COVID-19 in Adults With Congenital Heart Disease.

BACKGROUND: Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. OBJECTIVES: This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. METHODS: Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. RESULTS: From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. CONCLUSIONS: COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity.

Apparent Life-Threatening Events (ALTE): Italian guidelines.

Five years after the first edition, we have revised and updated the guidelines, re-examining the queries and relative recommendations, expanding the issues addressed with the introduction of a new entity, recently proposed by the American Academy of Pediatrics: BRUE, an acronym for Brief Resolved Unexplained Events. In this manuscript we will use the term BRUE only to refer to mild, idiopathic cases rather than simply replace the acronym ALTE per se.In our guidelines the acronym ALTE is used for severe cases that are unexplainable after the first and second level examinations.Although the term ALTE can be used to describe the common symptoms at the onset, whenever the aetiology is ascertained, the final diagnosis may be better specified as seizures, gastroesophageal reflux, infection, arrhythmia, etc. Lastly, we have addressed the emerging problem of the so-called Sudden Unexpected Postnatal Collapse (SUPC), that might be considered as a severe ALTE occurring in the first week of life.

Serum albumin perturbations in cyanotics after cardiac surgery: Patterns and predictions.

INTRODUCTION: Hypoalbuminemia is a well-recognized predictor of general surgical risk and frequently occurs in patients with cyanotic congenital heart disease (CCHD). Moreover, cardiopulmonary bypass (CPB)-induced an inflammatory response, and the overall surgical stress can effect albumin concentration greatly. The objective of his study was to track CPB-induced changes in albumin concentration in patients with CCHD and to determine the effect of hypoalbuminemia on postoperative outcomes. MATERIALS AND METHODS: Prospective observational study conducted in 150 patients, Group 1 ≤18 years (n = 75) and Group 2 >18 years (n = 75) of age. Albumin levels were measured preoperatively (T1), after termination of CPB (T2) and 48 h post-CPB (T3). Primary parameters (mortality, duration of postoperative ventilation, duration of inotropes and duration of Intensive Care Unit [ICU] stay) and secondary parameters (urine output, oliguria, arrhythmias, and hemodynamic parameters) were recorded. RESULTS: The albumin levels in Group 1 at T1, T2, and T3 were 3.8 ± 0.48, 3.2 ± 0.45 and 2.6 ± 0.71 mg/dL; and in Group 2 were 3.7 ± 0.50, 3.2 ± 0.49 and 2.7 ± 0.62 mg/dL respectively. All patients showed a significant decrease in albumin concentration 48 h after surgery (P < 0.01). Analysis between the groups, however, showed no statistical difference. Eleven patients expired during the study period, and nonsurvivors showed significantly lower serum albumin concentration 48 h after surgery 2.3 ± 0.62 mg/dL versus 3.7 ± 0.56 mg/dL in the survivors (P < 0.05). Receiver operating characteristic curve showed that a baseline albumin cut-off value of 3.3 g/dL predicts mortality with a positive predictive value 47.6% and a negative predictive value of 99.2% (P < 0.05). A strong correlation was seen between albumin levels at 48 h with duration of CPB (r2 = 0.6321), ICU stay (r2 = 0.7447) and incidence of oliguria (r2 = 0.8803). CONCLUSIONS: The study demonstrated similar fall in albumin concentration in cyanotic patients (both adult and pediatric) in response to CPB. Low preoperative serum albumin concentrations (<3.3 g/dL) can be used to identify and prognosticate subset of cyanotics predisposed to additional surgical risk.

Red blood cell transfusion decision making in critically ill children.

PURPOSE OF REVIEW: To discuss the tradeoff between permissive anemia and administering red blood cell transfusion to children in pediatric ICUs. RECENT FINDINGS: Postsurgical mortality in adults increases abruptly if their nadir hemoglobin level falls below 5 g/dl. Patients with sepsis, even those in septic shock, and patients with upper gastrointestinal bleeding do not require red blood cell (RBC) transfusion if their hemoglobin level is above 7 g/dl. SUMMARY: Anemia is common in critically ill children and is well tolerated most of the time. RBC transfusion is required in cases of hemorrhagic shock and in children with a hemoglobin level below 5 g/dl. Children with sepsis, including septic shock, those with a severe upper gastrointestinal bleeding and all stable critically ill children, including noncyanotic cardiac children older than 28 days, do not require an RBC transfusion if their hemoglobin level is above 7 g/dl. Transfusion threshold in children with univentricular physiology and in critically ill children with a hemoglobin level between 5 and 7 g/dl remains to be determined.

Percutaneous balloon dilation of severe pulmonary valve stenosis in patients with cyanosis and congestive heart failure.

OBJECTIVES: This article reports outcomes of percutaneous balloon dilation in patients with severe pulmonary valve stenosis, in particular in those treated late with cyanosis, congestive heart failure, and pericardial effusion. BACKGROUND: Percutaneous balloon dilation is the treatment of choice for pulmonary valve stenosis. Although earlier intervention may produce better results, patients may present late with congestive heart failure and cyanosis. METHODS: Fifty-five patients who underwent pulmonary valve balloon dilation, were grouped into two groups, based on the presence or absence of congestive right heart failure and/or central cyanosis. Group I included 33 patients with severe pulmonary valve stenosis, but without clinical evidence of congestive right heart failure in the form of liver enlargement, raised jugular venous pressure, and peripheral edema and/or central cyanosis and group II included 22 patients with severe pulmonary valve stenosis and congestive right heart failure and/or central cyanosis. Their outcomes were compared. RESULTS: Doppler measured transvalvar pressure gradient decreased from 110.2 ± 34.0 mm Hg before to 52.5 ± 28.7 mm Hg in group I after dilation (P < 0.001), and from 138.4 ± 32.3 mm Hg to 53.9 ± 19.3 mm Hg in group II, (P < 0.001). Complications included ventricular tachycardia/fibrillation in three patients and severe bradycardia in one patient in group II. Twelve patients in group II developed clinical and radiologic evidence of reperfusion injury/pulmonary edema within the first 24 hr of intervention and needed ventilation for 2-9 days. Three of these patients died from intractable pulmonary edema. On follow up, clinical and echocardiographic improvement parameters were similar in the two groups. CONCLUSION: Those patients with severe pulmonary valve stenosis with congestive right heart failure, especially those with pericardial effusion, ascites and cyanosis, represent an important technical and clinical challenge. They are a high-risk group with or without treatment. If they survive the procedure, they may still remain at a high risk in the first few days afterward. Maintaining their ventilator and inotropic support after balloon dilation may increase survival. However, excellent results can be obtained.

Cyanotic nephropathy--a morphometric analysis.

OBJECTIVE: Nephropathy is a known complication in cyanotic congenital heart disease (CCHD). This study was undertaken for an objective analysis of histopathological changes of cyanotic nephropathy at autopsy. DESIGN: Retrospective case records studied. SETTING: Tertiary care teaching hospital affiliated to medical college in Mumbai, India. PATIENTS AND METHODS: The renal histopathological findings of 50 consecutive autopsies in patients with CCHD were compared with 25 age-matched controls. The Bowman's capsular, glomerular tuft, and hilar arteriolar diameters were measured morphometrically. Statistical analysis was performed using unpaired t-test. A P value equal to or less than .05 was considered significant. RESULTS: Among the 50 autopsied cases of CCHD, there were 35 males and 15 females, with a mean age of 4.64 years. The renal changes observed were glomerulomegaly, glomerulosclerosis, periglomerular fibrosis, hyperplastic arteriolosclerosis, and interstitial fibrosis. The objectively measured parameters were higher in cases as compared with controls in all age groups, and further these were also found to be higher in patients having decreased pulmonary arterial blood flow than those having normal to increased pulmonary arterial blood flow. The difference in Bowman's capsular and glomerular tuft diameters was statistically significant in the neonates and children in the age groups, 1-5 years and above 10 years. The difference in hilar arteriolar diameter was statistically significant for all age groups except neonates. CONCLUSION: Patients with CCHD show significant changes in the kidneys as assessed morphometrically, leading to renal dysfunction, and the age of the patients plays a role in their development.

Axillary arteriovenous fistula for the palliation of complex cyanotic congenital heart disease: is it an effective tool?

OBJECTIVE: Patients with complex cyanotic congenital heart disease and a bidirectional cavopulmonary connection who are not candidates for or had failed Fontan operation may experience progressive cyanosis. An axillary arteriovenous anastomosis may be constructed to augment pulmonary blood flow. This report reviews our results with this approach in this complex group of patients. METHODS: The records of patients with previous cavopulmonary connections who underwent a surgical anastomosis between the axillary artery and the vein for palliation of severe progressive cyanosis were reviewed. RESULTS: Eleven patients were identified. The median age at the time of the axillary arteriovenous anastomosis was 19.2 years (7.97-41.75 years). Seven patients were not candidates for the Fontan operation, and 4 patients had failed Fontan surgery. Three of the anastomoses were constructed with a side-to-side technique, and 8 anastomoses were constructed with a short interposition graft. Median fistula size was 5 mm (3-6 mm). There was no operative mortality and 1 late death. Median survival was 2.85 years (0.01-7.22 years). All fistulae were patent at follow-up. Median preoperative arterial oxygen saturation was 84% (80%-86%) and 82% (76%-88%) at follow-up (P = .38). Median preoperative hemoglobin was 18.5 g/dL (11.7-22.6 g/dL) and 19.2 g/dL (14.6-22.6 g/dL) at follow-up (P = .97). Median preoperative systemic ventricular ejection fraction was 51% (27%-60%) and 46.5% (28%-60%) at follow-up (P = 1). Significant functional improvement was seen in only 1 patient. CONCLUSIONS: In patients with complex cyanotic congenital heart disease who are not candidates for or had failed Fontan operation, palliation with an axillary arteriovenous fistula did not improve cyanosis or polycythemia. Functional outcome and ventricular ejection fraction did not improve or deteriorate.

Developing and optimizing a chronic cyanotic swine model.

BACKGROUND: Pulmonary artery (PA)-left atrial (LA) shunt models in piglets have been described, but technical details critical to limit morbidity/mortality and promote study of chronic cyanosis are lacking. Accordingly, we describe our experience with an optimized technique. MATERIALS AND METHODS: In 25 6- to 8-wk-old Yorkshire piglets, a beveled, 8 mm, polytetrafluoroethylene tube graft was anastomosed to the PA and LA. Systemic pressure was maintained at >60 mmHg. Saturation targets were met by adjusting a Teflon band on the graft and distal PA. The target oxygen saturation (SO(2)) was 85% on a 50% fraction of inspired oxygen (FiO(2)). If the SO(2) was <75% on a 50% FiO(2), the graft was constricted to achieve a SO(2) ≥ 90% on a 100% FiO(2) and 75%-80% on a 21% FiO(2). Complications affecting mortality were neutralized with a stepwise strategy to minimize risk. RESULTS: Thrombosis, blood loss, and arrhythmia were determinants of survival. Protocol optimization over time increased survival while assuring chronic cyanosis. Survival approached 90%, with a SO(2) of 80% to 90%, 3 to 5 wk postoperatively. Complications included bleeding, excessive hypoxemia, uncontrolled shunt flow, arrhythmias, and thrombosis. CONCLUSIONS: Refinement of surgical technique, shunt adjustment via graft banding, and thrombotic and arrhythmia prophylaxis are the keys to success with this model.

Predictors of mortality in adult patients with congenital heart disease.

BACKGROUND: Most patients with congenital heart disease (CHD) reach adulthood thanks to the successful efforts of cardiac surgeons. However, sudden cardiac deaths are significantly more prevalent in this population, and survival is reduced when compared to the general population. The aim of this study is to define the prognostic value of selected clinical parameters to predict mortality in adult CHD patients referred to the specialist outpatient centre. The following parameters were analyzed as potential predictors of long-term survival: complexity of heart defect, past surgical intervention, heart failure (functional class according to NYHA > I), cyanosis, age and gender. METHODS: We analyzed data gathered from 1,304 patients (568 male) aged 18 to 72 (mean 29.4 +/- 10.6) between 1995 and 2004. Mean duration of follow-up was 3.52 +/- 1.83 years. RESULTS: During follow-up, 29 deaths were recorded (2.2%). Higher mortality was found in the group of patients with complex as oppposed to simple CHD (28 [6.7%] vs. 1 [0.1%]; p = 0.00001), in subjects without surgical correction as opposed to those operated on (21 [6.1%] vs. 8 [0.8%], p = 0.00001). General survival was 99.1% at two years and 96.6% at five years. In univariate survival analysis, all single clinical variables except patient gender were associated with increased risk of death (p = 0.00001 for all). All patients who died presented with heart failure. In multivariate analysis, the independent predictor of mortality was cyanosis (heart rate 38.1). Complexity of lesion (heart rate 6.4) represented a relative risk factor. CONCLUSIONS: Heart failure and cyanosis are negative predictors of survival in adult patients with CHD. Complexity of the lesion increases the relative risk of mortality. Past cardiac surgery is associated with better survival, but, as with age and gender, it is not a significant prognostic factor.

Neonatal Blalock-Taussig shunt: technical aspects and postoperative management.

A systemic-pulmonary artery shunt in neonates with decreased pulmonary blood flow is technically demanding. We describe our surgical technique, postoperative management, and results in 19 neonates who underwent a modified Blalock-Taussig shunt between April 2003 and March 2006. Prostaglandin infusion was required in 8 patients who were critically cyanosed, and 5 were on inotropic support preoperatively. A 3.5 or 4.0-mm polytetrafluoroethylene graft was anastomosed with 8/0 polypropylene suture. Postoperatively, systemic pressure was kept slightly higher than normal, and heparin was started early. One patient required revision of the shunt, and one was reexplored for bleeding. There were 2 hospital deaths (mortality, 11%) in patients with preoperative hemodynamic instability. The mean follow-up period was 12 months, with no late postoperative shunt blockage or death. Meticulous surgical technique and judicious use of heparin and inotropic agents improved the outcome and reduced the incidence of shunt blockage and reexploration for bleeding.

Predictive factors for long-term prognosis in adults with cyanotic congenital heart disease--Japanese multi-center study.

OBJECTIVE: Adults with cyanotic congenital heart disease (CCHD) are associated with a significant incidence of morbid events and premature deaths that may be predicted during childhood. We aimed to identify predictive factors related to long-term prognosis through a Japanese multi-center cross-sectional study. METHODS: Data were collected from 253 adults with CCHD (126 men; age 28 (18 to 56) years) from 15 participating centers between 1998 and 2003. Laboratory data such as cardiothoracic ratio (CTR), percutaneous oxygen saturation (SpO2), hematocrit levels (Ht) and platelet counts (Pl-c) at the age of 15 years were collected for predictive factor analysis for death and cardiovascular and systematic events. Predictive factors were determined by multivariate Cox regression analysis. RESULTS: After a mean follow-up of 21 (0-42) years, 23 patients died with a median age of 29 (18-54) years (heart failure in 8, sudden in 6 and systematic complications in 9). Survival since 18 years of age was 91% and 84% at 10 and 20 years, respectively. Significant predictive factor for death was Pl-c<130x10(9)/l and for renal failure (n=7) was Ht>65%. 162 patients were hospitalized and predictors for hospitalization due to heart failure (n=45) were common atrioventricular canal CTR>60% and Pl-c<100x10(9)/l and that due to arrhythmias (n=44) were systematic right ventricle and CTR>60%. CONCLUSIONS: This multi-center study provides an objective basis of assessing the long-term prognosis in patients with CCHD. These data are useful in making decisions regarding medical management and in favorably altering the non-operative course of the disease.

Are cyanosed adults with congenital cardiac malformations depressed?

OBJECTIVE: To assess the incidence of depression, and the ability to interact socially, in adult patients with chronic cyanosis and congenital cardiac malformations. DESIGN: Prospective study of consecutive patients. SETTING: Single institution, tertiary referral centre. PATIENTS: Between 1993 and 2000, we assessed 76 patients with congenital cardiac malformations and persistent cyanosis, having a median age of 36.5 years, with a range from 19 to 64 years, at the time of referral. Female patients accounted for just under half (48.6%) of the sample. Just under two-fifths of the cohort (39.5%) had functionally univentricular cardiac anatomy, while 14.8% had tetralogy of Fallot with pulmonary atresia and aorto-pulmonary collateral arteries, and 17% had the Eisenmenger syndrome. During the period of follow-up, 17 (22.4%) of the patients died. ASSESSMENT: We used clinical interviews and non-invasive assessment, employing Zung's questionnaire which provides a scale for the self-rating of depression. On this scale, a score above 50 points is indicative of depression. RESULTS: Of the survivors, 32 (54%) completed the self-rating questionnaires. Of these, 20 responders (63%) considered that they lead full lives, including sexual activities, while 26 (81%) had never harboured suicidal thoughts. Depression was diagnosed in 11 responders (34%), with a mean score of 66.9, standard deviation of 8.7, and a range from 53 to 89. The remaining 21 patients (66%) were without signs of depression, scoring a mean of 41.5, with standard deviation of 5.5, and a range from 35 to 46. Depression was associated with older age (40.5 years versus 33.5 years, p = 0.01), worse functional state in the classification of the New York Heart Association (2.95 versus 2.48, p = 0.03), and unemployment (p < 0.0001), but independent from the severity of cyanosis, the level of the haematocrit, the saturation of oxygen, or previous surgical treatment. CONCLUSIONS: To our knowledge, this is the first evidence suggesting a relatively high incidence of depression in adults with congenital cardiac malformations and persistent cyanosis. Larger, multi-centric studies will be needed to confirm or refute these findings.

Retinol is specifically required during midgestation for neonatal survival.

Previous work has demonstrated that vitamin A-deficient, retinoic acid-supplemented pregnant rats cannot complete gestation without the administration of retinol. As little as 2 micrograms administered on day 10 of gestation is sufficient to prevent the characteristic fetal resorption that begins at day 15 of gestation. This single dose of retinol supports continued development through day 20 of gestation. However, if gestation is allowed to proceed to parturition, the newborn pups die within a few minutes of being severed from the umbilical cord. The pups are born with a pink and healthy skin tone, but within seconds of umbilical separation, they begin to gasp for air, become cyanotic in appearance, and die within several minutes from an apparent inability to obtain oxygen. Histological examination of these neonates demonstrates delayed pulmonary development. Branching and scalloping of ducts and saccule and subsaccule formation are decreased. This phenotype is consistent with that observed in respiratory distress syndrome seen in some premature human infants.

Clinical experience in poisonings following exposure to blasticidin S, a curiously strong fungicide.

The fungicide blasticidin S has been used against a rice blast disease. Reports on its human toxicity are extremely limited, and irritation to GI tract, eye and skin are the presenting symptoms in most afflicted cases. Fatalities resulting from profuse intestinal fluid loss with subsequent hypotension have also been recorded. In an attempt to delineate the clinical pictures of blasticidin S poisoning, a retrospective study covering an 8.5-y period was then conducted. A total of 28 blasticidin S poisoning exposures, including 24 suicidal ingestions, were recorded. The ingested amounts in most cases were rather large, while 2 cases were found with estimated dosages up to 10 g. The presented symptoms in most cases were immediate vomiting, abdominal pain, diarrhea and sore throat which were resolved after conservative treatment. Nevertheless, hypotension, arrhythmia, acrocyanosis, aspiration, and even coma occurred in severe cases. Fatalities were noted in 5 patients, in whom profound hypotension and severe aspiration pneumonitis were the main features. Poisoning following blasticidin S ingestion remains a challenge to acute health care physicians. Adequate administration of i.v. fluid and careful monitoring of electrolytes have been considered as the mainstay in the treatment of blasticidin S poisoning. Prevention of aspiration and ventilatory support are also crucial for life-saving since poisoning cases might succumb after massive aspiration.

Blue breath holding is benign.

In their recent publication in this journal, Southall et al described typical cyanotic breath holding spells, both in otherwise healthy children and in those with brainstem lesions and other malformations. Their suggestions regarding possible autonomic disturbances may require further study, but they have adduced no scientific evidence to contradict the accepted view that in the intact child blue breath holding spells are benign. Those families in which an infant suffers an 'apparently life threatening event' deserve immense understanding and help, and it behoves investigators to exercise extreme care and self criticism in the presentation of new knowledge which may bear upon their management and their morale.

Respiratory failure due to choriocarcinoma: a study of 103 dyspneic patients.

Treatment of choriocarcinoma is mostly successful but there is still appreciable mortality from early respiratory failure. A series of 135 patients with choriocarcinoma presenting with dyspnea between 1960 and 1988 was studied to find prognostic factors for early respiratory death and to identify how mortality may be further reduced. Mortality with respect to early respiratory death (ERD) was 11% and was significantly associated with WHO prognostic score, chest X-ray appearance, central cyanosis, tachycardia, anemia, and clinical evidence of pulmonary hypertension. Indicators on chest X ray of high risk of ERD were the presence of more than 10 opacities, extensive opacification of lung fields, size of metastases, and hazy background obscuring the vascular pattern. Intensity of initial treatment was not correlated with this outcome. A set of criteria has been derived which will predict ERD with 100% sensitivity and 38% positive predictive value. These are opacification of lung fields on chest X ray of more than 50%, OR initial plasma hCG level greater than 10(5) when there is anemia and a history of chest pain. Patients presenting with choriocarcinoma and dyspnea who fulfill these criteria should be considered for extracorporeal perfusion techniques. As respiratory failure in this condition is characterized by hypoxemia and right-to-left shunting, extracorporeal perfusion should be effective. Ventilation should be avoided as no patient survived mechanical ventilation.

Bidirectional cavopulmonary shunts: clinical applications as staged or definitive palliation.

A standard Glenn anastomosis between the superior vena cava and the right pulmonary artery has been the accepted mode of treatment for patients with complex cyanotic congenital heart disease. We report our experience in 18 patients with such disease who underwent a bidirectional cavopulmonary shunt because of increasing cyanosis and growth cessation. All patients were considered less than "ideal" candidates for a Fontan procedure. We divided the patients into two groups: group 1 had azygos continuation and group 2 did not. Fourteen patients required hypothermic cardiopulmonary bypass. Bidirectional pulmonary blood flow was achieved in all patients. Only 1 death occurred (group 2). The improvement in oxygen saturation and overall clinical condition of these patients, together with the low mortality and morbidity, is encouraging. However, long-term follow-up is mandatory for a comprehensive evaluation of this surgical approach as definitive palliation or as a first stage for a Fontan operation.