Development Of Left Ventricular Dilatation Research Articles

Regulation and impact of cardiac lymphangiogenesis in pressure-overload-induced heart failure

Lymphatics are essential for cardiac health, and insufficient lymphatic expansion (lymphangiogenesis) contributes to development of heart failure (HF) after myocardial infarction. However, the regulation and impact of lymphatics in non-ischemic cardiomyopathy induced by pressure-overload remains to be determined. Investigate cardiac lymphangiogenesis following transverse aortic constriction (TAC) in adult male or female C57Bl/6J or Balb/c mice, and in patients with end-stage HF. Cardiac function was evaluated by echocardiography, and cardiac hypertrophy, lymphatics, inflammation, edema, and fibrosis by immunohistochemistry, flow cytometry, microgravimetry, and gene expression analysis, respectively. Treatment with neutralizing anti-VEGFR3 antibodies was applied to inhibit cardiac lymphangiogenesis in mice. The gender- and strain-dependent mouse cardiac hypertrophic response to TAC, especially increased ventricular wall stress, led to lymphatic expansion in the heart. Our experimental findings that ventricular dilation triggered cardiac lymphangiogenesis was mirrored by observations in clinical HF samples, with increased lymphatic density found in patients with dilated cardiomyopathy. Surprisingly, the striking lymphangiogenesis observed post-TAC in Balb/c mice, linked to increased cardiac Vegfc, did not suffice to resolve myocardial edema, and animals progressed to dilated cardiomyopathy and HF. Conversely, selective inhibition of the essentially Vegfd-driven capillary lymphangiogenesis observed post-TAC in male C57Bl/6J mice did not significantly aggravate cardiac edema. However, cardiac immune cell levels were increased, notably myeloid cells at 3 weeks and T lymphocytes at 8 weeks. Moreover, while the TAC-triggered development of interstitial cardiac fibrosis was unaffected by anti-VEGFR3, inhibition of lymphangiogenesis increased perivascular fibrosis and accelerated the development of left ventricular dilation and cardiac dysfunction ( Fig. 1 ). We demonstrate for the first time that endogenous cardiac lymphangiogenesis limits pressure-overload-induced cardiac inflammation and perivascular fibrosis, thus delaying HF development. While these findings remain to be confirmed in a larger study of HF patients, we propose that under settings of pressure-overload poor cardiac lymphangiogenesis may accelerate HF development.

Factors Associated with Echocardiographic Abnormalities in Patients with Chronic Kidney Disease in a Tertiary Hospital in Ivory Coast

Background: Cardiovascular risk factors (CVRF) are very frequent in pa-tients with chronic kidney disease (CKD) and impose a new environment to which the heart must adapt. Cardiac ultrasound is a non-invasive and easy-to-perform examination that allows quantitative and qualitative assessment of the anatomy and function of the heart. The objectives of this study were to describe abnormalities observed on trans-thoracic Doppler-echocar-diography and to investigate the factors associated with them. Materials and Method: This was a monocentric retrospective cross-sectional study conducted in CKD patients hospitalized in a hospital center in Côte d'Ivoire from January 2017 to December 2018. Results: One hundred and four cases were collected with a mean age of 48.87 ± 14.47 years and a sex ratio of 1.7. Patients with end-stage-renal-disease (ESRD) represented 83.7% with 55.8% of cases of chronic glomerulonephritis. Cardiovascular risk factors were 100% anemia, 84.6% inflammatory profile, 77.9% hypertension, 76.9% hypocalcemia and in 67.3% oedema. Cardiac abnormalities were observed in 78.8% of patients. Left ventricular hypertrophy (LVH), accounting for 20.2% of cases, was associated with male gender (OR 0.127 CI 0.025 - 0.643; p = 0.013) and hypertensive nephropathy (OR 0.189 CI 0.056 - 0.637; p = 0.007). History of hypertension (OR 0.297 CI 0.084 - 1.050; p = 0.060) and diabetes (OR 5.315 CI 1.260 - 22.419; p = 0.023), hypertensive nephropathy (OR 0.174 CI 0.052 - 0.585; p = 0.005) and hypocalcemia (OR 6.094 CI 1.723 - 21.559; p = 0.005) are incriminated in the development of left ventricular dilatation (LVD) which accounted for 38.5% of cases. Conclusion: Left ventricular hypertrophy and dilatation are the main echocardiographic abnormalities observed in our population.

Administration of a TLR9 Inhibitor Attenuates the Development and Progression of Heart Failure in Mice

Mitochondrial deoxyribonucleic acid, containing the unmethylated cytidine-phosphate-guanosine motif, stimulates Toll-like receptor 9 to induce inflammation and heart failure. A small chemical, E6446 [(6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole)], is a specific Toll-like receptor 9 inhibitor in cardiomyocytes. In this study, we showed that E6446 exerts beneficial effects for the prevention and treatment of pressure overload-induced heart failure in mice. When administered before the operation andchronically thereafter, E6446 prevented the development of left ventricular dilatation as well as cardiac dysfunction, fibrosis, and inflammation. Furthermore, when administered after the manifestation of cardiac dysfunction, E6446 slowed progression of cardiac remodeling. Thus, the inhibitor may be a novel therapeutic agent for treating patients with heart failure.

Frequent Premature Ventricular Contractions: An Electrical Link to Cardiomyopathy.

Heart failure is common and is associated with significant morbidity and mortality. Identifying potentially modifiable risk factors for the development of ventricular dysfunction is important in both the prevention and the treatment of this condition. Arrhythmia disorders are increasingly recognized as contributory to the development of ventricular failure. Poorly controlled supraventricular tachyarrhythmias, altered left ventricular activation due to left bundle branch block or right ventricular pacing, and frequent premature ventricular contractions (PVCs) constitute the main subtypes of arrhythmia disorders that are associated with the development of ventricular dysfunction. PVCs are common and are considered benign in the absence of structural heart disease. Frequent PVCs, defined as greater than 20% of all QRS complexes on standard 24-hour Holter monitoring, are associated with the presence or subsequent development of left ventricular dilatation and dysfunction. Catheter ablation of frequent PVCs has been demonstrated to be effective at PVC suppression and is associated with improvement or normalization of ventricular function; thus defining a specific, reversible form of ventricular dysfunction termed PVC cardiomyopathy. In patients presenting with high burden PVCs, an assessment for symptoms and associated cardiomyopathy is warranted and, in the appropriate clinical setting, PVC catheter ablation may be a reasonable treatment option.

Echocardiographic Datasets Showing Development of Cardiac Remodelling in Rats at Different Time-points after Acute Myocardial Infarction

A B S T R A C T The simulation of the time course of development of heart failure after an acute myocardial infarction requires large, open-access datasets. In this report, we present large echocardiographic datasets of cardiac function in rats after myocardial infarction at two different time points (2 and 13 weeks). We present measurements that show the deterioration of global left ventricular (LV) function, regional function, development of LV dilation, reactive hypertrophy and changes in LV geometry. We present in addition measurements showing the degree of cardiac injury assessed by the area and weight of the scar tissue. These data represent the progressive nature of cardiac remodelling and could be used to build computational models to predict the development of heart function deterioration based on the extent of myocardial injury and the development of LV remodelling.

Permanent ligation of the left anterior descending coronary artery in mice: a model of post-myocardial infarction remodelling and heart failure.

Heart failure is a syndrome in which the heart fails to pump blood at a rate commensurate with cellular oxygen requirements at rest or during stress. It is characterized by fluid retention, shortness of breath, and fatigue, in particular on exertion. Heart failure is a growing public health problem, the leading cause of hospitalization, and a major cause of mortality. Ischemic heart disease is the main cause of heart failure. Ventricular remodelling refers to changes in structure, size, and shape of the left ventricle. This architectural remodelling of the left ventricle is induced by injury (e.g., myocardial infarction), by pressure overload (e.g., systemic arterial hypertension or aortic stenosis), or by volume overload. Since ventricular remodelling affects wall stress, it has a profound impact on cardiac function and on the development of heart failure. A model of permanent ligation of the left anterior descending coronary artery in mice is used to investigate ventricular remodelling and cardiac function post-myocardial infarction. This model is fundamentally different in terms of objectives and pathophysiological relevance compared to the model of transient ligation of the left anterior descending coronary artery. In this latter model of ischemia/reperfusion injury, the initial extent of the infarct may be modulated by factors that affect myocardial salvage following reperfusion. In contrast, the infarct area at 24 hr after permanent ligation of the left anterior descending coronary artery is fixed. Cardiac function in this model will be affected by 1) the process of infarct expansion, infarct healing, and scar formation; and 2) the concomitant development of left ventricular dilatation, cardiac hypertrophy, and ventricular remodelling. Besides the model of permanent ligation of the left anterior descending coronary artery, the technique of invasive hemodynamic measurements in mice is presented in detail.

Distinct Effects of Leukocyte and Cardiac Phosphoinositide 3-Kinase γ Activity in Pressure Overload–Induced Cardiac Failure

Signaling from phosphoinositide 3-kinase γ (PI3Kγ) is crucial for leukocyte recruitment and inflammation but also contributes to cardiac maladaptive remodeling. To better understand the translational potential of these findings, this study investigates the role of PI3Kγ activity in pressure overload-induced heart failure, addressing the distinct contributions of bone marrow-derived and cardiac cells. After transverse aortic constriction, mice knock-in for a catalytically inactive PI3Kγ (PI3Kγ KD) showed reduced fibrosis and normalized cardiac function up to 16 weeks. Accordingly, treatment with a selective PI3Kγ inhibitor prevented transverse aortic constriction-induced fibrosis. To define the cell types involved in this protection, bone marrow chimeras, lacking kinase activity in the immune system or the heart, were studied after transverse aortic constriction. Bone marrow-derived cells from PI3Kγ KD mice were not recruited to wild-type hearts, thus preventing fibrosis and preserving diastolic function. After prolonged pressure overload, chimeras with PI3Kγ KD bone marrow-derived cells showed slower development of left ventricular dilation and higher fractional shortening than controls. Conversely, in the presence of a wild-type immune system, KD hearts displayed bone marrow-derived cell infiltration and fibrosis at early stages but reduced left ventricular dilation and preserved contractile function at later time points. Together, these data demonstrate that, in response to transverse aortic constriction, PI3Kγ contributes to maladaptive remodeling at multiple levels by modulating both cardiac and immune cell functions.

Pharmacological inhibition of c-Jun N-terminal kinase signaling prevents cardiomyopathy caused by mutation in LMNA gene

Mutations in LMNA, which encodes A-type nuclear lamins, cause disorders of striated muscle that have as a common feature dilated cardiomyopathy. We have demonstrated an abnormal activation of both the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) branches of the mitogen-activated protein kinase signaling cascade in hearts from Lmna H222P/H222P mice that develop dilated cardiomyopathy. We previously showed that pharmacological inhibition of cardiac ERK signaling in these mice delayed the development of left ventricle dilatation and deterioration in ejection fraction. In the present study, we treated Lmna H222P/H222P mice with SP600125, an inhibitor of JNK signalling. Systemic treatment with SP600125 inhibited JNK phosphorylation, with no detectable effect on ERK. It also blocked increased expression of RNAs encoding natriuretic peptide precursors and proteins involved in the architecture of the sarcomere that occurred in placebo-treated mice. Furthermore, treatment with SP600125 significantly delayed the development of left ventricular dilatation and prevented decreases in cardiac ejection fraction and fibrosis. These results demonstrate a role for JNK activation in the development of cardiomyopathy caused by LMNA mutations. They further provide proof-of-principle for JNK inhibition as a novel therapeutic option to prevent or delay the cardiomyopathy in humans with mutations in LMNA.

Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins

Autosomal Emery-Dreifuss muscular dystrophy and related disorders with dilated cardiomyopathy and variable skeletal muscle involvement are caused by mutations in LMNA, which encodes A-type nuclear lamins. How alterations in A-type lamins, intermediate filament proteins of the nuclear envelope expressed in most differentiated somatic cells, cause cardiomyopathy is only poorly understood. We demonstrated previously abnormal activation of the extracellular signal-regulated kinase (ERK) branch of the mitogen-activated protein kinase (MAPK) signaling cascade in hearts of Lmna H222P 'knock in' mice, a model of autosomal Emery-Dreifuss muscular dystrophy. We therefore treated Lmna(H222P/H222P) mice that develop cardiomyopathy with PD98059, an inhibitor of ERK activation. Systemic treatment of Lmna(H222P/H222P) mice with PD98059 inhibited ERK phosphorylation and blocked the activation of downstream genes in heart. It also blocked increased expression of RNAs encoding natriuretic peptide precursors and proteins involved in sarcomere organization that occurred in placebo-treated mice. Histological analysis and echocardiography demonstrated that treatment with PD98059 delayed the development of left ventricular dilatation. PD98059-treated Lmna(H222P/H222P) mice had normal cardiac ejection fractions assessed by echocardiography when placebo-treated mice had a 30% decrease. These results emphasize the role of ERK activation in the development of cardiomyopathy caused by LMNA mutations. They further provide proof of principle for ERK inhibition as a therapeutic option to prevent or delay heart failure in humans with Emery-Dreifuss muscular dystrophy and related disorders caused by mutations in LMNA.

Early diagnosis of left ventricular dysfunction following acute myocardial infarct. Doppler echocardiography in a study of its course

The prognosis of acute myocardial infarction depends on the development of left-ventricular dilatation and chronic heart failure. Serial echocardiography was performed on admission and on days 2, 4 and 6, to discover the temporal course of any early myocardial adaptation. There were 78 patients (20 women, 58 men; mean age 59 [49-69] years) with acute myocardial infarction and systemic thrombolysis, first studied up to 4 hours after onset of symptoms. The patients were divided into two groups according to infarct size as measured by creatine kinase ("area under the curve"--AUC); group 1: CK AUC < 12 IU/ml.h; group 2: CK AUC > 12 IU/ml.h. While there was no difference between the two groups on admission and on day 2, filling patterns differed significantly at the end of the first postinfarction week in that maximal early diastolic flow velocity (E) in group 1 was 0.65 m/s, but 0.73 m/s in group 2 (P < 0.05); maximal late diastolic flow velocity (A), group 1: 0.71, group 2: 0.58 m/s (P < 0.01); E/A ratio: 0.89 vs 1.22 (P < 0.001); integrated E/A ratio 1.37 vs 1.77 (P < 0.001), and the atrial component of left-ventricular filling 42 vs 36% (P < 0.001). It is concluded that the serial measurement of left-ventricular filling by Doppler echocardiography in the first post-infarction week can identify patients with impaired left-ventricular function through differences in flow pattern. Drug or interventional treatment can then be started early to prevent further left-ventricular dilatation and in this way improve prognosis.

Epoetin trials: randomised controlled trials don't always mimic observational data

The medical management of stage 3 and 4 chronic kidney disease (CKD) attempts to both slow the rate of progression towards dialysis and prevent the development of secondary complications associated with worsening uraemia. Clinicians attempt to achieve this by targeting blood pressure, lipids, calciumphosphate imbalance (mineral metabolism) and anaemia. Over the past 20 years, there has been a wealth of publications reporting on the associations between uraemic anaemia and the development of left ventricular dilatation and left ventricular hypertrophy (LVH) [1–4], reduced quality of life [5,6] and mortality rates [7], both in the CKD non-dialysis and dialysis populations. In the pre-epoetin era, Silberberg reported an association between the degree of anaemia and LVH and differential mortality rates in dialysis patients in the late 1980s [8]. These findings were extended by Foley and Parfrey et al. [9,10] in a number of publications describing the association of anaemia with LVH, congestive heart failure and mortality. Levin et al. [1–3] extended those observations to patients with varying degrees of renal dysfunction, demonstrating increasing prevalence of LVH, dilatation and heart failure as kidney function declines. In addition, numerous other authors have described the association of haemoglobin and outcomes in CKD populations, prior to dialysis, on dialysis and even post-transplant [11]. Given the biological plausibility that anaemia impacts cardiac structure and function, and outcomes, as well as large amount of observational data that suggested a ‘cause and effect’ between the presence of uraemic anaemia and cardiomyopathy, a series of interventional trials were undertaken. Commencing in the late 1990s, a range of themes were applied to clinical trials to examine different hypotheses: ‘early’ vs ‘late’ correction of anaemia and ‘lower’ vs ‘higher’ haemoglobin levels in both ‘pre-dialysis’ and ‘dialysis’ populations. Two published trials have examined whether prevention of anaemia could reduce or reverse the development of LVH in the non-dialysis CKD population, maintaining appropriate attention to other modifiable risk factors. Despite maintaining haemoglobin higher than 120 g/l in the active group and allowing for a progressive decline in haemoglobin in the control group (90–100 g/l), there was no statistical difference in the left ventricular mass between the groups after 2 years [12,13]. Of note, both studies found relative stability of haemoglobin in the control group, despite previous observations which would have suggested decline. Within the context of the trial, a number of parameters were attended to: blood pressure control, mineral metabolism balance and iron status. The findings suggest that even at relatively advanced stages of renal dysfunction, multiple clinical parameters within the context of a trial may cancel out the impact of anaemia on LVH. An editorial by Strippoli and Craig [14], of the Cochrane Renal Group, referred to this as a potential example of the Hawthorn effect, where patients in trials tend to do well. Nonetheless, it is important to note that in the observational studies, no treatment interventions were undertaken. The observations were undertaken in an unselected population, either in the pre-epoetin era, or prior to the acceptance of multiple risk factor intervention in CKD. Thus the randomized controlled trials have included a group of patients who are different from those on whom the original observations were made. In this edition of NDT, Macdougall and co-investigators [15] applied a different model to pre-dialysis anaemic patients, whereby the control group’s haemoglobin concentration was allowed to decline to lower levels (90 g/l), but were subsequently rescued to the same haemoglobin concentration as the active group. They too were unable to demonstrate Correspondence and offprint requests to: Dr Simon D. Roger, MD, FRACP, Department of Renal Medicine, Gosford Hospital, Gosford 2250, Australia. Email: sroger@nsccah.health.nsw.gov.au

Activation of matrix metalloproteinases precedes left ventricular remodeling in hypertensive heart failure rats: its inhibition as a primary effect of Angiotensin-converting enzyme inhibitor.

Matrix metalloproteinases (MMPs) are activated in dilated failing hearts, and angiotensin-converting enzyme (ACE) inhibition prevents left ventricular (LV) dilatation. However, it remains unclear whether activation of MMPs precedes or is secondary to LV remodeling, and an effect of ACE inhibition on MMPs is unknown. Dahl salt-sensitive rats fed a high-salt diet from 8 weeks served as the hypertensive heart failure (HF) model. LV echo, histological study, measurement of mRNA levels, and gelatin zymography were performed before (at 23 weeks) and after (at 26 weeks) the development of LV dilatation and pulmonary edema. The same procedures were conducted in the HF model rats treated with a subdepressor dose of ACE inhibitor (enalapril 5 mg x kg(-1) x d(-1)) from 9 weeks. Rats fed on normal chow served as age-matched controls. In the untreated HF model rats, gene expression of MMP-2 and MMP-9 and tissue gelatinase activity were elevated at 23 weeks without LV dilatation. LV dilatation, LV systolic dysfunction, and pulmonary edema occurred at 26 weeks, with further enhancement of the expression and activity of MMPs. ACE inhibition prevented such geometrical and functional deterioration. The gene expression and activity of MMPs were suppressed by ACE inhibition at 23 weeks without a decrease in blood pressure, and the suppressive effects continued at 26 weeks. MMPs are likely to trigger and promote LV remodeling, and ACE inhibition directly exerts inhibitory effect on MMPs, leading to the prevention of LV remodeling and dysfunction.

Myocardial Extracellular Matrix Remodeling with the Development of Pacing Induced Congestive Heart Failure: Contributory Mechanisms

The myocardial fibrillar collagens ensure structural integrity of adjoining myocytes, provide the means by which myocyte shortening is translated into overall left ventricular (LV) pump function, and have been postulated to be essential for maintaining alignment of myofibrils within the myocyte through a collagen-integrin-cytoskeletal-myofibril relation. This laboratory has performed a series of studies in order to examine the relationship between changes in myocardial collagen matrix components to LV function and geometry which occurred in a model of congestive heart failure (CHF) induced by chronic rapid pacing. In this model of CHF, indices of LV pump function are reduced and accompanied by significant dilation. LV fibrillar collagen concentration was reduced and salt extractable collagen, which reflects collagen cross-linking, was increased with the development of CHF. LV myocyte adhesion capacity to basement membrane substrates was reduced with pacing CHF. Results from a recently completed series of studies have demonstrated alterations in the expression and activity of the collagenases, or matrix metalloproteinases (MMPs) occur during the progression of CHF. Increased LV myocardial MMP abundance and activity occurred with pacing CHF and were associated with the development of LV dilation, wall thinning, and pump dysfunction. These results suggest that changes within the myocardial extracellular space are a dynamic process and accompany the LV remodeling and dysfunction which occurs with the development of a CHF process. Future studies which define the contributory role of MMP synthesis and activation in the LV remodeling process which occurs in the setting of CHF will likely identify unique therapeutic modalities to slow the progression of this disease process.

Southwestern Internal Medicine Conference: The Multifacetted Role of Angiotensin Converting Enzyme Inhibitors in Congestive Heart Failure

The angiotensin converting enzyme (ACE) inhibitors constitute a major breakthrough in the medical management of congestive heart failure. The incidence of side effects with these agents is surprisingly low when they are used in the appropriate dosage. They produce sustained beneficial hemodynamic and symptomatic improvement in most patients with congestive heart failure and may produce greater symptomatic benefit than digoxin when given as second-line therapy to patients with heart failure on diuretics. Their neurohumoral effects generally are advantageous, resulting in normalization of sodium and potassium balance and a reduction in ventricular arrhythmias. The ACE inhibitors may improve survival in patients with congestive heart failure, and recent data suggest that they may prevent or delay the development of left ventricular dilatation and overt heart failure in patients with asymptomatic left ventricular dysfunction.

Time course of left ventricular dilation after myocardial infarction: Influence of infarct-related artery and success of coronary thrombolysis

Dilation of the left ventricle after myocardial infarction is common, occurs rapidly (within 2 weeks of infarction) and may be self-limited. To evaluate the time course of postinfarction left ventricular dilation and to assess the impact of successful coronary thrombolysis, serial radionuclide left ventricular volume analyses were performed in 36 patients undergoing attempted thrombolysis for acute transmural myocardial infarction. All patients underwent cardiac catheterization, coronary angiography and attempted thrombolysis within 7 h of the onset of symptoms. The site of coronary occlusion was the left anterior descending coronary artery in 17 patients, the right coronary artery in 18 and, in 1 patient, occluded bypass grafts to the right and left circumflex coronary arteries. Attempted reperfusion using a thrombolytic agent was successful in 22 individuals, occurring 5 ± 1 h after the onset of symptoms. Gated radionuclide ventriculography was performed early (mean time 1 day after admission, n = 36), subacutely (mean time 11 days postinfarction, n = 36) and late after infarction (mean time 10.5 months, n = 25), and a geometric technique was used to measure serial left ventricular enddiastolic volume.Left ventricular end-diastolic volume for the entire group increased significantly (p < 0.01) from 153 ± 30 ml at baseline to 172 ± 45 ml (at 11 days) to 220 ± 63 ml (at 10.5 months). Twenty of 36 patients showed >20% increase in left ventricular end-diastolic volume (dilation) with time. This appeared early in seven patients, occurred remote from infarction in seven others and showed a progressive pattern in six. Left ventricular dilation was more frequent and chronic dilation significantly more marked (p < 0.01) in patients with left anterior descending as compared with right coronary artery occlusion. Dilation outcomes and ejection fraction for patients in whom attempted thrombolysis was not successful were similar to findings in patients for whom reperfusion was successful.It is concluded that left ventricular dilation after myocardial infarction is a common, though sometimes late-appearing complication, both more frequent and severe in anterior infarction. Relatively late thrombolysis (5 ± 1 h) in the course of acute myocardial infarction did not prevent subsequent development of left ventricular dilation, most probably because of delayed intervention.

Echocardiographic findings late after myectomy in hypertrophic obstructive cardiomyopathy.

Postoperative echocardiograms of 50 patients undergoing myectomy for hypertrophic obstructive cardiomyopathy between 1965 and 1982 have been evaluated. In 21 patients a comparison with preoperative echocardiograms showed that postoperatively there was a significant reduction of septal and free wall thickness, an increase of left ventricular end-diastolic as well as outflow tract dimensions and a reduction or disappearance of systolic anterior motion of the mitral leaflet. Postoperative examination at intervals greater than 3 years revealed a significant increase of left ventricular and left atrial cavity size with unchanged contractile parameters and little reduction of left ventricular hypertrophy. In 4 of 12 patients evaluated greater than 8 years after myectomy, left ventricular dilatation was observed and 3 of these 4 patients developed congestive heart failure. Development of left ventricular dilatation was independent of whether a transventricular and/or transaortic approach was used for myectomy. These data indicate that the late course after myectomy in hypertrophic obstructive cardiomyopathy may be complicated by dilatation of the left ventricular cavity.

Pathophysiologic observations on premature opening of the aortic valve utilizing a technique for multiplane echocardiographic analysis

The use of a simple technique for multiplane echocardiographic analysis and study of the effect of arrhythmia enabled us to investigate the mechanism of premature opening of the aortic valve in two patients with subacute aortic insufficiency. In one patient, premature opening evolved with the development of left ventricular dilatation and failure. In this case the prematurity of opening in each beat was related to diastolic filling time and was accompanied by septal recoil and by premature closure of the mitral valve. We classified this as the diastolic duration-dependent subgroup. In the second patient, who had a hypertrophied, non-dilated left ventricle, premature opening depended on atrial contraction and was independent of diastolic filling time. This case defined an atrial contraction-dependent subgroup. In the light of these findings we analyzed previously reported cases in patients with acute severe aortic insufficiency. These patients appear to fall into the diastolic duration-dependent subgroup.