Evidence Of Right Ventricular Hypertrophy Research Articles

Molecular signaling pathways in right ventricular impairment of adult patients after tetralogy of Fallot repair.

Right ventricular impairment (RVI) secondary to altered hemodynamics contributes to morbidity and mortality in adult patients after tetralogy of Fallot (TOF) repair. The goal of this study was to describe signaling pathways contributing to right ventricular (RV) remodeling by analyzing over lifetime alterations of RV gene expression in affected patients. RV tissue was collected at the time of cardiac surgery in 13 patients with a diagnosis of TOF. RNA was isolated and whole transcriptome sequencing was performed. Gene profiles were compared between a group of 6 adults with signs of RVI undergoing right ventricle to pulmonary artery conduit surgery and a group of 7 infants, undergoing TOF correction. Definition of RVI in adult patients was based on clinical symptoms, evidence of RV hypertrophy, dilation, dysfunction or elevated pressure on echocardiographic, cardiovascular magnetic resonance, or catheterization evaluation. Median age was 34 years in RVI patients and 5 months in infants. Based on P adjusted value <0.01, RNA sequencing of RV specimens identified a total of 3,010 differentially expressed genes in adult patients with TOF and RVI as compared to infant patients with TOF. Gene Ontology and Kyoto Encyclopedia of Genes databases highlighted pathways involved in cellular metabolism, cell-cell communication, cell cycling and cellular contractility to be dysregulated in adults with corrected TOF and chronic RVI. RV transcriptome profiling in adult patients with RVI after TOF repair allows identification of signaling pathways, contributing to pathologic RV remodeling and helps in the discovery of biomarkers for disease progression and of new therapeutic targets.

Right-ventricular dysfunction in HFpEF is linked to altered cardiomyocyte Ca2+ homeostasis and myofilament sensitivity.

AimsHeart failure with preserved ejection fraction (HFpEF) is frequently (30%) associated with right ventricular (RV) dysfunction, which increases morbidity and mortality in these patients. Yet cellular mechanisms of RV remodelling and RV dysfunction in HFpEF are not well understood. Here, we evaluated RV cardiomyocyte function in a rat model of metabolically induced HFpEF.Methods and resultsHeart failure with preserved ejection fraction‐prone animals (ZSF‐1 obese) and control rats (Wistar Kyoto) were fed a high‐caloric diet for 13 weeks. Haemodynamic characterization by echocardiography and invasive catheterization was performed at 22 and 23 weeks of age, respectively. After sacrifice, organ morphometry, RV histology, isolated RV cardiomyocyte function, and calcium (Ca2+) transients were assessed. ZSF‐1 obese rats showed a HFpEF phenotype with left ventricular (LV) hypertrophy, LV diastolic dysfunction (including increased LV end‐diastolic pressures and E/e′ ratio), and preserved LV ejection fraction. ZSF‐1 obese animals developed RV dilatation (50% increased end‐diastolic area) and mildly impaired RV ejection fraction (42%) with evidence of RV hypertrophy. In isolated RV cardiomyocytes from ZSF‐1 obese rats, cell shortening amplitude was preserved, but cytosolic Ca2+ transient amplitude was reduced. In addition, augmentation of cytosolic Ca2+ release with increased stimulation frequency was lost in ZSF‐1 obese rats. Myofilament sensitivity was increased, while contractile kinetics were largely unaffected in intact isolated RV cardiomyocytes from ZSF‐1 obese rats. Western blot analysis revealed significantly increased phosphorylation of cardiac myosin‐binding protein C (Ser282 cMyBP‐C) but no change in phosphorylation of troponin I (Ser23, 24 TnI) in RV myocardium from ZSF‐1 obese rats.ConclusionsRight ventricular dysfunction in obese ZSF‐1 rats with HFpEF is associated with intrinsic RV cardiomyocyte remodelling including reduced cytosolic Ca2+ amplitudes, loss of frequency‐dependent augmentation of Ca2+ release, and increased myofilament Ca2+ sensitivity.

P308Utility of a prominent R wave in lead V1 of a resting electrocardiogram for detecting significant cardiac pathology in an unselected population of young males

Abstract Background Pre-participation electrocardiogram (ECG) screening is proposed as a means to detect cardiac pathology in asymptomatic individuals, and to select individuals for further cardiac investigation. Isolated ECG finding of Right Ventricular Hypertrophy (RVH) does not require further investigation based on the recent 2017 International Criteria. However, a prominent R wave in V1 has been described in cardiac abnormalities such as Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, cardiomyopathy in Duchenne muscular dystrophy, arrhythmogenic right ventricular cardiomyopathy (ARVC), atrial septal defect and pulmonary hypertension. Purpose We sought to examine the utility of a prominent R wave in V1 as a screening criterion in an asymptomatic young male population of predominantly non-athletes, to detect significant structural cardiac pathology. Methods As part of the Singapore Armed Forces Electrocardiographic and Echocardiographic (SAFE) Protocol Study, pre-military enlistment screening ECG data was collected from 144,346 males between the ages of 16 to 22 from November 2009 to December 2014. Patients with ECGs with a prominent R wave, defined as an R wave ≥0.5mV in lead V1 with an R/S ratio of ≥1, were sent to a tertiary medical facility for a detailed transthoracic echocardiogram and subsequent cardiologist review. Any cardiac pathology identified was deemed significant if it led to the patient being excluded from participation in vigorous physical activity. Results 1,144 patients with an isolated prominent R wave in V1 were studied. The mean age was 18.2±1.09 years and 81% were of Chinese ethnicity. None of the patients had echocardiographic evidence of RVH, 5 patients had a dilated right ventricle and 3 individuals had an elevated pulmonary artery systolic pressure. 11 patients (0.96%) had significant structural heart disease known to be associated with a prominent R wave in V1 that excluded them from participation in physical activity. These included large atrial septal defects (n=8), pulmonary stenosis (n=1), total anomalous pulmonary venous return (n=1) and hypertrophic cardiomyopathy (n=1). The test has a sensitivity of 21.6%, specificity of 93.4%, positive predictive value of 0.96% and negative predictive value of 99.8%, Performance As Screening Criteria Number of Patients With Cardiac Pathology In Those Tested Positive Number of Patients With Cardiac Pathology In Those Tested Negative Positive Predictive Value (%) Negative Predictive Value (%) Sensitivity (%) Specificity (%) 11 40 0.96 99.8 21.6 93.4 Significant Cardiac Pathology Identified Conclusion A prominent R in V1 is not associated with echocardiographic RVH, or ARVC even in a large predominantly non-athletic male population. However, 0.96% of such patients would have other significant cardiac pathologies such as a large atrial septal defect.

A NOVEL MUTATION IN A PATIENT WITH PULMONARY VENO-OCCLUSIVE DISEASE MASQUERADING AS PULMONARY ARTERIAL HYPERTENSION

A NOVEL MUTATION IN A PATIENT WITH PULMONARY VENO-OCCLUSIVE DISEASE MASQUERADING AS PULMONARY ARTERIAL HYPERTENSION

Vein of Galen Aneurysmal Malformation in a Neonate: A Case Report

Vein of Galen aneurysmal malformation (VGAM) is a rare congenital malformation, accounting for less than 1% of cerebrovascular abnormalities. The majority of reported cases have been associated with congestive heart failure (CHF) in the neonatal period. Herein, we present a case of VGAM, diagnosed at 37 weeks of gestation during the intrauterine life Case report: A full-term female newborn presented with severe CHF at two days of age. The patient's peripheral pulses were bounding in all four extremities. The first heart sound appeared to be normal, while the second had an accentuated pulmonic component. A systolic murmur (grade 3/6), best heard in the pulmonary area, was reported, and a cranial bruit was sought and found. The echocardiography showed evidence of right ventricular hypertrophy, while the chest X-ray indicated cardiomegaly with increased pulmonary vascularity. Moreover, echocardiography revealed dilation of the right heart chambers, a patent foramen ovale, severe tricuspid regurgitation, as well as a moderate-sized secundum atrial septal defect and a patent ductus arteriosus with right-to-left shunting. Transcranial ultrasound and contrast-enhanced CT scan of the brain detected a vein of Galen malformation. Magnetic resonance venography confirmed VGAM and identified the vessels feeding the aneurysm. Postnatal management included aggressive medical treatment of CHF. Transarterial embolization of the vessels feeding the aneurysm was suggested. However, the newborn succumbed to her disease on the following day. Conclusion: VGAM, which is a rare cause of cyanosis and heart failure in newborns, can be clinically diagnosed via proper strategies. However, extensive distribution of aneurysm usually precludes surgical management and endovascular treatment.

Survivin role in pulmonary arterial hypertension

Purpose: Survivin is an inhibitor of apoptosis expressed in the vascular lesions of pulmonary arterial hypertension (PAH) and is also involved in myocardial remodeling during left heart failure. The current work aims at: investigating right ventricular (RV) expression of survivin and smac/DIABLO (an inhibitor of survivin) throughout the hemodynamic and morphometric progression of monocrotaline (MCT)-induced PAH; and characterizing the effects of the survivin antagonist terameprocol in pulmonary artery smooth muscle cells (PASMC). Methods: Animal experiments were performed according to the Portuguese law for animal welfare and to the Principles of laboratory animal care (NIH Publication no. 85-23 revised 1985). Adult male Wistar rats received a subcutaneous injection of MCT (60 mg/kg) or equal volume of vehicle. On days 1, 3, 7, 14 and 21 after injection (n=7-12 per group per time-point), RV pressures were measured, heart and lungs were weighted and RV and lung samples were collected for histological analysis. Survivin and smac/DIABLO expression in the RV was determined by immunohistochemistry and western blotting. In a different protocol, a primary culture of PASMC isolated from sham and MCT-treated rats (day 21) was established and the effects of terameprocol in cell proliferation and apoptosis were evaluated by BrdU and TUNEL assays, respectively. Results: RV survivin expression was significantly increased in the MCT groups since day 7, when compared with the SHAM groups. Smac/DIABLO followed an inverse expression pattern with a significant decrease in the MCT groups identified since day 7. This time-point corresponded to the first evidence of RV hypertrophy in MCT-treated rats. Survivin overexpression preceded hemodynamic manifestations of the disease, which started at day 14 with significant increases in RV peak systolic pressure and absolute values of dP/dtmax and dP/dtmin. Terameprocol significantly inhibited proliferation and induced apoptosis of PASMC from sham and pulmonary hypertensive rats in a dose-dependent manner. The pattern of proliferation and apoptosis did not differ significantly between SHAM and MCT groups. Conclusions: Our results demonstrate that survivin upregulation and smac/DIABLO downregulation in the RV precede hemodynamic manifestations of PAH and pair RV hypertrophy, strongly suggesting a role in cardiac remodeling. Pharmacological inhibition of survivin halted cell proliferation and induced apoptosis of PASMC. These findings suggest that targeting survivin in PAH could have dual beneficial effects by reversing pulmonary vascular remodeling and myocardial hypertrophy.

The small heart of the Ornate Tinamou is compatible with endothermy and flight but compromises aerobic metabolism and thermoregulation during recovery from exhaustive activity

Tinamous are an ancient family of neotropical flying birds. Scant data from a few species show that they have a small heart so our aim was to characterize relative heart size of two species of the genus Nothoprocta and assess the physiological limitations associated with a small heart size. Relative heart size (0.24% for the Ornate Tinamou OT, a highland species and 0.28% for the Chilean Tinamou CT, a lowland species) was significantly smaller than high and lowland chickens (0.54% and 0.42% respectively), without evidence of right ventricular hypertrophy. Resting aerobic metabolism was 31% lower in OT than in highland chickens. When subjected to exhaustive activity, OT had elevated glucose and lactate levels suggesting a severe oxygen debt when exhausted. This was further shown as a significant drop in body temperature after an exhaustive bout. Finally heart rate while running on a treadmill at 3 km h−1 was 5% lower in OT, indicating that tinamous cannot compensate for the reduction in heart size with a faster heart rate. Altogether, we provide evidence that heart size is a phylogenetically conserved trait among tinamous and that the Ornate Tinamou cannot compensate aerobically for its small heart. Instead, it relies on anaerobic metabolism incurring in a large oxygen debt while exhausted. Supported by FORMAS Centre of Excellence in Animal Welfare Science and career grant from Linköpings universitet to JA.

Clinical and Electrocardiographic Evaluation of Sickle-Cell Anaemia Patients with Pulmonary Hypertension

Pulmonary hypertension is an emerging complication of sickle cell anaemia with associated increased risk of mortality. In order to evaluate the clinical and electrocardiographic findings in adult sickle-cell patients with pulmonary hypertension, a cross sectional study was conducted on sixty two sickle cell anaemia patients and sixty two age and sex matched normal controls. Elevated pulmonary artery pressures (PAP), defined by PAP ≥ 30 mm Hg on echocardiography, was demonstrated in 41.9% of patients with sickle cell anaemia and in 3.2% of the controls; χ 2 = 26.571, P < 0.001. Right ventricular hypertrophy, increased P-wave duration, QTc interval, and QTc dispersion were significantly associated with pulmonary hypertension. Significant correlation was found between mean PAP and (1) Frequency of crisis (Spearman correlation = 0.320; P = 0.011), (2) body mass index (Pearson's correlation = −0.297; P = 0.019), and (3) QTc interval (Pearson's correlation 0.261; P = 0.040). Pulmonary hypertension in adult sickle anaemia patients is associated with electrocardiographic evidence of right ventricular hypertrophy, and correlates significantly with frequency of vaso-occlusive crisis, and QTc interval. The observations by this study tend to suggest that these parameters could be useful for early detection and prevention of pulmonary hypertension in patients with sickle cell anaemia.

Targeting of c-kit+ haematopoietic progenitor cells prevents hypoxic pulmonary hypertension

Haematopoietic c-kit+ progenitor cells may contribute to pulmonary vascular remodelling and pulmonary hypertension (PH). Stromal derived factor-1 (SDF-1/CXCL12) and its receptors CXCR4 and CXCR7 have been shown to be critical for homing and mobilisation of haematopoietic c-kit+ progenitor cells in the perivascular niche. We administered AMD3100, a CXCR4 antagonist, and CCX771, a CXCR7 antagonist, to chronic hypoxia exposed mice in order to study the role of c-kit+ progenitor cells in PH. CXCL12, CXCR4 and CXCR7 protein expression, haemodynamic parameters, right ventricular mass, extent of vascular remodelling and perivascular progenitor cell accumulation were studied. Chronic hypoxia-exposed mice showed increased total lung tissue expression of CXCR4, CXCR7 and CXCL12 after development of PH. This was associated with significantly increased right ventricular systolic pressure and evidence of right ventricular hypertrophy, vascular remodelling and perivascular c-kit+/sca-1+ progenitor cell accumulation. CCX771 administration did not abrogate these effects. In contrast, administration of AMD3100, whether alone or combined with CCX771, prevented vascular remodelling, PH and perivascular accumulation of c-kit+/sca-1+ progenitor cells, with a synergistic effect of these agents. This study offers important pathophysiological insights into the role of haematopoietic c-kit+ progenitors in hypoxia-induced vascular remodelling and may have therapeutic implications for PH.

Electrocardiography in the Diagnosis of Right Ventricular Hypertrophy in Children

Although the electrocardiogram is commonly obtained in the evaluation of patients with pulmonary hypertension, its value as a screening test for right ventricular hypertrophy or pulmonary hypertension is unclear. Therefore, we sought to determine the value of an electrocardiogram in the diagnosis of right ventricular hypertrophy using echocardiography as the gold standard. We identified children without congenital heart disease who underwent evaluation for suspected pulmonary hypertension that included both an electrocardiogram and echocardiography within a specified time frame. A total of 76 echocardiography-electrocardiogram pairs for pulmonary hypertension were identified. Although there was a significant relationship between electrocardiogram and echocardiography evidence of right ventricular hypertrophy, the sensitivity of an electrocardiogram in diagnosing echocardiography-documented right ventricular hypertrophy was only 69%, and the positive predictive value was 67%. There was no relationship between electrocardiogram changes and Doppler tricuspid regurgitation gradient. Despite a statistically significant relationship between an electrocardiogram and echocardiography in the diagnosis of right ventricular hypertrophy, an electrocardiogram has limited value as a screening tool for right ventricular hypertrophy because of its relatively low sensitivity and positive predictive value.

Presentation of Atrial Septal Defect in the Pediatric Population

Our recent experience indicates that patients with a hemodynamically significant atrial septal defect secundum (ASD2) do not necessarily present with classic physical and electrocardiographic (ECG) findings. The purpose of the study was to review the records of patients either receiving a catheter device or undergoing surgical repair for the closure of ASD2 to determine their initial physical and ECG findings. Therefore, we did a retrospective review of 47 consecutive patients who had echocardiographic evidence of a hemodynamically significant isolated ASD2 and who underwent ASD2 closure. Of these 47 patients, the presenting complaints were murmur (n = 36), chest pain (n = 6), seizure (n = 1), stroke (n = 1), syncope (n = 1), Kawasaki's disease (n = 1), and cardiomegaly (n = 1). Charts were reviewed for the evaluation of four abnormal physical findings: hyperactive right ventricular impulse, split fixed second heart sound, systolic and diastolic flow murmurs; and three ECG abnormalities: right axis deviation, right atrial enlargement, and evidence of right ventricular hypertrophy. In all, 30% of patients had either one or no typical physical findings, 18% had normal ECG findings, and 7% had no physical or ECG findings. On physical examination and ECG, the abnormalities due to ASD2 may be too subtle to detect. Although it is well known that variations can occur in the clinical signs and symptoms typical of ASD2, dependence on classical physical and or ECG findings may result in the underdiagnosis of a significant number of patients.

Ascending aortic origin of a branch pulmonary artery--surgical management and long-term outcome.

Ascending aortic origin of a branch pulmonary artery (AOPA, hemitruncus arteriosus) is a rare congenital malformation. While there have been isolated case reports, larger series, relating to long-term outcomes following surgery are few. This article analyses the surgical results of a series of nine patients, over a period of 29 years. Between 1974 and 2003, nine patients [neonates, 6; infants, 3; male, 5; female, 4] were operated on for AOPA. Median age at presentation was 14 days (range birth to 231 days). Six [corrected] patients (group 1) had associated simple lesions like patent ductus arteriosus or right aortic arch. Three patients (group 2) had complex lesions with right ventricular outflow tract obstruction. One patient (group 2) had DiGeorge syndrome. All patients except group 2 presented with congestive cardiac failure and, in addition one had pre-operative coronary ischemia. Diagnosis was established by angiocardiography in two patients and by echocardiography in seven [corrected] The median age at operation was 28 days (range 7-365). Follow-up period ranged from 7 months to 20.5 years (median 9 years). All nine patients had an anomalous right pulmonary artery (RPA) arising from the proximal ascending aorta, while the left branch was of right ventricular origin. All had evidence of pulmonary hypertension or elevated right ventricular pressure pre-operatively. There was no operative mortality. Of eight patients who had direct anastomosis of the RPA to the main pulmonary artery, one required patch enlargement and another required stenting of an anastomotic stenosis. One patient had a RV-RPA conduit, which required replacement 8, 13, and 14 years later. At follow-up, all patients were alive. All patients in group 1 had normal haemodynamic function and were in NYHA class I. In group 2, all were in NYHA class II with evidence of right ventricular hypertrophy. Four patients had post-operative ventilation-perfusion scans which showed satisfactory perfusion to both lungs. Early surgery is indicated in this lesion and is compatible with good long-term outlook. Surgical repair should not be deferred for corrective procedures of associated cardiac anomalies.

Acute pulmonary edema after percutaneous balloon valvuloplasty for pulmonary valve stenosis

A 66-year-old man was scheduled for percutaneous balloon valvuloplasty of pulmonary valvular stenosis under general anesthesia in the cardiac catheterization laboratory. The patient had a significant history of cardiorespiratory disease. In 1944, his family physician detected a heart murmur, and in 1955, the patient was referred to a cardiologist and told he had “a narrowed valve.” The patient was then lost to follow-up, and his old hospital records were lost. The patient claimed to have been asymptomatic until he sustained an inferior myocardial infarction in 1999 and was referred to this hospital for further investigations. On admission, the patient admitted to smoking 15 cigarettes per day until his myocardial infarction, and his exercise tolerance was reduced to less than 500 meters during the last few years. His medications were aspirin and atenolol. On examination, the patient was noted to be cyanotic, had clubbing of the fingers, had a raised jugular venous pressure, and had bilateral basal crepitations on chest auscultation. The patient had a soft ejection systolic murmur with a normal second heart sound, and there was no right ventricular heave. Further investigations revealed polycythemia (hemoglobin, 19 g/dL; hematocrit, 57.3%), mild renal impairment (serum creatinine, 143 mmol/ L), and arterial blood gases and lung function testing as shown in Tables 1 and 2. A chest radiograph was normal, and a 12-lead electrocardiogram showed T-wave inversion in leads I through III and no evidence of right ventricular hypertrophy. At cardiac catheterization, the patient was found to have moderate left ventricular dysfunction, with a mild stenosis of the left anterior descending coronary artery and complete occlusion of the dominant right coronary artery. There was a severe pulmonary valve stenosis with a peak-to-peak systolic gradient of 90 mmHg (Fig 1). A small atrioseptal defect or patent foramen ovale was noted and confirmed with transesophageal echocardiography. Transesophageal echocardiography did not show any evidence of right or left ventricular dysfunction, and left ventricular ejection fraction was calculated to be 60%. Oxygen saturations and pressure measurements are shown in Tables 3 and 4. It was decided that the pulmonary stenosis should be treated by percutaneous balloon valvuloplasty. Standard anesthetic monitoring was applied, including a 5‐lead electrocardiogram and direct arterial blood pressure measurement via a 20G radial artery catheter inserted under local anesthesia. Pulse oximetry in air showed a saturation (SpO2) of 92%. After preoxygenation (SpO2 increased to 100%), anesthetic induction consisted of fentanyl, 100 g; etomidate, 16 mg; and vecuronium, 8 mg. After endotracheal intubation, the lungs were ventilated with oxygen, air, and isoflurane, 0.8% to 1.4%, for maintenance of anesthesia. The right internal jugular vein was cannulated with 2 long 14G catheters for monitoring of central venous pressure and easy administration of drugs. During the procedure, 1000 mL of lactated Ringer’s solution was infused. Anesthesia was uneventful, and the angiographic findings compared well with the previous measurements. Balloon pulmonary valvotomy using a 25 mm 40 mm balloon resulted in the peak-to-peak gradient falling to 12 mmHg (Figs 2 and 3, Table 5). The patient’s other cardiovascular parameters were unchanged, and PaO2 improved immediately to 9.65 kPa. The procedure time was 15 minutes. The small atrial septal defect was of little or no significance, and no further procedures were carried out. Neuromuscular blockade was reversed with glycopyrrolate, 500 g, and neostigmine, 2.5 mg, and the patient’s lungs were ventilated with oxygen until adequate spontaneous ventilation was restored and the patient’s trachea could be extubated. Total anesthetic time was 45 minutes. The patient was transferred to the postanesthesia care unit to await transfer to the ward. Within 5 minutes of admission to the postanesthesia care unit, the patient developed a tachycardia (120 beats/min), his respiratory rate increased to 30 breaths/min, and SpO2 decreased to 85%, despite supplemental oxygen by facemask.

The DD Genotype of the Angiotensin Converting Enzyme Gene Is Negatively Associated with Right Ventricular Hypertrophy In Male Patients with Chronic Obstructive Pulmonary Disease

The renin angiotensin system plays an important role in the development of pulmonary artery remodeling and right ventricular hypertrophy in hypoxia-induced pulmonary hypertension as may occur in patients with COPD. Several polymorphisms of genes encoding for components of the renin angiotensin system such as the M235T polymorphism in the angiotensinogen gene, the 287-base-pair insertion (I)/deletion (D) polymorphism at intron 16 of the ACE gene, and the A1166C polymorphism in the angiotensin II type 1 receptor gene have been associated with an increased risk of cardiovascular diseases. With respect to the pulmonary circulation, only limited data exist on possible associations between polymorphisms of these genes and pulmonary hypertension and/or right ventricular hypertrophy. The objective of the present study was to investigate a possible relationship between polymorphisms of the renin angiotensin system and electrocardiographic evidence of right ventricular hypertrophy in patients with COPD. We therefore determined the angiotensinogen (M235T), angiotensin converting enzyme (I/D), and angiotensin II type 1 receptor (A1166C) genotypes in 87 patients with severe COPD and correlated these data with electrocardiographic parameters of right ventricular hypertrophy. Thirty-one patients (36%) of 87 patients with COPD showed electrocardiographic evidence of right ventricular hypertrophy. In the male, but not in the female, subgroup, the angiotensin-converting enzyme DD genotype was negatively associated with electrocardiographic evidence of right ventricular hypertrophy (male: chi2 = 3.8, p = 0.05; female: chi2 = 0.05, p = 0.82). We found no associations between the investigated polymorphisms in the angiotensinogen and angiotensin II type 1 receptor genes and electrocardiographic evidence of right ventricular hypertrophy.

ECG observations in Tibetan and Han residents of Lhasa

In order to compare the prevalence of electrocardiographic (ECG) abnormalities suggestive of right ventricular hypertrophy in native and imigrant populations residing at high altitude, a retrospective review was undertaken of data obtained from a random survey of healthy volunteers and persons with chronic mountain sickness (CMS). All persons included in the survey were ambulatory volunteers from the general community who were evaluated at the Tibet Institute of Medical Science in Lhasa, where the elevation is 3,658 meters. The 74 residents of Lhasa, whose ECGs were studied, included 30 healthy Tibetan natives of Lhasa; 24 healthy Han (Chinese) immigrants, born at or near sea level, who had migrated to high altitude as children or adults; and 20 persons with symptoms of CMS. The ECGs of all subjects were reviewed for predetermined criteria suggestive of right ventricular hypertrophy, which were found to be present in 17% of healthy Tibetan natives, 29% of healthy Han immigrants, and 50% of CMS patients. The Han subjects who had migrated as children presented evidence of right ventricular hypertrophy more commonly than did adult imigrants. The overwhelming majority (90%) of persons with CMS were Han. Thus, the frequency of ECG abnormalities consistent with right ventricular hypertrophy was similar in healthy young Tibetan and Han men, but these abnormalities were less common in Tibetan natives than in Han who had migrated to high altitude as children or in CMS patients. The prevalence of ECG evidence of right ventricular hypertrophy increased with duration of high altitude residence among Han.

Long-term Outcome of Cardiac Surgery in Patients With Mitral Stenosis and Severe Pulmonary Hypertension

Pulmonary hypertension increases perioperative risk in patients having mitral valve replacement, but most studies have included patients with mixed mitral valve disease and have not examined long-term outcome. We retrospectively examined the results and predictors of outcome of cardiac surgery in 43 patients (age, 62 +/- 13 years [mean +/- SD]; 81% women) with a primary diagnosis of mitral stenosis and severe pulmonary hypertension (pulmonary artery systolic pressure > or = 60 mm Hg or mean pressure > or = 50 mm Hg). Patients with more than mild mitral regurgitation were excluded. Thirty-eight patients (88%) were in NYHA functional class III or IV, and 11 patients (26%) had an acute presentation requiring urgent surgery. Preoperative hemodynamics demonstrated a mean mitral valve area of 0.7 +/- 0.3 cm2, mean pulmonary artery pressure of 50 +/- 9 mm Hg, and pulmonary artery systolic pressure of 81 +/- 18 mm Hg. Other characteristics included right ventricular failure (18 patients), coronary artery disease (16 patients), and critical aortic stenosis (11 patients). Forty patients underwent mitral valve replacement with St Jude prostheses; 3 had open commissurotomy. Additional surgical procedures included aortic valve replacement (42%), coronary artery bypass graft surgery (26%), and tricuspid valvuloplasty (16%). There were 5 perioperative deaths (11.6%), and 7 other patients (16%) had major complications, including reoperation for hemorrhage, stroke, respiratory failure, myocardial infarction, or a > 30-day hospitalization. Univariate analysis of demographic, hemodynamic, and operative characteristics identified the following predictors of perioperative death (P < .05): acute presentation, clinical evidence of right ventricular failure, impaired left ventricular ejection fraction, and increased left ventricular diastolic pressure. Predictors of complications (P < .05) were acute presentation, ECG evidence of right ventricular hypertrophy, and elevated right ventricular systolic pressure. Multivariate analysis showed only acute presentation and right ventricular hypertrophy as predictors of perioperative death or major complications, respectively. Five- and 10-year actuarial survivals were 80% and 64%, respectively. The only predictor of long-term mortality was advanced age. Functional NYHA status was improved by one grade or more in 76% of survivors. Patients referred to a tertiary care hospital in the United States with mitral stenosis and severe pulmonary hypertension often have other associated cardiac diseases and comorbid conditions. Cardiac surgery can be successfully performed with an acceptable mortality, and risk factors for poor perioperative outcome can be identified by preoperative clinical characteristics. Younger patients have the best long-term survival, and most survivors experienced long-term improvement in functional status.

Clinical Results of Pharyngeal Flap Surgery

Sixty-five patients with cleft palate, with or without cleft lip, who received previous pharyngeal flap surgery for chronic velopharyngeal dysfunction in our department, were examined for velopharyngeal status, speech production patterns, and evidence of nasal airway obstruction. Of the 65 subjects, 54 (83.1 percent) showed velopharyngeal function within normal limits, 43 (66.1 percent) showed normal or near-normal speech production, and 58 (89.2 percent) reported snoring sometimes or often. Of the 58 reporting snoring, electrocardiogram (ECG) data for 33 were examined for evidence of right ventricular hypertrophy. Only one (3 percent) of the 33 showed such possible indication. We conclude that by our methods, pharyngeal flap surgery is an effective treatment for velopharyngeal dysfunction. After surgery, patients may report symptoms of nasal airway obstruction during sleep but are not expected to show ECG changes in cardiac function resulting from oxygen deprivation.

Mechanical Abnormalities in the Rat Ischemic Heart Failure Model Which Lie Downstream to cAMP Production

Objective. We previously showed diminished inotropic responses to isoproterenol in uninfarcted posterior papillary muscles of rats with anterior wall infarcts comprising ⩾30% of the left ventricle. We have also shown that this occurs in the absence of β-receptor downregulation. Our objective was to show a mechanical defect in the rat infarct model which is secondary to cellular defects downstream to cAMP production. Methods. Sprague-Dawley rats were infarcted via coronary ligation. After 3 weeks, the uninfarcted papillary muscle was placed in a muscle bath and exposed to increasing concentrations of dibutyryl cAMP while contracting isometrically at 28°C. Results. The large infarct group showed evidence of right ventricular hypertrophy which was manifested by an increased right ventricular mass. No differences were found in baseline measurements of developed tension (DT); rate of tension development (dT/d t); rate of relaxation (-dT/d t); time to peak tension (TPT); and relaxation time ( t 1/2R). When these muscles were stimulated with dibutyryl cAMP, the large infarct group had a reduced inotropic response as measured by +dT/d t and TPT. No consistent abnormalities were noted in relaxation. The findings are similar to those we noted previously with isoproterenol stimulation. Conclusion. The impaired response to β stimulation in uninfarcted myocardium from rats with large myocardial infarctions is due to cellular defects which lie downstream to cAMP production.

Long-term follow-up of children after repair of atrial septal defects.

It is critical to repair atrial septal defects during childhood to minimize long-term morbidity and mortality. However, only a few studies have examined factors that predict a favorable outcome. To examine prognostic variables in the repair of atrial septal defects. Retrospective analysis of children who underwent repair of atrial septal defects between 1957 and 1981. There were 70 girls and 57 boys with a mean age of 9.3 years at the time of surgery (range 4 months to 20 years). The most common presenting symptoms were fatigue and dyspnea. Before surgery, 74% were in New York Heart Association functional class I, 70% had echocardiographic evidence of right ventricular hypertrophy, and 55% had cardiomegaly on chest radiographs. The average mean pulmonary arterial pressure was 17.1 mm Hg. The only factor significantly related to poor outcome was pulmonary hypertension. Age at surgery did not influence long-term results. Ninety-four percent of patients were in functional class I at follow-up. Repair of atrial septal defects is safe before age 21, but it should be done as early as possible in order to minimize the long-term complications of chronic left-to-right shunting.

Management of typical and dysplastic pulmonic stenosis, uncomplicated or associated with complex intracardiac defects, in juveniles and adults: use of percutaneous balloon pulmonary valvuloplasty with eight-month hemodynamic follow-up.

To alleviate large fixed right ventricular (RV) outflow gradients, percutaneous balloon dilatation of pulmonic stenosis (PS) was performed in 38 patients with mean age of 14 +/- 14 years (median: 9 years, age range: 9 months to 63 years). There were 21 males and 17 females. Thirty-four patients had typical PS (5 of them also having other complex congenital cardiac anomalies, while 13 additional patients had a patent foramen ovale); 2 further subjects had subpulmonic, and 2 dysplastic pulmonary valvular obstructions. Sixteen patients were in the New York Heart Association (NYHA) Class I, 15 in Class II, 6 in Class III, and 1 in Class IV. Electrocardiographic (ECG) evidence of right ventricular hypertrophy (RVH) was present in 29 patients (76%); 3 patients had right bundle branch block (RBBB). For the entire group, there was a marked decrease in the mean systolic transpulmonic gradient in the immediate post-valvuloplasty period (from 97 +/- 43 to 26 +/- 17 mmHg; P < 0.0001). One patient expired 8 hours post-valvuloplasty (he was in the NYHA Class IV, and had severe RV failure). No other cardiovascular complications were encountered; the median hospital stay was 3 days (range: 1-10 days). At an 8-month follow-up, 12 patients who were reevaluated invasively had a median transpulmonic gradient of 27 mmHg (range: 5-92 mmHg) as compared to their pre-valvuloplasty values of 84 mmHg (range: 49-142 mmHg; P < 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)