-causes using machine learning algorithms (MLAs). In this retrospective study of routinely collected laboratory, clinical, and demographic data, we trained six MLAs (support vector machine, random forest classifier, gradient boosting classifier, logistic regression, artificial neural network, and an ensemble of all these algorithms) to detect advanced fibrosis using 1703 liver biopsies from patients seen at the Toronto Liver Clinic (TLC) between Jan 1, 2000, and Dec 20, 2014. Performance was validated using five datasets derived from patient data provided by the TLC (n=104 patients with a biopsy sample taken between March 24, 2014, and Dec 31, 2017) and McGill University Health Centre (MUHC; n=404). Patients with decompensated cirrhosis were excluded. Performance was benchmarked against aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), transient elastography, and an independent panel of five hepatology experts (MB, GS, HK, KP, and RSK). MLA performance was evaluated using the area under the receiver operating characteristic curve (AUROC) and the percentage of determinate classifications. The best MLA was an ensemble algorithm of support vector machine, random forest classifier, gradient boosting classifier, logistic regression, and neural network algorithms, which achieved 100% determinate classifications (95% CI 100·0-100·0), an AUROC score of 0·870 (95% CI 0·797-0·931) on the TLC validation set (fibrosis stages F0 and F1 vs F4), and an AUROC of 0·716 (95% CI 0·664-0·766) on the MUHC validation set (fibrosis stages F0, F1, and F2 vs F3 and F4). The ensemble MLA outperformed all routinely used biomarkers and achieved comparable performance to hepatologists as measured by AUROC and percentage of indeterminate classifications in both the TLC validation dataset (APRI AUROC score 0·719 [95% CI 0·611-0·820], 83·7% determinate [95% CI 76·0-90·4]; FIB-4 AUROC score 0·825 [95% CI 0·730-0·912], 72·1% determinate [95% CI 63·5-80·8]) and the MUHC validation dataset (APRI AUROC score 0·618 [95% CI 0·548-0·691], 75·5% determinate [95% CI 71·5-79·2]; FIB-4 AUROC score 0·717 (95% CI 0·652-0·776), 75·5% determinate [95% CI 0·713-0·797]), and achieving only slightly lower AUROC than transient elastography (0·773 [95% CI 0·699-0·834] vs 0·826 [95% CI 0·758-0·889]). We have shown that an ensemble MLA outperforms non-imaging-based methods in detecting advanced fibrosis across different causes of liver disease. Our MLA was superior to APRI, FIB-4, and NFS with no indeterminate classifications, while achieving performance comparable to an independent panel of experts. MLAs using routinely collected data could identify patients at high-risk of advanced hepatic fibrosis and cirrhosis among patients with chronic liver disease, allowing intervention before onset of decompensation. Toronto General Hospital Foundation.

Predictors of hemodynamic decompensation in progressive hypovolemia: Compensatory reserve versus heart rate variability.

Hemorrhage remains the leading cause of death following traumatic injury in both civilian and military settings. Heart rate variability (HRV) and heart rate complexity (HRC) have been proposed as potential "new vital signs" for monitoring trauma patients; however, the added benefit of HRV or HRC for decision support remains unclear. Another new paradigm, the compensatory reserve measurement (CRM), represents the integration of all cardiopulmonary mechanisms responsible for compensation during relative blood loss and was developed to identify current physiologic status by estimating the progression toward hemodynamic decompensation. In the present study, we hypothesized that CRM would provide greater sensitivity and specificity to detect progressive reductions in central circulating blood volume and onset of decompensation as compared with measurements of HRV and HRC. Continuous, noninvasive measurements of compensatory reserve and electrocardiogram signals were made on 101 healthy volunteers during lower-body negative pressure (LBNP) to the point of decompensation. Measures of HRV and HRC were taken from electrocardiogram signal data. Compensatory reserve measurement demonstrated a superior sensitivity and specificity (receiver operator characteristic area under the curve [ROC AUC] = 0.93) compared with all HRV measures (ROC AUC ≤ 0.84) and all HRC measures (ROC AUC ≤ 0.86). Sensitivity and specificity values at the ROC optimal thresholds were greater for CRM (sensitivity = 0.84; specificity = 0.84) than HRV (sensitivity, ≤0.78; specificity, ≤0.77), and HRC (sensitivity, ≤0.79; specificity, ≤0.77). With standardized values across all levels of LBNP, CRM had a steeper decline, less variability, and explained a greater proportion of the variation in the data than both HRV and HRC during progressive hypovolemia. These findings add to the growing body of literature describing the advantages of CRM for detecting reductions in central blood volume. Most importantly, these results provide further support for the potential use of CRM in the triage and monitoring of patients at highest risk for the onset of shock following blood loss.

Measures of Compensatory Reserve are More Sensitive and Specific than Heart Rate Variability as Early Predictors of Hemodynamic Decompensation

BackgroundHemorrhage remains the leading cause of death following traumatic injury in both civilian and military settings. Heart rate variability (HRV) and complexity (HRC) have been recognized as potential “new vital signs” for monitoring trauma patients, although their benefit for triage decision support remains unclear. Another new paradigm, the compensatory reserve measurement (CRM), represents the integration of all mechanisms responsible for compensation during blood loss, designed to identify current physiologic status by estimating the progression toward hemodynamic decompensation. We hypothesized that CRM would provide greater sensitivity and specificity to detect progressive reductions in central circulating blood volume and onset of decompensation as compared to measurements of HRV and HRC.MethodsContinuous, noninvasive measurements of CRM and electrocardiogram (ECG) were made on 101 healthy volunteers (59 males, 42 females; mean±SD age 28±8 years) during stepwise progressive central hypovolemia to the point of decompensation. Lower body negative pressure (LBNP) was used to simulate hemorrhage by inducing the onset and progression of central hypovolemia. Time‐domain measures of HRV were taken from ECG signal data including R‐to‐R Interval Standard Deviation in milliseconds (ms), Root Mean Square Standard Deviation, percentage of RRI that vary by at least 50 ms, and amplitude measures of High Frequency Oscillations and Low Frequency Oscillations (CDMLF) obtained from the complex demodulation method. Measures of HRC included Sample Entropy, Fractal Dimension by Dispersion Analysis, Stationarity and Detrended Fluctuation Analysis. Data were analyzed using generalized estimating equations with compound symmetry covariance structures for longitudinal correlated data analysis of continuous variables, the results of which were used to report least‐square means with 95% confidence intervals at each LBNP level.ResultsCRM demonstrated superior ROC AUC (0.93) compared with all measures of HRV (≤ 0.84), and HRC (≤ 0.86). Sensitivity and specificity values at the ROC optimal thresholds were greater for CRM (SENS=0.84; SPEC=0.84) than HRV (SENS ≤ 0.78; SPEC ≤ 0.77) and HRC (SENS ≤ 0.79; SPEC ≤ 0.77). With standardized values across all levels of LBNP, CRM had a steeper decline, less variability, and explained a greater proportion of the variation in the data than both HRV and HRC during progressive hypovolemia.ConclusionConsistent with our hypothesis, CRM had greater sensitivity and specificity in detecting progressive reductions in circulating blood volume and decompensation than HRV and HRC. These findings add to the growing body of literature describing the advantages of CRM for detecting reductions in central blood volume. Most importantly, these results provide further support for the potential use of CRM in the triage and monitoring of patients at risk of circulatory shock following blood loss.Support or Funding InformationStudy funding was provided by a grant from the US Army Combat Casualty Care Research Program (D‐009‐2014‐USAISR).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Patient Views on Advance Care Planning in Cirrhosis: A Qualitative Analysis.

Aim To investigate patient experiences and perceptions of advance care planning (ACP) process in cirrhosis. Methods Purposive sampling was used to identify and recruit participants (N = 17) from discrete patient groups: compensated with no prior decompensation, decompensated and not yet listed for transplant, transplant wait listed, medical contraindications for transplant, and low socioeconomic status. Review and discussion of local ACP videos, documents, and experiences with ACP occurred in two individual interviews and four focus groups. Data were analyzed using inductive content analysis including iterative processes of open coding, categorization, and abstraction. Results Three overarching categories emerged: (1) lack of understanding about disease trajectories and ACP processes, (2) roles of alternate decision makers, and (3) preferences for receiving ACP information. Most patients desired advanced care-planning conversations before the onset of decompensation (specifically hepatic encephalopathy) with a care provider with whom they had a trusting, preexisting relationship. Involvement of the alternate decision makers was of critical importance to participants, as was the use of direct, easy to understand patient education tools that address practical issues. Conclusion Our findings support the need for early advance care planning in the outpatient setting. Outpatient clinicians may play a key role in facilitating these discussions.

Effects of Virologic Response to Treatment on Short- and Long-term Outcomes of Patients With Chronic Hepatitis B Virus Infection and Decompensated Cirrhosis

Little is known about the effects of antiviral therapy on short- and long-term survival of patients with hepatitis B virus (HBV)-related decompensated cirrhosis. We aimed to determine whether a maintained virologic response (MVR, defined as persistent undetectable HBV DNA during therapy) associates with short-term (6 mo) and long-term (6-120 mo) survival of patients with decompensated cirrhosis. We performed a 10-year observation analysis using data from the Epidemiology and Natural History of Liver Cirrhosis study of patients with decompensated liver cirrhosis in Korea. Of the entire cohort (1595 patients enrolled at onset of decompensation since 2005), our analysis comprised 295 patients who immediately began treatment with entecavir (n= 179) or lamivudine (n= 116) after decompensation. We collected laboratory test results, data on hepatocellular carcinoma (HCC) development, and Child-Turcotte-Pugh and model for end-stage liver disease (MELD) scores. The mean follow-up time was 62.3 ± 36.5 months. The primary end point was time of liver transplant-free survival. The median survival time was 7.7 years; 60.1% of patients survived for 5 years and 45.7% survived for 10 years without liver transplantation. An MVR was observed in 116 patients (39.3%); these patients had significantly longer times of transplant-free survival than patients without MVR. Survival times associated with the occurrence of HCC; survival of patients without HCC was excellent if they survived the first 6 months after initiation of antiviral therapy, whereas the survival rates of patients with HCC decreased persistently over time. A baseline MELD score above 20 and multiple complications were associated with short-term mortality. MVR was the factor most strongly associated with long-term transplant-free survival. Significantly higher proportions of patients who received entecavir survived 10 years compared with patients who received lamivudine, but no difference was observed among patients with MVRs. Patients with MVRs had significant improvement in hepatic function over time, but nonsignificant reductions in risk of HCC or HCC-related mortality. In a 10-year observation study of patients in Korea with HBV-related decompensated cirrhosis, we found baseline MELD score and MVR to entecavir or lamivudine to associate with short- and long-term transplant-free survival. The benefits of an MVR are maintained for up to 10 years even after decompensation, but patients are still at risk for HCC.

Time course of compensatory physiological responses to central hypovolemia in high- and low-tolerant human subjects

Lower body negative pressure (LBNP) simulates hemorrhage in human subjects. Most subjects (67%) exhibited high tolerance (HT) to hypovolemia, while the remainder (33%) had low tolerance (LT). To investigate the mechanisms for decompensation to central hypovolemia in HT and LT subjects, we characterized the time course of total peripheral resistance (TPR), heart rate (HR), and muscle sympathetic nerve activity (MSNA) during LBNP to tolerance determined by the onset of decompensation (presyncope, PS). We hypothesized that 1) maximum (Max) TPR, HR, and MSNA would coincide, and 2) PS would result from simultaneous decreases in TPR, HR, and MSNA in LT and HT subjects but occur earlier in LT than in HT subjects. Max TPR was lower and occurred earlier in LT ( n = 59) than in HT ( n = 113) subjects (LT: 24 ± 1 mmHg·min·1-1 at 756 ± 31 s; HT: 28 ± 1 mmHg·min·1-1 at 1,265 ± 37 s, P < 0.01). Max TPR occurred several minutes before PS. During subsequent decrease in TPR, HR and MSNA continued to increase. Max HR (LT: 111 ± 2 beat/min at 923 ± 27 s; HT: 130 ± 2 beats/min at 1489 ± 23 s, P < 0.01) occurred several seconds before PS. Higher MSNA ( P < 0.01) was attained in HT ( n = 10; 51 ± 5 bursts/min at max TPR; 54 ± 5 bursts/min at max HR) than LT subjects ( n = 4; 41 ± 8 bursts/min at max TPR; 39 ± 8 bursts/min at max HR). The onset of cardiovascular decompensation is a biphasic process in which vasodilation occurs before bradycardia and sympathetic withdrawal. This pattern was similar in LT and HT but occurred earlier in LT subjects. We conclude that sudden bradycardia plays a critical role in the determination of tolerance to central hypovolemia.

The Effect of Passive Heat Stress and Exercise-Induced Dehydration on the Compensatory Reserve During Simulated Hemorrhage

Compensatory reserve represents the proportion of physiological responses engaged to compensate for reductions in central blood volume before the onset of decompensation. We hypothesized that compensatory reserve would be reduced by hyperthermia and exercise-induced dehydration, conditions often encountered on the battlefield. Twenty healthy males volunteered for two separate protocols during which they underwent lower-body negative pressure (LBNP) to hemodynamic decompensation (systolic blood pressure <80 mm Hg). During protocol #1, LBNP was performed following a passive increase in core temperature of ∼1.2°C (HT) or a normothermic time-control period (NT). During protocol #2, LBNP was performed following exercise during which: fluid losses were replaced (hydrated), fluid intake was restricted and exercise ended at the same increase in core temperature as hydrated (isothermic dehydrated), or fluid intake was restricted and exercise duration was the same as hydrated (time-match dehydrated). Compensatory reserve was estimated with the compensatory reserve index (CRI), a machine-learning algorithm that extracts features from continuous photoplethysmograph signals. Prior to LBNP, CRI was reduced by passive heating [NT: 0.87 (SD 0.09) vs. HT: 0.42 (SD 0.19) units, P <0.01] and exercise-induced dehydration [hydrated: 0.67 (SD 0.19) vs. isothermic dehydrated: 0.52 (SD 0.21) vs. time-match dehydrated: 0.47 (SD 0.25) units; P <0.01 vs. hydrated]. During subsequent LBNP, CRI decreased further and its rate of change was similar between conditions. CRI values at decompensation did not differ between conditions. These results suggest that passive heating and exercise-induced dehydration limit the body's physiological reserve to compensate for further reductions in central blood volume.

Course of disease and survival after onset of decompensation in hepatitis B virus-related cirrhosis

Data regarding the outcome of hepatitis B virus (HBV)-related cirrhosis after the onset of decompensation is scanty. From January 1998 to December 2008, a retrospective-prospective inception cohort study involving HBV-related decompensated cirrhotics was performed. Predictors of death and clinical events after the onset of decompensation were evaluated. Patients with co-infection with hepatitis C virus and/or human immunodeficiency virus, alcohol consumption to any degree and diabetes diagnosed before the detection of liver disease were excluded. Two hundred and fifty-three patients (231 males, 139 e-negative), including 102 untreated patients, were analysed. The mean (+/-SD) age was 43.0 (+/-12.0) years. The mean (+/-SD) follow-up period was 47 (+/-47) months. Decompensation was the first presentation of liver disease in 210 (83%) patients. Ascites (70%) and variceal bleed (28%) were predominant modes of decompensation. Forty-three (17%) patients died (22 vs 14% in untreated and treated cohort, respectively; P=0.002). Type 2 hepato-renal syndrome was the commonest cause of death (32%). Survival was independent of e-antigen status. In the total cohorts, predictors of death were occurrence of sepsis with systemic inflammatory response (SIRS), ascites as the initial mode of decompensation, absence of antiviral therapy and events of high-grade hepatic encephalopathy [hazards ratios (HR) of 4.4, 3.6, 2.2 and 1.7 respectively]. In the untreated cohort, initial decompensation with ascites and development of sepsis with SIRS were independent predictors of death (HR 8.5 and 2.3 respectively), while 5-year survival was higher in patients having initial decompensation with variceal bleed vs ascites (29 vs 16%, respectively, P=0.002). Decompensation with ascites and sepsis with SIRS predict reduced survival. Antiviral therapy beyond 6 months improves outcome.

Increased plasma D-lactate is associated with the severity of hemorrhagic/traumatic shock in rats.

D-lactate is produced by indigenous bacteria in the gastrointestinal tract. Mammals do not have the enzyme systems to metabolize D-lactate rapidly. The present study was designed to determine the kinetics of circulating D-lactate levels and to examine whether the severity of shock affects circulating D-lactate levels in rats subjected to hemorrhagic/traumatic shock. Anesthetized rats underwent midline laparotomy (duration 30 min) and were bled to 30-35 mmHg mean arterial pressure (MAP). After the onset of decompensation, MAP was either increased to 40-45 mmHg immediately by administration of Ringer's solution (moderate shock) or after 40% of shed blood volume had been re-infused as Ringer's solution (severe shock). MAP was then maintained at 40-45 mmHg for 40 min by further administration of Ringer's solution (inadequate resuscitation). Subsequently, adequate resuscitation was performed for 60 min with shed blood and additional Ringer's solution. Metabolic acidosis was significantly more pronounced in severe than in moderate hemorrhagic/traumatic shock. Plasma D-lactate levels were already significantly increased at the end of severe hemorrhagic/traumatic shock and remained high during inadequate resuscitation. D-lactate levels were significantly higher after severe than after moderate shock. Endotoxin levels did not correlate with shock severity. Damage to the intestinal mucosa was more profound in severe shock than in moderate shock. Our data suggest that hemorrhagic/traumatic shock is associated with mucosal damage and increased plasma D-lactate levels. The severity of shock affects D-lactate concentrations in plasma. Plasma D-lactate may be a useful marker of intestinal injury after hemorrhagic/traumatic shock.

Hemorrhagic shock induces an S 100 B increase associated with shock severity.

S 100 B is a glial marker of cerebral Injury. In a previous clinical study, we found an S 100 B increase within the first 24 h in patients with multiple trauma and hemorrhagic shock but without cerebral trauma. The aim of our current experimental study was to determine whether this posttraumatic S 100 B increase is caused by extracerebral soft tissue injury or by hemorrhagic shock and whether it is associated with the severity of hemorrhagic shock. Hemorrhagic shock was achieved by bleeding anesthetized rats to a mean arterial pressure (MAP) of 30-35 mmHg through a femoral catheter and maintaining this MAP until incipient decompensation. At incipient decompensation, MAP was either increased immediately to 40-45 mmHg (moderate shock) or was maintained until 40% of shed blood had been returned (severe shock), and then increased to 40-45 mmHg. Resuscitation was provided after 40-45 mmHg MAP had been maintained for 40 min. Soft tissue injury was achieved by midline laparotomy performed at the onset of hemorrhagic shock or without shock and was maintained for 30 min. Hemorrhagic shock caused an early S 100 B increase at the onset of decompensation. S 100 B remained increased for 24 h and was significantly higher after severe than after moderate shock. In contrast, soft tissue injury without hemorrhagic shock caused no S 100 B increase. The data presented demonstrate for the first time that the S 100 B increase is induced by hemorrhagic shock and is associated with the severity of shock.

Survival and Prognostic Indicators in Patients with Hepatitis B Virus–Related Cirrhosis After Onset of Hepatic Decompensation

To determine the 2-year survival and prognostic indicators of hepatitis B virus-related cirrhosis after the onset of hepatic decompensation. Chronic hepatitis B (CHB) patients with cirrhosis and resultant hepatic decompensation have reduced survival. However, the natural history of these patients has not been well characterized in previous studies. Better understanding of survival and prognostic indicators is essential in management of these patients, especially in determining who should be candidates for orthotopic liver transplantation. This is a retrospective longitudinal study of 96 patients with CHB-related cirrhosis after the onset of hepatic decompensation. The overall survival was ascertained, and clinical and laboratory variables were analyzed. Significant prognostic indicators for survival at 2 years were determined using univariate and multivariate analyses with Cox regression model. The overall survival was 80% at 2 years after onset of decompensation. With univariate and multivariate analyses, hepatic encephalopathy and hypoalbuminemia less than 2.8 g/dL were significant prognostic indicators of poor survival probability. The hazard ratios were 5.22 (95% confidence interval, 1.67-16.3) and 8.57 (95% confidence interval, 1.94-37.8), respectively. Patients with hypoalbuminemia less than 2.8 g/dL had a 2-year survival of only 62%. Our study showed that of CHB patients who developed the first episode of hepatic decompensation, those with hepatic encephalopathy or significant hypoalbuminemia or both have worse prognoses. They should be considered potential candidates for liver transplantation.

Glucose infusion arrests the decompensatory phase of hemorrhagic shock.

Waning of hyperglycemia has been shown to be closely associated with the deterioration of mechanisms supporting homeostasis during hemorrhagic shock. However, the mechanisms which link plasma glucose levels to maintenance of homeostasis during hemorrhagic shock are not clear. The goal of the present study was to evaluate the importance of glucose to maintenance of compensatory mechanisms. This was undertaken by maintaining plasma glucose levels through infusion of hypertonic glucose (2-3 M) starting at the onset of decompensation during persisting hypovolemia. Administration of glucose at a rate of between 60 and 80 mumoles/min X kg arrested the fall in glucose concentration and significantly slowed or arrested the decompensatory phase. All of the saline infused control animals (n = 6) died within 3 hours after reaching their maximum shed blood volume, averaging 145 +/- 25 minutes, while two of the eight animals in the glucose infusion group died less than 4 hours after reaching the maximum shed blood volume. The remaining six animals were sacrificed between 270 and 397 minutes (average, 340 +/- 22 minutes) after reaching the maximum shed blood volume since decompensation was arrested. Compared to the saline-infused control group, animals receiving glucose infusion exhibited a more moderate acidosis, and the hemoconcentration which normally accompanies decompensation was also prevented. Since the increase in plasma osmolality and the fraction of the total osmolality change accounted for by glucose was less in the glucose-infused animals, these results suggest that the effect is not mediated through a glucose-related maintenance of a transcapillary osmotic gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart disease in pregnancy.

Pregnancy imposes a significant and predictable circulatory burden which reaches a peak late in the second trimester. Heart failure is the major cause of maternal death in cardiac subjects, and the onset of decompensation and time of death are related to the hemodynamic burden of pregnancy. Supportive care, cardiovascular surgery, and therapeutic abortion are used in managing heart disease complicating pregnancy. Each plays a definite role, and none is a panacea. Pregnancy does not increase the risks of cardiac surgery, and antepartum operations on the heart do not jeopardize the baby. Generally, maternal cardiac disease does not by itself affect the incidence of spontaneous abortion or premature labor, the duration of labor, or the blood loss at delivery. Except in certain specific conditions, heart disease is not an acceptable indication for hysterectomy, hysterotomy, induction of labor, or cesarean section.

A long-term follow-up of operated and medically treated patients with acquired valvular diseases.

A report has been made of the comparison of the clinical results in 448 cases of acquired valvular disease treated surgically or medically. The superiority of the prognosis in patients with mitral stenosis who underwent valvulo-plasty over that in medically treated patients with mitral stenosis or other types of acquired valvular disease was shown in the comparison of survival rates of the patients with same severity of disease according to the NYHA classification at the time of discharge. The better prognosis was also proved by the degree of improvement in cardiac, pulmonary, renal and liver functions etc. The incidence of embolization, which causes no immediate death but makes a patient's life dismal in the majority of cases, has been significantly lower in operated than in medically treated mitral stenosis. But the conclusion as to whether valvuloplasty can prevent recurrence of embolism in patients with previous emboli was reserved in this series because of lack of a sufficient number of the cases. It was statistically indicated that the prognosis is best in operated mitral stenosis with sinus rhythm, next in that with auricular fibrillation, then in medically treated mitral stenosis with sinus rhythm, and worst in that with auricular fibrillation. Many pregnant cardiac patients who developed decompensation during pregnancy continued to be decompensated after delivery, but adequate treatment prevented death for at least one year after the onset of decompensation. No significant differences were noted in duration between onset of the cardiac symptoms and death among groups with different ages of onset. Combined valvular disease was most frequently complicated by subacute bacterial endocarditis, and the prognosis was poor in more than half of the patients with this complication. The authors have considered the pulmonary artery wedge pressure as a reliable and rather easily obtainable index in determining indications for valvuloplasty. It was ascertained again in this series that for the patient with mitral stenosis whose pulmonary artery wedge pressure exceeds 20 mm.Hg valvuloplasty is absolutely indicated. Moreover, it was asserted that the level of the pressure should be lowered to 15 mm.Hg, especially in young patients with mitral stenosis.

Heart Disease in Pregnancy

Pregnancy imposes a significant and predictable circulatory burden which reaches a peak late in the second trimester. Heart failure is the major cause of maternal death in cardiac subjects, and the onset of decompensation and time of death are related to the hemodynamic burden of pregnancy. Supportive care, cardiovascular surgery, and therapeutic abortion are used in managing heart disease complicating pregnancy. Each plays a definite role, and none is a panacea. Pregnancy does not increase the risks of cardiac surgery, and antepartum operations on the heart do not jeopardize the baby. Generally, maternal cardiac disease does not by itself affect the incidence of spontaneous abortion or premature labor, the duration of labor, or the blood loss at delivery. Except in certain specific conditions, heart disease is not an acceptable indication for hysterectomy, hysterotomy, induction of labor, or cesarean section.