Ventricular Wall Hypertrophy Research Articles

ERRATUM

Journal of Veterinary Internal MedicineVolume 23, Issue 1 p. 226-226 Open Access ERRATUM This article corrects the following: Multicentric Lymphoma Mimicking Decompensated Hypertrophic Cardiomyopathy in a Cat T.D. Carter, R. Pariaut, E. Snook, D.E. Evans, Volume 22Issue 6Journal of Veterinary Internal Medicine pages: 1345-1347 First Published online: October 8, 2008 First published: 06 January 2009 https://doi.org/10.1111/j.1939-1676.2008.0261.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat In [1], Figure 1 was cropped incorrectly, omitting key information from the printed version. The correct figure is reproduced below. Figure 1Open in figure viewerPowerPoint Echocardiogram of the right parasternal long-axis (A) and short-axis (B) views showing moderate pericardial effusion and severe concentric hypertrophy of the left ventricular free wall. PE, pericardial effusion; LA, left atrium; LAu, left auricle; LVFW, left ventricular free wall. Reference 1 Carter TD, Pariaut R, Snook E, Evans DE. Multicentric lymphoma mimicking decompensated hypertrophic cardiomyopathy in a cat. J Vet Int Med 2008; 22: 1345– 1347. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Volume23, Issue1January/February 2009Pages 226-226 FiguresReferencesRelatedInformation

Preoperative, postoperative and 1-year follow-up N-terminal pro-B-type natriuretic peptide levels in severe chronic aortic regurgitation: correlations with echocardiographic findings

B-type natriuretic peptide is synthesized in response to increased ventricular wall stress (WS) and hypertrophy. To serially evaluate amino-terminal-pro-BNP (NT-pBNP) serum levels in patients undergoing aortic valve replacement (AVR) for severe chronic aortic regurgitation (AR), blood samples were drawn preoperatively, 15 days postoperatively, at 6- and 12-month follow-up in 25 consecutive patients. Two-dimensional echocardiography was performed concomitantly, assessing left ventricular (LV) dimensional and functional parameters, including WS. Correlations between NT-pBNP, clinical and echocardiographic data were assessed by non-parametric statistics. Median preoperative NT-pro-BNP was 276 pg/ml (IQR=85-1056), being normal or mildly increased in 20 patients, overly increased in five. The most significant correlations of preoperative NT-pBNP were with diastolic (r=0.80, P<0.001) and systolic (r=0.75, P<0.001) meridional WS and inversely with time from symptom onset (r=-0.67, P=0.001). NT-pBNP increased 15 days postoperatively (568 pg/ml, P=0.006 vs. preoperative), then decreased at 6 months (144 pg/ml, P<0.001) to remain stable at 1 year (108 pg/ml, P=0.16). Long-term follow-up NT-pBNP showed direct correlation with diastolic WS (r=0.56, P=0.02). Higher preoperative levels of NT-pBNP predicted greater magnitude of total LV mass regression at follow-up (r=-0.65, P=0.002) independent of preoperative LV mass index, showing that NT-pBNP may have a potential prognostic usefulness in adjunct to echocardiography.

Chronic inhibition of 11beta‐hydroxysteroid dehydrogenase activity reduces cardiovascular comorbidities in corpulent and stroke‐prone SHR

Changes in the secretion or metabolism of cortisol are associated with human hypertension and metabolic disorders. 11beta‐hydroxysteroid dehydrogenase 1 (11β‐HSD1) converts inactive glucocorticoid cortisone to active form cortisol within tissues. We tested the hypothesis that 11β‐HSD1 contributes to the hypertension, insulin resistance, dyslipidemia, and end organ damage in SHR‐SP or obese SHR‐cp rats. Cardiovascular comorbidities were measured before and during 3 weeks of vehicle or compound 11 (10 mg/kg/d) administration in SHR‐cp. In association with significantly decreasing 11β‐HSD1 activity in liver and adipose of obese SHR‐cp, compound 11 significantly reduced hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and hypertension without affecting microalbuminuria or creatinine clearance. In a separate study, cardiovascular comorbidities were measured before and during 8 weeks of high salt and high fat intake in the presence or absence of compound 11 (24 ppm) administration in SHR‐SP. In association with significantly decreasing 11β‐HSD1 activity in liver of SHR‐SP, compound 11 reduced hypertension, plasma LDL and triglycerides, left ventricular wall thickness and hypertrophy, and microalbuminuria. These studies suggest that 11β‐HSD1 plays an important role in the pathogenesis of hypertension, metabolic disorders, and end organ damage.

Preoperative Cardiac and Pulmonary Assessment in Bariatric Surgery

Morbidly obese patients have a high prevalence of known and unknown cardiopulmonary diseases. The aim of this study was to assess the value of cardiopulmonary tests routinely performed before bariatric surgery. The population studied included 67 women and 10 men, aged 39 +/- 10 years, with a body mass index of 43 +/- 4 kg/m2. All patients, candidates for laparoscopic gastric banding, underwent after clinical evaluation: resting electrocardiography (ECG), Doppler-echocardiography, exercise stress testing, Epworth Sleepness Scale, and polysomnography, spirometry, blood gases, and chest x-ray. The ECG demonstrated conduction or ST-T wave abnormalities in 48 patients (62%). Prolongation of the QT interval >10% was found in 13 patients (17%). Stress tests were negative in 56 patients (73%) and were not interpretable in the remaining 21 patients (27%). Doppler-echocardiography showed hypertrophy of the left ventricular posterior wall in 47 patients (61%) without any consequences on perioperative management. Polysomnography showed an obstructive sleep apnea-hypopnea syndrome (OSAHS) in 31 patients (40%), leading to preoperative continuous positive airway pressure (CPAP) treatment in 17 patients (22%). Nevertheless, the Epworth Sleepness Scale was pathological in only 17 patients (22%). Ten patients (13%) presented minor chest x-ray alterations. Spirometry demonstrated an obstructive respiratory syndrome in 13 patients (17%) and a restrictive syndrome in five patients (6%). Hypoxemia <80 mmHg was observed in 21 patients (27%) and hypercapnia >45 mmHg in six patients (8%), without any consequences on the management of the perioperative period. We recommend the preoperative assessment by clinical evaluation, ECG, and polysomnography. For patients with cardiac or pulmonary histories and/or ECG abnormalities, we recommend echocardiography, spirometry, and blood gases.

Mice expressing L345P mutant desmin exhibit morphological and functional changes of skeletal and cardiac mitochondria

Desmin mutations underlie inherited myopathies/cardiomyopathies with varying severity and involvement of the skeletal and cardiac muscles. We developed a transgenic mouse model expressing low level of the L345P desmin mutation (DESMUT mice) in order to uncover changes in skeletal and cardiac muscles caused by this mutation. The most striking ultrastructural changes in muscle from DESMUT mice were mitochondrial swelling and vacuolization. The mitochondrial Ca(2+) level was significantly increased in skeletal and cardiac myocytes from DESMUT mice compared to wild type cells during and after contractions. In isolated DESMUT soleus muscles, contractile function and recovery from fatigue were impaired. A SHIRPA screening test for neuromuscular performance demonstrated decreased motor function in DESMUT compared to WT mice. Echocardiographic changes in DESMUT mice included left ventricular wall hypertrophy and a decreased left ventricular chamber dimension. The results imply that low levels of L345P desmin acts, at least partially, by a dominant negative effect on mitochondria.

Comparison of Afro-Caribbean Patients Presenting in Heart Failure With Normal Versus Poor Left Ventricular Systolic Function

Data suggest that heart failure (HF) in Afro-Caribbean patients may be more often associated with preserved left ventricular (LV) systolic function, LV hypertrophy, and probable LV diastolic dysfunction than in other populations. Echocardiographic results on all patients referred for HF in a contemporary Afro-Caribbean population were reviewed, comparing findings in patients with and without preserved LV systolic function with. Echocardiographic findings included left atrial dimension, LV systolic and diastolic dimensions, ventricular septal and posterior wall thicknesses, right ventricular dimension, valve abnormality, or pericardial effusion. LV shortening fraction and ejection fraction were calculated. Age, gender, and presence of atrial fibrillation were recorded. Results from patients with preserved LV systolic function (LV shortening fraction >0.27) were compared with those with poor LV systolic function. There were 505 patients with HF with adequate studies; mean age +/- SD was 64 +/- 15 years, 46% were men, 17% had atrial fibrillation, and 285 of 505 (57%) had preserved LV systolic function. Those with preserved LV systolic function were no different in age (64 +/- 15 vs 64 +/- 14 years, p = 0.98) but were less likely to be men (40% vs 54%, p <0.01). They were less likely to have a dilated left atrium (61% vs 81%, p <0.001) or increased LV diastolic dimension (8% vs 63%, p <0.001). They were more likely to have increased ventricular septal or posterior wall hypertrophy (84% vs 66%, p <0.001) or other abnormal findings, including an abnormal valve, right ventricular enlargement, increased septal to posterior wall thickness ratio, or pericardial effusion (25% vs 6%, p <0.001). The presence of atrial fibrillation was no different (14% vs 20%, p = 0.10). In conclusion, most Afro-Caribbean patients with HF have preserved LV systolic function with high rates of LV hypertrophy, septal hypertrophy, and other echocardiographic abnormalities.

Perioperative Hypotension due to Systolic Anterior Motion of the Mitral Valve with Left Ventricular Outflow Track Obstruction during Off-Pump Coronary Artery Bypass Surgery - A case report -

Systolic anterior motion of the mitral valve (SAM) is well known in the concentric left ventricular hypertrophy or post mitral valvuloplasty. However, SAM has not been reported in Off-pump coronary artery bypass surgery (OPCAB). Preoperatively, SAM in combination with a left ventricular outflow tract obstruction leads to severe cardiovascular destabilization. Moreover, a diagnosis of SAM is very important because the administration of conventional therapy to hypotension can aggravate SAM. We report a patient with un-identified left ventricular wall hypertrophy or mitral valve regurgitation, who was diagnosed with SAM by TEE during OPCAB. This report describes the diagnostic and therapeutic strategies for the perioperative management of SAM.

Amyloid heart disease mimicking hypertrophic cardiomyopathy*

To investigate the importance of transthyretin (TTR) gene mutations in explaining the phenotypic expression in patients diagnosed with hypertrophic cardiomyopathy (HCM) in northern Sweden. Hypertrophic cardiomyopathy is relatively common and often caused by mutations in sarcomeric protein genes. Mutations in the TTR gene are also common, one of which causes familial amyloid polyneuropathy (FAP), with peripheral polyneuropathy and frequently, cardiac hypertrophy. These circumstances were highlighted by the finding of an index case with amyloidosis, presenting itself as HCM. Initial rectal and fat biopsies did not show amyloid deposits. Later on, the patient was shown to carry a TTR gene mutation, and cardiac amyloidosis was confirmed by myocardial biopsy. Only then was a repeated fat biopsy positive for amyloid deposits. Cross-sectional study. Cardiology tertiary referral centre. Forty-six unrelated individuals with HCM and the index case were included. Common diagnostic criteria for HCM were used. The 46 patients with HCM were previously analysed for mutations in eight sarcomeric protein genes and the TTR gene was now analysed by denaturing high-performance liquid chromatography and direct sequencing. One mutation in the TTR gene (Val30Met) was found in three individuals and the index case. Three of the 46 cases with HCM carried the Val30Met mutation, and were considered likely to have cardiac amyloidosis, like the index case. As a correct diagnosis of cardiac amyloidosis is mandatory for a potentially life-saving treatment, TTR mutation analysis should be considered in cases of HCM not explained by mutations in sarcomeric protein genes.

Yield of Genetic Testing in Hypertrophic Cardiomyopathy

To determine the clinical parameters of hypertrophic cardiomyopathy (HCM) that correlated significantly with the presence of an identifiable sarcomeric mutation. Previous comprehensive mutational analyses of all protein-coding exons of 8 sarcomeric genes revealed pathogenic mutations in 147 (38%) of 389 unrelated patients seen at the HCM outpatient clinic at the Mayo Clinic in Rochester, Minn, between April 1997 and December 2001. Clinical data, extracted from patient records and blinded to patient genotype, were maintained in a custom database. In 389 unrelated patients, younger age at diagnosis, family history of HCM, and Increasing left ventricular wall thickness were all associated with Increased likelihood of identifying an HCM-associated sarcomeric mutation. In contrast, family history of sudden cardiac death, myectomy status, and anatomical subtype did not correlate significantly with genotype-positive status. With use of a simple scoring system based on age at diagnosis, left ventricular wall thickness, and family history of HCM, the likelihood of a sarcomeric mutation could be estimated. Clinical predictors of positive genotype, such as the presence of an implantable cardioverter-defibrillator, age at diagnosis, degree of left ventricular wall hypertrophy, and family history of HCM, may aid in patient selection for genetic testing and increase the yield of cardiac sarcomere gene screening.

LEOPARD Syndrome: Cardiac Imaging Findings

EOPARD syndrome is a rare autosomal dominant hereditary disorder originally described by Gorlin et al. [1] as multiple lentigines syndrome. For clarification and better memorization of the disorder’s aspects, the mnemonic aid LEOPARD was introduced: lentigines, multiple; electrocardiographic conduction defects; ocular hypertelorism; pulmonary stenosis; abnormalities of the genitalia; retardation of growth; and deafness, sensorineural. Most cases with this diagnosis have only a few of the features described, and patients with the full clinical spectrum are very rare. We describe the clinical and cardiac imaging findings in a patient with the full syndrome. The patient’s cardiac involvement was extensively studied, and the following imaging techniques were used: conventional chest Xray, echocardiography, right and left heart catheterization including coronary arteriography, thoracic aortography, and MRI. To our knowledge, this is the first LEOPARD case in the literature that was extensively studied with MRI. Case Report A 17-year-old boy with known LEOPARD syndrome was referred to our center for evaluation of his cardiac status. The patient had mild exertional dyspnea and central and peripheral cyanosis. The patient also had a minor form of lentiginosis that was especially developed on the left side of the neck and in the right axillary region (Fig. 1A). He had hypertelorism and was deaf, and his genitalia were hypoplastic. His body weight and height were 32.4 kg and 143 cm, values typical for a 10-year-old boy. His ECG showed signs of right ventricular hypertrophy, AV block grade 1, and right axis deviation. The chest X-ray showed a slightly enlarged heart with increased retrosternal contact, indicating the presence of right heart hypertrophy. There was dilatation of the main pulmonary and left pulmonary arteries. No evidence of hypercirculation was found. The peripheral pulmonary vasculature was normal. No abnormality of the chest wall and osseous structures was present (Fig. 1B). Echocardiography showed valvular and infundibular pulmonary stenosis with massive hypertrophy of the free right ventricular wall and the septum (Fig. 1C). The gradient measured with a Doppler sonogram over the right ventricular outflow tract (RVOT) was 175 mm Hg, and the mean systolic gradient was 87 mm Hg. The left ventricle was small, left ventricular function was normal, and no gradient was present over the left ventricular outflow tract (LVOT), although there was massive hypertrophy of the septum. In addition, there was a patent foramen ovale and minimal aortic and mitral regurgitation, the latter a result of a prolapse of the anterior leaflet of the mitral valve. Cardiac catheterization showed concentric right ventricular hypertrophy with severe systolic infundibular narrowing and the typical doming sign of the pulmonic valve (Fig. 1D). The right ventricular pressures were 220 mm Hg during systole and 4 mm Hg during end-diastole; the pressures in the pulmonary artery were 28 mm Hg and 4 mm Hg, respectively, with a mean of 14 mm Hg. The pulmonary capillary wedge pressure was 11/0/5 mm Hg. The left ventriculogram showed hypertrophy of the septal portion of

Right ventricle in arterial hypertension

Left ventricular hypertrophy is the best known and most evident cardiac organ manifestation of arterial hypertension. However, only limited findings are available on function and structure of the right ventricle. The published studies show that the right ventricle is also affected in the course of hypertensive heart disease. Particularly hypertrophy of the right ventricular free wall, impaired right ventricular diastolic filling, elevated right ventricular filling pressure as well as impairment of right ventricular ejection fraction in the late phase of arterial hypertension were reported. Possible causes of these structural and functional changes of the right ventricle are (1) translation of the increased left ventricular filling pressure in the pulmonary circulation, (2) interaction of the right and left ventricle, and (3) systemic circulation of cytokines and growth hormones such as angiotensin II, aldosterone, and others.

Spectrum of M-Mode Echocardiographic Abnormalities in 75 Cats With Systemic Hypertension

A retrospective study was performed in 75 hypertensive cats to determine the spectrum and frequency of M-mode echocardiographic abnormalities. Results indicated that 21.3% of the cats had M-mode measurements within normal reference ranges. For cats with echocardiographic abnormalities, changes were variable. Thirty-nine percent of hypertensive cats had hypertrophy of the interventricular septum in diastole, and 41.3% had hypertrophy of the left ventricular (LV) posterior wall in diastole. One cat in five had a dilated left atrium, while fractional shortening and LV internal dimension in diastole were normal in 82.7% and 86.7% of the cats, respectively. The marked variability of echocardiographic findings in hypertensive cats made echocardiography an unreliable screening test for hypertension.

Prevention and management of chronic heart failure in patients at risk

The prevalence and incidence of chronic heart failure (HF) have now reached epidemic proportions. However, the issue of the prevention of HF has been raised only recently. New US guidelines have introduced a new classification system that includes 4 categories: patients at risk, patients with asymptomatic left ventricular dysfunction, patients with symptomatic HF, and those with refractory HF. Because coronary artery disease is the major cause of HF, its risk factors are also those of HF. Hypertension favors the development of HF through accelerated atherosclerosis and increased left ventricular wall stress and hypertrophy. Left ventricular hypertrophy is also a powerful risk factor for HF, independent of blood pressure. Angiotensin-converting enzyme (ACE) inhibitors, β-blockers, and diuretics are the antihypertensive agents that have been associated with favorable effects in patients with overt HF. Therefore, they may be preferred in the prevention of this syndrome. Diabetes is the most frequent noncardiac comorbidity of HF and is independently associated with an increased risk. Normalization of glycemic and glycosylated hemoglobin levels is a desirable goal of treatment. However, no direct evidence exists in the prevention of HF. A greater control of the other risk factors (eg, hypertension, hyperlipidemia) is, on the other hand, particularly important. β-Blockers and ACE inhibitors have both been shown to have favorable effects across all spectrums of severity of HF. The ACE inhibitor ramipril has also been shown to prevent the development of HF in patients at risk without left ventricular dysfunction. The role of antiplatelet agents, warfarin, and statins is clear in the prevention of the coronary artery disease. However, it has not been adequately assessed in patients with HF and awaits the results of ongoing trials.

Cardiac amyloidosis. A disease with many faces and different prognosis

To identify the principal forms of cardiac amiloydosis presentation in a terciary hospital. Eight cases with cardiac amyloidosis were identified. Five were women, their ages ranged from 23 to 83 years (mean 62). After a medical history and clinical examination the patients were submitted to complementary tests: electrocardiogram (EKG), echocardiogram (ECHO), scintigraphy with technecium pirophosphate and cardiac biopsy these results allowed the identification of their clinical situation. Seven patients referred dyspnea, 6 were in heart failure, 1 patient had syncope. The EKG identified complete atrioventricular (AV) block in 4 patients, and antero septal inactive area in the other 4. The ECHO showed normal cardiac diameter in all (mean left ventricular diastolic diameter of 46.8) and slight reduction of left ventricular ejection fraction; hypertrophy of the left ventricular septal and posterior walls in all cases, in 7 cases there was a hyper refractile granular sparkling ECHO. Two different groups were identified: one with complete AV block and the second with restrictive cardiomyopathy. The prognosis was different in these two groups. Those with complete AV block evolved better after pacemaker implantation and those with restrictive cardiomyopathy had refractory heart failure and 3 of them died. The increased free wall and septal thickness, the slight systolic dysfunction and the infiltration aspect at ECHO allow us to identify the great majority of the cases. Those patients with restrictive cardiomyopathy evolve with refractory heart failure and most of them die in a few months.

Age-Related Changes in Cardiac Physiology

The basic mechanisms that cause aging are still poorly understood. Longitudinal prospective population studies using noninvasive examination techniques have improved our ability to differentiate between aging and disease. This review describes some general morphological and functional aging-related changes of the heart that have clinical relevance, and considers the possibility of drug treatment for the manifestations of aging per se. Digitalis has not been shown to improve the aging-related decline in myocardial strength and contractility. During aging, heart tissue stiffens and the speed and extent of diastolic filling decline. The latter is a limiting functional factor, particularly during increases in heart rate. Lowering peripheral vascular resistance, which is often increased in older people, might indirectly improve heart function. However, no drug has been shown to improve myocardial strength or lower tissue stiffness via a direct effect on the heart. It has been claimed, however, that calcium antagonists might improve diastolic filling. Morphological changes during aging are dominated by some left ventricular wall and septal hypertrophy, and left atrial and ventricular widening. Recent findings have suggested that angiotensin II might act as a growth stimulating factor, promoting cardiac hypertrophy. This has led to speculation that ACE inhibitors might contribute to the restructuring of the heart, not only in hypertension but also in patients with the common combination of slightly elevated blood pressure and aging-related myocardial hypertrophy. At present, it appears that improving exogenous factors (e.g. lifestyle, living circumstances and access to adequate medical care) offers greater opportunities for postponing cardiac aging than drugs that directly interfere with the physiological aging of the heart.

Novel Missense Mutation in Cardiac Troponin T Gene Found in Japanese Patient with Hypertrophic Cardiomyopathy

Familial hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy with an autosomal dominant pattern of inheritance. The disease bearing genes for HCM in HCM families have been identified asβ-myosin heavy chain,α-tropomyosin, cardiac troponin T (cTnT) and myosin binding protein-C genes. In the present study, we searched for the mutations in the cTnT gene in Japanese HCM patients. Single-strand conformation polymorphism gel analysis of polymerase chain reaction-amplified product was used to search for the mutations in the exons 8, 9 and 15 of the cTnT gene from 60 familial HCM patients. Clinical studies of the family members were performed and the incidence of sudden or disease-related deaths within the family was also examined. We have identified a novel missense mutation in exon 9 (Ala104Val) of the cTnT gene in a patient with familial HCM. Because the missense mutation was found at the residue conserved through chicken to humans and was not detected in the more than 50 normal controls, it was suggested that this missense mutation is the cause of HCM in this family. Although the affected family members presented moderate hypertrophy of the left ventricular wall, they were symptomatic and there was a high incidence of sudden death in her family members. Among Japanese patients with familial HCM, a novel missense mutation (Ala104Val) in the cTnT gene was identified. Familial HCM is genetically heterogeneous in Japanese HCM patients as observed in Caucasian kindreds. The disease in the kindred was severe and there was a high incidence of sudden or disease-related deaths in the kindred with this mutation.

Echocardiographic findings in 83 patients 13-26 years after intracardiac repair of tetralogy of Fallot.

Doppler echocardiography was performed in 83 patients, 13-26 (median 19) years after repair of tetralogy of Fallot. Median age at repair was 7 years (range 9 months-42 years). An outflow patch restricted to the right ventricle was used in 29%, a transannular patch in 27% and the right ventricle was closed without a patch in 44%. Ninety-six percent of the patients were asymptomatic at follow-up. Patients with a transannular patch were younger, had a larger right ventricle and a higher right ventricle to pulmonary artery pressure difference than those without a patch. The average end-diastolic diameter of the right ventricle was larger than normal regardless of type of repair. The thickness of the right ventricular wall was increased in 50%. In 43% of the patients there was persistent hypertrophy of the right ventricular wall despite normalized systolic pressure. The average size and function of the left ventricle were normal although fractional shortening was reduced in 30% of the patients. The aortic root was abnormally large in 48%. Thirty-four percent had moderate or severe pulmonary valve regurgitation. Symptom-limited work capacity was 87% of predicted and was inversely related to age, systolic pressure in the right ventricle. E/A ratio of the left ventricle and use of the transannular patch. We conclude that right ventricular dysfunction and right ventricular outflow obstruction and/or incompetence were common even in asymptomatic long-term survivors after repair of tetralogy of Fallot.

Left ventricular remodelling after acute myocardial infarction--solved and unsolved issues

Left ventricular remodelling after acute myocardial infarction, through long-term left ventricular chamber dilatation and increased wall stress can result in alteration of the contractile properties of the non-infarct zone, impairment of the systolic and diastolic performances of the left ventricle, and eventually congestive heart failure. Left ventricular remodelling is influenced by several factors, among which the role of systemic and tissue renin angiotensin systems is determinant. Pharmacological interventions on the renin angiotensin systems were shown to limit left ventricular remodelling and reduce mortality from acute myocardial infarction in rats and humans, although the results of some trials remain controversial. To date, the beneficial effects of ACE inhibitors have only been demonstrated in patients with a low residual ejection fraction. Recent observations of changes in left ventricular chamber dilatation and left ventricular wall hypertrophy occurring over the course of time after acute myocardial infarction allow better definition of the subset of patients who are at risk of progressive left ventricular dysfunction and congestive heart failure. An akinetic surface >20%, a left ventricular ejection fraction <0 x 40, an anterior location of the infarction, a stroke volume <31 ml.m(-2) during the acute phase, and persistent occlusion of the infarct-related artery are the most powerful predictors of late left ventricular function impairment. Some issues remain controversial, such as the optimal time for introducing ACE inhibitors after the onset of symptoms, the potential additive effects of ACE inhibitors given in conjunction with thrombolytic therapy, and the role of systemic angioplasty of the infarct-related artery.

Continuous activation of gp130, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice.

To investigate the physiological roles of gp130 in detail and to determine the pathological consequence of abnormal activation of gp130, transgenic mice having continuously activated gp130 were created. This was carried out by mating mice from interleukin 6 (IL-6) and IL-6 receptor (IL-6R) transgenic lines. Offspring overexpressing both IL-6 and IL-6R showed constitutive tyrosine phosphorylation of gp130 and a downstream signaling molecule, acute phase response factor/signal transducer and activator of transcription 3. Surprisingly, the distinguishing feature of such offspring was hypertrophy of ventricular myocardium and consequent thickened ventricular walls of the heart, where gp130 is also expressed, in adulthood. Transgenic mice overexpressing either IL-6 or IL-6R alone did not show detectable myocardial abnormalities. Neonatal heart muscle cells from normal mice, when cultured in vitro, enlarged in response to a combination of IL-6 and a soluble form of IL-6R. The results suggest that activation of the gp130 signaling pathways leads to cardiac hypertrophy and that these signals might be involved in physiological regulation of myocardium.

Intracellular signaling and genetic reprogramming during agonist-induced hypertrophy of cardiomyocytes.

Cardiac myocytes stop dividing shortly after birth and subsequently the heart grows by enlargement of individual cells, a process that can be observed in vitro as well.' However, growth of individual cardiomyocytes can also be observed in the adult heart, a process called hypertrophy. Chronic hernodynamic overload of the heart by, e.g. , infarction, hypertension or volume or pressure overload ultimately leads to hypertrophy of the left ventricular wall. The hypertrophy process involves induction of transcription of specific contractile as well as noncontractile protein genes resulting in growth as well as change in contractile function of the c a r d i o r n y o ~ y t e . ~ ~ ~ This allows the heart to maintain normal beat-to-beat volume under the circumstances mentioned above. Although only limited evidence was presented for their importance during in vivo development of hypertr~phy,~-' hormonal and mechanical stimuli are thought to be the initial signals that trigger the onset of cell growth. The evidence for the involvement of hormonal and mechanical signals in the induction of hypertrophy mainly comes from in vitro models employing cultured neonatal cardiomyocytes. Here it was shown that induction of hypertrophy is accompanied by activation of the phosphoinositide (PI) cycle and by rapid stimulation of transcription of so-called immediate early genes, transcription factors, ultimately leading to rearrangement of gene expression of structural proteins in the cardiomyocyte. Recently, studies of hypertrophy were also performed on cultured adult cardiomyocytes,8-'1 confirming results from the neonatal cardiomyocyte model. In this review we focus on the influence of these hormonal and mechanical signals that activate the PI cycle during development of hypertrophy in the model of cultured cardiomyocytes and the ultimate outcome