Progression Of Left Ventricular Hypertrophy Research Articles

405 Impact of insulin resistance on progression of left ventricular hypertrophy in patients with aortic stenosis: A substudy of the astronomer trial

405 Impact of insulin resistance on progression of left ventricular hypertrophy in patients with aortic stenosis: A substudy of the astronomer trial

Vitamin D Receptor Activation and Left Ventricular Hypertrophy in Advanced Kidney Disease

Background: In chronic kidney disease (CKD), left ventricular hypertrophy (LVH) is prevalent and is associated with increased cardiovascular morbidity and mortality. Vitamin D receptor (VDR) activation attenuates LVH progression in animal models. Methods: PRIMO is a multinational, randomized, double-blinded trial with oral paricalcitol in subjects with stages 3–4 CKD, mild-to-moderate LVH and an LV ejection fraction >50%. The primary endpoint is change in the left ventricular mass index (LVMI) compared with placebo after 48 weeks of treatment. The main secondary endpoints are changes in diastolic function parameters. In this paper, we report baseline characteristics from this study. Results: LVMI was 33.0 ± 7.5 g/m^2.7 for males and 30.8 ± 7.2 g/m^2.7 for females (p = 0.04). LVMI correlated with systolic blood pressure (r = 0.24), urine albumin creatinine ratio (r = 0.39), troponin T (r = 0.29), high-sensitivity C-reactive protein (r = 0.25) and plasma levels of B-type brain natriuretic peptide (r = 0.22); all p < 0.01. In multiple linear regression, each remained independently associated with LVMI. The early diastolic velocity of the lateral mitral annulus (E’) was 8.1 ± 2.4 cm/s. E’ was inversely correlated with age in univariate (r = –0.14, p = 0.04) and multivariable (p = 0.02) analysis. Conclusion: Among 227 multinational subjects with stages 3–4 CKD, baseline LVMI correlates with baseline blood pressure, urine albumin creatinine ratio and cardiac biomarkers, and baseline diastolic function correlates with age. This research was funded by Abbott Laboratories; ClinicalTrials.gov No. NCT00497146.

Diagnostics and therapy of left ventricular hypertrophy in haemodialysis patients

Cardiovascular diseases present a leading cause of death in patients treated with haemodialysis. Th e rate of cardiovascular mortality in this population is approximately 9% on an annual basis, with left ventricular hypertrophy, ischemic heart diseases and heart failure having the highest rates of mortality. Left ventricular hypertrophy is present in 75-80 % of haemodialysis-treated patients. Th e most important risk factors for the progression of left ventricular hypertrophy are: hypertension, arteriosclerosis, secondary aortic stenosis, anaemia, increased volume of extracellular fl uid and increased blood fl ow through the vascular access for haemodialysis. Left ventricular hypertrophy is present when the left ventricular mass index on echocardiography exceeds 131 g/m 2 in males and 100 g/m 2 in females. Left ventricular hypertrophy is a risk factor of unfavourable outcome in patients treated with haemodialysis. Th e identifi cation of patients with increased risk of progression of left ventricular hypertrophy, the timely implementation of adequate treatment, and the realisation and maintenance of targeted values of risk factors decelerates the progression of the hypertrophy and leads to the regression of existing left ventricular hypertrophy, the reduction of cardiovascular morbidity and mortality rates and the improvement of the quality of life of patients treated with haemodialysis.

Sequential alterations in Akt, GSK3β, and calcineurin signalling in the mouse left ventricle after thoracic aortic constriction

Left ventricular hypertrophy (LVH) is an adaptive response to chronic biomechanical stress that generally progresses to maladaptive hypertrophy and heart failure (HF). We studied the activation of protein kinase B (Akt/PKB), glycogen synthase kinase 3 beta (GSK3β), and calcineurin (Cn) at 3, 7, 15, 30, and 60 days following transverse aortic constriction (TAC) in 4-week-old mice. Following TAC, GSK3β inactivation at day 3 was associated with Akt activation, whereas at days 15 and 30, it appeared to be controlled by other kinases. Moderate nonsignificant Cn activation occurred at the early stages, and peak activation at day 30, concomitant with GSK3β inactivation and overt LVH and HF. At the latest stage (day 60), despite further progression of LVH and HF, Cn activation appeared attenuated. Early stages of LVH were associated with Ca2+-handling protein upregulation, whereas major Cn activation, associated with GSK3β inactivation, appeared to engage maladaptive hypertrophy and progression to HF associated with Ca2+-handling protein downregulation.

Perhexiline and Hypertrophic Cardiomyopathy

Despite the considerable morbidity and mortality associated with hypertrophic cardiomyopathy (HCM), proven therapeutic modalities for this disorder remain limited. The most feared complication, sudden death, usually due to ventricular tachyarrhythmias, can be averted by the use of implantable defibrillators, but patient selection for such procedures remains problematic. In recent years, evidence has accumulated that the presence of substantial outflow tract obstruction is associated with increased severity of symptoms and increased risk of sudden death,1 and interventions based on amelioration of outflow tract obstruction, via surgical myectomy or alcoholic septal ablation, appear to be relatively effective in improving systematic status.2,3 Article see p 1562 Less clear-cut is the efficacy of various forms of pharmacotherapy. Although there have been a number of reports of symptomatic improvement associated with therapy with β-adrenoceptor antagonists, calcium antagonists, disopyramide, and amiodarone, these studies have not been placebo controlled. Two further concerns are the lack of investigations of pharmacotherapy in patients with nonobstructive HCM, who constitute approximately two thirds of the total group, and the probability that the currently available forms of pharmacotherapy for HCM affect neither the risk of sudden cardiac death4 nor the progression of left ventricular hypertrophy. There is increasing evidence that impairment of myocardial energetics occurs in patients with HCM, and indeed that this impairment is present from the earliest, presymptomatic stages of the disease; much of this information comes from the increasing availability of 31P magnetic resonance spectroscopy to evaluate the ratio of myocardial phosphocreatine to adenosine triphosphate (PCr:ATP).5 Although this technique is currently limited to a substantial extent with regard to determination of energetic status during stress and also imposes substantial limits of spatial resolution within the myocardium, it represents a means to obtain additional insights into the relationships between hemodynamic, autocoidal, and genetic …

E0583 The intervention role of Valsartan on left ventricular hypertrophy and high-sensitivity C-reactive protein i n hypertension patients

ObjectiveTo explore the relationship between high-sensitivity C-reactive protein (hs-CRP) and left ventricular hypertrophy (LVH) and to examine whether angiotensin receptors antagonist ARB could decrease CRP expression, block or invert the...

Pharmacogenetic Interactions Between Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Response to Cibenzoline in Patients With Hypertrophic Obstructive Cardiomyopathy

Cibenzoline, a Class I antiarrhythmic agent, can attenuate the left ventricular pressure gradient (LVPG) in patients with hypertrophic obstructive cardiomyopathy (HOCM). An association between the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene and the progression of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy has been reported. The aim of this study was to investigate the pharmacogenetic interactions between the ACE insertion/deletion polymorphism and the response to cibenzoline in patients with HOCM. Twenty-four patients with HOCM participated in this study. The LVPG and left ventricular function were measured by echocardiography before and 2 hours after administration of a single oral dose of 200 mg cibenzoline. The ACE insertion/deletion polymorphism was genotyped. The frequencies of the genotypes D/D, D/I, and I/I were 16%, 42%, and 42%, respectively. Before administration of cibenzoline, the LVPG was higher in patients with the D allele than in those without it (105 +/- 47 mm Hg versus 64 +/- 24 mm Hg, P = 0.0195). After administration of cibenzoline, the LVPG significantly decreased to 41 +/- 27 mm Hg in those with the D allele (P = 0.0001) and to 33 +/- 24 mm Hg in those without it (P = 0.0003). The LVPG in patients with the D allele was significantly decreased by cibenzoline when compared with patients without the allele (64 +/- 45 mm Hg versus 31 +/- 17 mm Hg, P = 0.038). Patients with HOCM with the ACE D allele had a high LVPG. Cibenzoline was more effective in patients with HOCM with the ACE D allele.

Role of iNOS in Intrinsic Myocyte Dysfunction during Progression of Left Ventricular Hypertrophy

Our objective was to assess the role of inducible nitric oxide synthase (iNOS) in the intrinsic myocyte dysfunction in the compensated and uncompensated stages of left ventricular hypertrophy (LVH). 19 dogs were divided into three groups, Control (CON; n =7), LVH (n=7), and LVH/HF (n= 5), and instrumented for measurements of hemodynamics and LV function. LVH was induced by chronic aortic banding. Progression into LVH/HF was achieved by rapid ventricular pacing. Cardiac myocytes were isolated so that intrinsic contractile function (percent contraction; %C) could be assessed by video imaging. LV systolic pressure and wall stress, and LV wall thickness were increased 2‐fold in LVH compared to CON. LV end‐diastolic pressure was increased 4‐fold and LV dP/dt max was decreased by 30% in LVH compared to LVH/HF. %C was reduced by 30 % in LVH compared CONT (9.4±0.3%). However, in similarity to CON, 1 mM L‐arginine (the substrate for iNOS) caused no change in %C in LVH. Furthermore, expression of iNOS (Western blot) was not increased in LVH relatve to CON. %C was further reduced in LVH/HF. In contrast to LVH, L‐arginine caused marked decrease in %C in LVH/HF, which was blunted by specific iNOS inhibitor AMT. iNOS expression was increased more than 3‐fold in LVH/HF. Taken together, our results suggest that iNOS does not play a role in the intrinsic myocyte dysfunction during compensated LVH, but does so during the uncompensated stage.

Predictors of left ventricular hypertrophy in children on chronic peritoneal dialysis

Conflicting results have been reported in small non-homogenous groups of children with chronic renal failure in terms of casual blood pressure and ambulatory blood pressure monitoring (ABPM) parameters and left ventricular hypertrophy (LVH). The aim of our study was to assess the value of ABPM and hematological and biochemical parameters in predicting LVH in children on chronic peritoneal dialysis (CPD). Echocardiography and 24-h ABPM were performed in addition to routine biochemical and hematological evaluations in 47 children on CPD (26 male, 21 female; mean age 14.74 +/- 3.52 years). Mean daytime systolic blood pressure (SBP) and mean daytime diastolic blood pressure (DBP) values were found to be higher than the mean casual SBP and DBP (p = 0.001) values. Thirty-three (70.2%) children had LVH. The correlations between the left ventricular mass index and ABPM variables were good. Stepwise multiple regression analysis revealed daytime SBP load (beta = 0.652; p < 0.01) and hematocrit (beta = -0.282; p < 0.01) to be independent predictors of LVH. The sensitivity, specificity, positive predictive value, and negative predictive values for the combination of the SBP load >15% and hematocrit value <31% for predicting LVH were 95 [95% confidence interval (CI) 76-99], 78 (95%CI 45-94), 91 (95%CI 73-98), and 88% (95%CI 69-96%), respectively. We conclude that: (1) LVH is prevalent in children on CPD, and (2) a target hematocrit level >31% and daytime SBP load <15% may be preventive for the progression of LVH in the follow-up of children on CPD.

Myocardial effects of VDR activators in renal failure

Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Traditional causes such as diabetes, smoking, aging and hypertension do not fully explain the high rate of morbidity from cardiovascular disease seen in these patients. The renin–angiotensin–aldosterone system (RAAS) regulates extracellular volume homeostasis, which contributes to blood pressure stability. Overactivity of this system is involved in the pathophysiology of cardio-renal disease. New evidence suggests that vitamin D receptor activators (VDRAs) have a suppressive effect on the RAAS; however, VDRAs also have anti-inflammatory and anti-fibrotic effects. We have demonstrated that paricalcitol, a VDRA, ameliorates left ventricular hypertrophy (LVH) in uremic rats by up-regulating the VDR, decreasing myocardial PCNA and also decreasing myocardial oxidative stress. Thus, paricalcitol can suppress the progression of LVH, myocardial and perivascular fibrosis and myocardial arterial vessel thickness presumably by up-regulating the VDR. Paricalcitol may prove to have a substantial beneficial effect on cardiac disease and its outcome in patients with CKD. Prospective randomized studies in CKD patients are necessary to confirm these results.

An Animal Model of Ascending Aortic Stenosis in Rabbits Without Endotracheal Intubation

Experimental animal studies of left ventricular hypertrophy (LVH) usually involve endotracheal intubation, which is associated with a risk of serious tracheal injury and other significant negative sequelae. We developed an animal model of pressure overload hypertrophy caused by constriction of the ascending aorta in rabbits that does not require endotracheal intubation. New Zealand White rabbits of either sex (1.94 +/- 0.12 kg) were randomly assigned to the aortic banding (AB) group (n = 9) and the sham-operated group (n = 8). The sternum was carefully incised along the midline to avoid injury to the parietal pleura. Then, the intervention group underwent AB with three to zero Prolene proximal to the innominate artery without endotracheal intubation. To investigate the effects of the surgical procedure on physiological parameters, echocardiography, histology, and electron microscopy were performed to assess functional and structural hypertrophy at various time intervals. Banding of the ascending aorta created the expected increases in both aortic velocity and the pressure gradient between proximal and distal aorta coarctation. The pressure overload resulted in a robust LVH assessed by transthoracic echocardiography and histology. The animals did not experience severe mechanical ventilatory impairment. We developed a safe, efficient, and reproducible method of producing LVH in rabbits without the need for endotracheal intubation and mechanical ventilation. Ultimately, this model will facilitate focused study of the mechanisms involved with LVH progression.

Acute Elevation of Serum Triglycerides Increases Left Ventricular Contractility Measured by 2D Strain and Strain Rate

Purpose: Elevated serum triglycerides are associated with left ventricular (LV) dysfunction and LV hypertrophy (LVH) in addition to increased aortic stiffness, independent of brachial blood pressure (BP). We sought to establish whether an acute rise in serum triglyceride affects cardiac and vascular function. Methods:On two separate days, 12 healthy males (aged 50± 8 yrs) underwent blinded, randomised infusion of saline or a high-fat supplement solution (Intralipid) to induceanacuteelevationof circulating lipids.Standard2D echocardiography was used to assess LV function (strain, strain rate) and tonometrywas used to record arterial stiffness (aortic pulse wave velocity; PWV) and central BP at baseline and after 1 h infusion of saline or Intralipid. Results: Triglycerides were significantly increased in response to Intralipid, but decreased after saline (Table). Intralipid significantly decreased mean LV end-systolic volume, but did not significantly change aortic stiffness, brachial or central BP. In contrast, both global 2D strain and strain rate decreased significantly (improved) after Intralipid. The lipid-induced change in global 2D strain was significantly correlated with changes in; total cholesterol (r= 0.604), haemoglobin (r= 0.679) and lymphocytes (r= 0.631, P< 0.05 for all). Both age and the change in lymphocyteswere independent predictors of the change in 2D strain (adjusted R2 = 0.69; model P= 0.004). Conclusions: Acute elevation of serum triglycerides increases LV contractility and improves myocardial deformation. Chronic exposure to high circulating lipids may mediate the progression of LVH through augmented cardiac workload resulting from increased blood viscosity or substrate delivery.

Ultrasonic evaluation of the relationship between left ventricular hypertrophy or left ventricular geometry and endothelial function in patients with essential hypertension

Objective To assess the relationship between left ventricular hypertrophy (LVH) or left ventricular geometry (LVG) and endothelial function in patients with essential hypertension (EH). Methods Seventy-six patients and 30 normal subjects were first examined by echocardiography. Brachial artery dilatation induced by reactive hyperemia (DIRH) or nitroglycerin (DING) was detected using high-resolution ultrasonography. Results DIRH was lower in patients with hypertension than in the controls, and the decrease in DIRH was greater in the patients with LVH than that in patients without LVH (4.36±2.54% vs 8.56±1.87 %; P < 0.0001). There were no significant differences in age, serum concentrations of total cholesterol, triglycerides or sugar, blood pressure and the brachial artery dilatation induced by nitroglycerin between the two groups ( P > 0.05). While there was no significant difference in DIRH between the patients with normal left ventricular geometry or cardiac remodeling, the patients showing either eccentric or concentric left ventricular hypertrophy had lower DIRH than the patients with normal left ventricular geometry or cardiac remodeling. The DIRH was the lowest in patients with concentric hypertrophy. Although bivariate analysis showed that the left ventricular mass index (LVMI) correlated well with the brachial artery dilatation induced by reactive hyperemia, diastolic blood pressure and mean blood pressure ( r=-0.61, P < 0.0001; r = 0.27, P < 0.05; r = 0.31, P < 0.05, respectively), a multivariate stepwise regression demonstrated that LVMI correlated only with the brachial artery dilatation induced by reactive hyperemia. Conclusion Left ventricular hypertrophy was related to endothelial dysfunction in essential hypertension. The endothelial dysfunction might be basic and important in the progression of left ventricular hypertrophy.

Anemia en la insuficiencia renal crónica y sus implicaciones cardiovasculares

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Anemia is a common complication of CKD and it is an important independent risk factor for the development and progression of left ventricular hypertrophy (LVH) and heart failure. Anemia is also independently and synergistically associated with an enhanced risk of cardiovascular morbidity and mortality in CKD patients. The availability of erythropoiesis stimulating agents (ESA), such as recombinant human erythropoietin, has greatly improved the management of anemia in CKD patients. By increasing hemoglobin levels, ESA therapy has demonstrated to significantly improve quality of life and decrease morbidity and mortality among these patients. Earlier studies suggested that partial correction of anemia in CKD patients with LVH induced a partial regression of LV mass, while mainly uncontrolled and small-sized studies have suggested that anemia treatment with ESA in CKD patients with congestive heart failure improved NYHA class, cardiac function and reduced hospitalization rates. On the other hand, recent randomized controlled trials have reported no benefit of full anemia correction on LVH and no benefit, or even worse outcomes, in CKD patients versus partial anemia correction. Thus, recent anemia guidelines recommend target haemoglobin levels between 11-12 g/dl in CKD patients receiving ESA.

Erythropoietic stress and anemia in diabetes mellitus

Anemia is one of the world's most common preventable conditions, yet it is often overlooked, especially in people with diabetes mellitus. Diabetes-related chronic hyperglycemia can lead to a hypoxic environment in the renal interstitium, which results in impaired production of erythropoietin by the peritubular fibroblasts and subsequent anemia. Anemia in patients with diabetes mellitus might contribute to the pathogenesis and progression of cardiovascular disease and aggravate diabetic nephropathy and retinopathy. Anemia occurs earlier in patients with diabetic renal disease than in nondiabetic individuals with chronic kidney disease. Although erythropoietin has been used to treat renal anemia for nearly two decades, debate persists over the optimal target hemoglobin level. Most guidelines recommend that hemoglobin levels be maintained between 105g/l and 125g/l. The suggested role of anemia correction--to prevent the progression of left ventricular hypertrophy in patients with diabetes mellitus--is yet to be established. However, an emphasis on regular screening for anemia, alongside that for other diabetes-related complications, might help to delay the progression of vascular complications in these patients.

Author's reply

Thank you for your comments on our work. As you mentioned, it is sometimes difficult to distinguish hypertrophic cardiomyopathy (HCM) from athlete's heart. Delayed gadolinium enhancement (DGE) in cardiac magnetic resonance (CMR) and plasma brain natriuretic peptide (BNP) levels may be useful to detect high risk HCM patients in young athletes. However, changes in these parameters may be smaller in young HCM patients than in our study population (mean age 67.4 years). Moreover, cardiac hypertrophy progresses rapidly in young people, especially in adolescence [[1]Maron B.J. Spirito P. Wesley Y. Arce J. Development and progression of left ventricular hypertrophy in children with hypertrophic cardiomyopathy.N Engl J Med. 1986; 315: 610-614Crossref PubMed Scopus (262) Google Scholar]. A single examination of CMR and/or BNP may not be sensitive enough to exclude high risk HCM in young people. Further studies are necessary to establish the usefulness of DGE in CMR and/or plasma BNP levels for diagnosing HCM in young athletes.

Regression of pressure-induced left ventricular hypertrophy is characterized by a distinct gene expression profile

Left ventricular hypertrophy is a highly prevalent and robust predictor of cardiovascular morbidity and mortality. Existing studies have finely detailed mechanisms involved with its development, yet clinical translation of these findings remains unsatisfactory. We propose an alternative strategy focusing on mechanisms of left ventricular hypertrophy regression rather than its progression and hypothesize that left ventricular hypertrophy regression is associated with a distinct genomic profile. Minimally invasive transverse arch banding and debanding (or their respective sham procedures) were performed in C57Bl6 male mice. Left ventricular hypertrophy was assessed physiologically by means of transthoracic echocardiographic analysis, structurally by means of histology, and molecularly by means of real-time polymerase chain reaction. Mouse hearts were genomically analyzed with Agilent (Santa Clara, Calif) mouse 44k developmental gene chips. Compared with control animals, animals banded for 28 days had a robust hypertrophic response, as determined by means of heart weight/body weight ratio, histologic analysis, echocardiographic analysis, and fetal gene expression. These parameters were reversed within 1 week of debanding. Whole-genome arrays on left ventricular tissue revealed 288 genes differentially expressed during progression, 265 genes differentially expressed with regression, and only 23 genes shared by both processes. Signaling-related expression patterns were more prevalent with regression rather than the structure-related patterns associated with left ventricular hypertrophy progression. In addition, regressed hearts showed comparatively more changes in energy metabolism and protein production. This study demonstrates an effective model for characterizing left ventricular hypertrophy and reveals that regression is genomically distinct from its development. Further examination of these expression profiles will broaden our understanding of left ventricular hypertrophy and provide a novel therapeutic paradigm focused on promoting regression of left ventricular hypertrophy and not just halting its progression.

Expression and tissue localization of β-catenin, α-actinin and chondroitin sulfate proteoglycan 6 is modulated during rat and human left ventricular hypertrophy

Left ventricular hypertrophy (LVH) correlates with chronic renal failure and is one of the most important causes of cardiac mortality. The understanding of the molecular complexity of the disease will help to find biomarkers that open new perspectives about early diagnosis and therapy. This work describes the identification of mediators during pathogenesis relevant for structural remodeling processes of cardiac tissue in uremic LVH. An established rat model of chronic renal failure allowed whole-genome transcriptome analyses as well as the investigation of differential expressed proteins in uremic LVH. The localization of potential biomarkers encoded by candidate genes was done by immunohistochemical analyses of cardiac tissue of the animal model as well as cardiac sections of LVH diseased patients. In addition, the induction of human cardiac fibroblasts (HCF) and human umbilical vein endothelial cells (HUVEC) with the LVH mediator angiotensin II enabled us to investigate uremic LVH progression in vitro. These results point to alterations of myocardial intercellular and cell–matrix contacts in hypertrophic cardiac tissue. Obviously, structural changes of the extracellular matrix are significantly modulated by β-catenin associated signaling pathways. Interestingly, intracellular translocation of β-catenin, α-actinin and chondroitin sulfate proteoglycan 6 (CSPG6/SMC3) was observed in the animal model and in LVH patients. Our results show that the parallel investigation of rat and human cardiac tissue as well as human cellular models in vitro represents a promising strategy to identify reliable biomarkers of LVH.

Substitution of Brown Norway chromosome 16 preserves cardiac function with aging in a salt-sensitive Dahl consomic rat

Determination of the genetic factors that control the progression of left ventricular hypertrophy (LVH) to heart failure has been difficult despite extensive study in animal models. Here we have characterized a consomic rat model of LVH resulting from the introgression of chromosome 16 from the normotensive Brown Norway (BN) rat onto the genetic background of the Dahl salt-sensitive (SS/Mcwi) rat by marker assisted breeding. The SS-16BN/Mcwi consomic rats are normotensive but display LVH equivalent to the hypertensive SS/Mcwi rats at early ages. In this study we tracked the development of LVH by echocardiography and analyzed changes in cardiac function and morphology with aging in the SS-16BN/Mcwi, SS/Mcwi, and BN to determine if the consomic SS-16BN/Mcwi was a model of hypertrophic cardiomyopathy (HCM). Aging SS-16BN/Mcwi rats showed no evidence of heart failure or impaired cardiac function upon extensive analysis of left ventricle function by echocardiography and pressure-volume relationships, while their parental SS/Mcwi experienced deterioration in function between 18 and 36 wk of age. In addition aging SS-16BN/Mcwi did not exhibit tissue remodeling common to pathological hypertrophy and HCM such as increased fibrosis and reduced capillary density in the myocardium. In fact, SS-16BN/Mcwi were better protected from developing LV fibrosis with age than either the hypertensive SS/Mcwi or normotensive BN parental strains. This suggests that a gene or genes on chromosome 16 may be involved with both blood pressure regulation and preservation of cardiac function with aging.

Reoperation after relief of congenital subaortic stenosis☆

We read with interest the paper by Dodge-Khatami et al. [1] on risk factors for reoperation after relief of congenital subaortic stenosis. We compliment them on their extensive statistical analysis and would like to discuss their results as well as our own [2]. Preoperative left ventricular outflow tract (LVOT) gradients in their series ranged from 5 to 120 mmHg, which would lead us to question the need for operation with a preoperative gradient of only 5 mmHg (unless the stenosis was mild or combined with other lesions), their definition of significant postoperative gradients and their threshold for a reoperation. In our experience, and in those of others [3], a peak instantaneous gradient 30 mmHg is considered significant even in the presence of normal left ventricular (LV) function. Progression of LV hypertrophy, LV dysfunction and new aortic incompetence may necessitate operation regardless of the gradient. At a median follow-up of 2.6 years (range 0.3—7.5 years), the authors [1] report a reoperation rate of 19% (n = 11), of which 12 % (5/43) were in the simple group and 40% (6/15) were in the complex group. However, there is no detailed information about patients with immediate postoperative gradients, which may significantly correlate with long-term results [4]. Our experience with discreet subaortic membrane (SAM) consisted of 45 patients with a preoperative gradient of 50— 154 mmHg (86.5 33.2 mmHg); 19 of these had significant LV dysfunction. Transaortic resection of SAM was performed in all patients and was combined with the excision of a wedge shaped segment of septal muscle underlying the membrane. There were no early or late deaths and our follow-up ranged from 18 to 113 months (mean 67 4 months). Only four patients had significant gradients. In all these patients, the immediate postoperative gradients were 25, 20, 25 and 8 mmHg, respectively and progressed to 30—60 mmHg over a 2—5 year period. The actuarial freedom from significant gradients was 89.9 0.4% at 96 months. In one of these, the