Hypertrophy – ABC CARDIOL

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Research Letter

Conflicting Clues in Severe LV Hypertrophy: An Unusual Presentation of ATTR Amyloidosis

Ana Sofia Nogueira Fernandes et al. João Faria Catarina Ferreira Vieira

Introduction

In recent decades, major advances have reshaped the clinical and epidemiological understanding of transthyretin (TTR) cardiac amyloidosis (ATTR). Progress in cardiovascular imaging has enabled earlier and more accurate identification of the disease. In particular, bone scintigraphy with ⁹⁹mTc-labeled tracers has markedly simplified the non-invasive diagnosis of ATTR cardiomyopathy, substantially reducing the need for endomyocardial biopsy in most cases.^, Nevertheless, diagnostic challenges may arise when clinical, genetic, and imaging findings are discordant. We report a case of biopsy-proven hereditary ATTR (ATTRv) cardiomyopathy with negative bone scintigraphy, illustrating an important diagnostic pitfall within the contemporary diagnostic algorithm.

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Editorial

LncRNA ZEB1-AS1: A New Player in Epigenetic Control of Cardiac Hypertrophy

Fernando R. Giugni

Cardiac hypertrophy represents a fundamental adaptive response of the myocardium to hemodynamic stress. Although initially compensatory, persistent hypertrophy predisposes to maladaptive remodeling, diastolic dysfunction, and ultimately heart failure. Despite substantial progress in neurohormonal blockade and blood pressure control, therapies directly targeting the molecular mechanisms that sustain pathological hypertrophy remain limited. In recent years, growing attention has turned toward noncoding RNAs—particularly long noncoding RNAs (lncRNAs)—as regulators of cardiomyocyte growth, contractility, and survival.^, Understanding how these molecules orchestrate gene expression and chromatin remodeling offers new opportunities to modulate the hypertrophic process at its regulatory core.

While several lncRNAs such as TUG1, NEAT1, and PVT1 have been linked to the hypertrophic response, the diversity of these transcripts and the context-specificity of their effects suggest that many key regulators remain unidentified. Among these, ZEB1-AS1, originally characterized in cancer biology as a modulator of cell proliferation and migration, had not been studied in the heart. Whether this lncRNA contributes to cardiac remodeling, and through which molecular intermediates, remains unknown.

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Viewpoint

Clinical Reasoning and Classification of Cardiomyopathies

Vagner Madrini Junior et al. Evandro Tinoco Mesquita Diane Xavier de Avila Fabio Fernandes

Definition

Cardiomyopathies (CMPs) are a group of diseases with multiple etiologies and heterogeneous phenotypes, ranging from microscopic changes in cardiomyocytes in asymptomatic patients to cases of fulminant heart failure with fluid retention, and perfusion and heart rhythm changes. A CMP was initially defined as a heart muscle disease caused by genetic defects, myocyte injury or myocardial infiltration, and characterized by structural and functional abnormalities in the absence of congenital disease, valvular disease or hypertension. The initial approach of patients with CMP consists of clinical evaluation and complementary imaging techniques and genetic testing, in search of diagnostic evidence and the need for specific tests ().^,

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Editorial

Focusing on the Right Ventricle in PRKAG2 Syndrome

Luís Rocha Lopes

The PRKAG2 gene encodes the adenosine monophosphate-activated protein kinase (AMPK) gamma 2 regulatory subunit. AMPK has a central role in cellular energy homeostasis. Pathogenic variation in PRKAG2 causes an autosomal dominant syndrome comprising ventricular hypertrophy, supraventricular arrhythmias, electrocardiographic pre-excitation and conduction system abnormalities.^– The genetic background of this syndromic presentation was discovered in 2001.. Histologically there is myocyte glycogen accumulation, and the typical pattern of hypertrophy is usually described as biventricular and concentric, similar to other metabolic phenocopies of hypertrophic cardiomyopathy (HCM), with systolic dysfunction as another possible “red-flag” feature. The more frequent pathogenic variants are p.Arg302Gln and p.Asn488Ile. Due to the condition’s rarity, most publications consist of small case series or case reports, with few exceptions.. None of the previous publications specifically report right ventricular imaging findings in this condition.

Expanding on their previous work, where 3D echocardiography and strain imaging findings of the left ventricle were described in a cohort of 30 patients with PRKAG2 syndrome, Pena et al. provide a short report focusing on the right ventricle (RV), using the same cohort, in the current edition of this Journal.

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Original Article

Echocardiography on Prehypertension and Stage I Hypertension

Carolina Bertoluci et al. Murilo Foppa Angela Barreto Santiago Santos Sandra C. Fuchs Flávio Danni Fuchs

Abstract

Background

Prehypertension and stage I hypertension are associated with left ventricular (LV) remodeling. In this study, we compared echocardiographic parameters of preclinical hypertensive target organ damage in individuals with prehypertension and stage I hypertension selected from the same population.

Methods

We compared baseline echocardiogram measurements of participants included in the PREVER study with prehypertension (PREVER-prevention; n=106) or stage I hypertension (PREVER-treatment; n=128). Sex-specific differences in echocardiographic parameters were also investigated.

Results

Mean systolic and diastolic BP were significantly higher in the stage I hypertension group (141.0/90.4 mmHg) than in the prehypertension group (129.3/81.5 mmHg, P<0,001 for both). Mean age was 55 years old (30 to 70), with an almost equal number of men and women, of which 80% were white and 7% had diabetes. Most parameters of LV mass, LA size and diastolic function were similar between the prehypertension and stage I hypertension groups. Hypertensive individuals had larger LA diameter and posterior wall thickness, and lower lateral e’ velocities, even after adjustment for age, sex and body mass index. Sex-specific analysis showed higher LV mass in stage I hypertension compared to prehypertension only in women (141.1 ± 34.1 g vs. 126.1 ± 29.1 g, P<0.05).

Conclusions

In middle-aged individuals with low cardiovascular risk, differences in echocardiographic parameters related to target organ damage are likely subtle between prehypertension and stage I hypertension, although women with stage I hypertension had significantly higher LV mass, which may indicate sex-specific adaptive response to blood pressure in earlier stages of hypertension.

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Artigo Original

Accuracy of chest radiography plus electrocardiogram in diagnosis of hypertrophy in hypertension

Sergio Marrone Ribeiro et al. José Morceli Renato Souza Gonçalves Roberto Jorge da Silva Franco … Francisco Habermann Domingos Alves Meira Beatriz Bojikian Matsubara

BACKGROUND: Chest radiography and electrocardiogram have been criticized due to their low sensitivity for Left Ventricular Hypertrophy diagnosis compared to echocardiogram. This one, however, is not available in primary health care centers to all hypertensive population. OBJECTIVE: To evaluate whether the association chest radiography-electrocardiogram provides the accuracy to justify its use in left ventricular hypertrophy detection in hypertensive patients, as well as the usefulness of the cardiothoracic ratio and oblique radiographs in relation to frontal and lateral views in evaluating dimensions of left cardiac chambers. METHODS: This was a prospective study including 177 consecutive hypertensive patients through chest radiography, electrocardiogram and echocardiography. Accuracy test was used to compare these methods using echocardiography as gold standard. RESULTS: The cardiothoracic ratio showed 17% sensitivity for detection of left ventricular hypertrophy, only indicating cardiac alterations at an advanced stage. Frontal plus lateral views showed sensitivity of 52%, which rose to 54% when chest radiography was associated with electrocardiogram. The oblique views did not significantly improve chest radiography accuracy. Chest radiography presented high specificity and elevated sensitivity for detection of aortal enlargement. Interestingly, this alteration was present in half of the hypertensive patients with left ventricular hypertrophy. CONCLUSION: We conclude that the association chest radiography-electrocardiogram is useful for the screening of hypertensive patients for the diagnosis of left ventricular hypertrophy, especially if echocardiogram is unavailable. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)

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Artigo Original

Impact of hypertension on ventricular remodeling in patients with aortic stenosis

João Carlos Hueb et al. João T. R. Vicentini Meliza Goi Roscani Daniéliso Fusco … Ricaro Mattos Silméia Garcia Zanatti Katashi Okoshi Beatriz B. Matsubara

BACKGROUND: Left ventricular hypertrophy (LVH) is a marker of increased cardiovascular risk and is frequently associated with both arterial hypertension (AH) and aortic stenosis (AoS). Also, these two maladies may co-exit in a same patient. However, in these cases, it is not clear the impact of each one in LVH. OBJECTIVE: To evaluate LVH and ventricular geometry in patients with AS associated or not with arterial hypertension. METHODS: This was a retrospective, observational and transversal study, including 298 consecutive patients with echocardiographic diagnosis of AoS. LVH was defined as myocardial mass > 224g for men and > 162g for women. Patients were classified as having mild (peak gradient 50 mmHg) AoS and separated into two subgroups: with and without hypertension. RESULTS: AH was associated with increased ventricular mass in all three levels of aortic stenosis (mild AS: 172 ± 45g vs 223 ± 73g, p < 0.0001 moderate AoS: 189 ± 77 g vs 245 ± 81g, p = 0.0313 severe AoS: 200 ± 62g vs 252 ± 88g, p = 0.0372), and increased risk of LVH (OR = 2.1 CI95%:1.2-3.6 p = 0.012). Regarding to geometric remodeling, hypertensive patients with severe AS presented a significant increase in frequency of concentric hypertrophy, when compared with those without hypertension (p = 0.013). CONCLUSION: Hypertension is an additional factor of increased left ventricular mass in patients with AS. Also, hypertension was influential in ventricular geometry.

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Anatomopathological Session

Case 5/2010: a 41 year-old man with myocardial hypertrophy who evolved with congestive heart failure

Rafael Moura de Almeida et al. Lucas José Tachotti Pires José Soares Júnior Wilson Ichiki … Wilson André Ichiki Léa Maria Macruz Ferreira Demarchi

ANATOMOPATHOLOGICAL SESSION

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Artigo Original

Ventricular mass and electrocardiographic criteria of hypertrophy: evaluation of new score

Cléber do Lago Mazzaro et al. Francisco de Assis Costa Maria Teresa Nogueira Bombig Bráulio Luna Filho … Ângelo Amato Vincenzo de Paola Antonio Carlos de Camargo Carvalho William da Costa Francisco Antonio Helfenstein Fonseca Rui Manoel dos Santos Póvoa

BACKGROUND: The left ventricular hypertrophy (LVH) is an important and independent cardiovascular risk factor. There is a scarcity of studies in Brazil designed to test the efficacy of the electrocardiogram (ECG) in the diagnosis of this important pathological process. OBJECTIVE: To evaluate a new electrocardiographic score for the diagnosis of LVH by ECG: the sum of the highest amplitude of the S wave and the highest amplitude of the R wave on the horizontal plane, multiplied by the result of the QRS duration [(S+R) X QRS)] and comparing it with the classic electrocardiographic criteria. METHODS: The echocardiograms and ECG of 1,204 hypertensive patients receiving outpatient care were evaluated. The left ventricular mass index (LVMI) was assessed by the echocardiogram, with a diagnosis of LVH when the LVMI was > 96 g/m² for women and > 116 g/m² for men. Four classic criteria of LVH were analyzed at the ECG, in addition to the new score to be tested. RESULTS: In general, the studied ECG-LVH criteria showed significant statistical correlation to the echocardiographic LVMI. The (R+S) X QRS index, using 2.80 mm.s as the cutoff value, provided test accuracy regarding sensibility and specificity of 35.2% and 88.71%, respectively, representing the best correlation to LVMI (r=0.564) when compared to the other indexes: Romhilt-Estes (r=0.464); Sokolow-Lyon (r=0.419); Cornell voltage (r=0.377); Cornell product r=0.444). CONCLUSION: All the electrocardiographic criteria used for the assessment of the LV mass presented low sensitivity. The new score presented the best correlation with LVMI when compared to the other indexes.

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Artigo Original

Pulse pressure measured by home blood pressure monitoring and its correlation to left ventricular mass index

André De Marco et al. Audes Magalhães Feitosa Marco Mota Gomes Giordano Bruno Parente Edgar Guimarães Victor

OBJECTIVE: Measure the systolic (SP), diastolic (DP) and pulse pressure (PP) using home blood pressure monitoring (HBPM) and correlate its values with the left ventricular mass index (LVMI). METHODS: In 2004, 127 individuals underwent HBPM in a private clinic. A total of 83 of these also underwent an echocardiographic study in a period shorter than 6 months. After excluding those with dilated or ischaemic cardiomyopathy and those with mitral or aortic valvopathies, 72 patients were evaluated for the correlation between SP, DP and PP (SP minus DP) and the LVMI. RESULTS: The group’s mean age was 51.9 ± 17.3 years and the masculine gender represented 43% of their components. The mean body mass index (BMI) was 28.6 ± 6 kg/m² and 53% of the patients were using antihypertensive drugs. The PS and PP correlated positively to the LVMI (r = 0.356; p = 0.002 e r = 0.429; p < 0.001, respectively). There was no correlation between DP and LVMI. CONCLUSION: The PS and the PP correlate positively to the LVMI.

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Artigo Original

Cardiac and metabolic characteristics in long distance runners of sport and exercise cardiology outpatient facility of a tertiary hospital

Luciene Ferreira Azevedo et al. Patrícia Chakur Brum Dudley Rosemblatt Patrícia de Sá Perlingeiro … Antônio Carlos Pereira Barretto Carlos Eduardo Negrão Luciana Diniz Nagem Janot de Matos

OBJECTIVE: To characterize electrocardiographic and functional cardiac parameters and cardiopulmonary responses to exercise in long-distance Brazilian runners monitored at the Sport and Exercise Cardiology Outpatient Facility of a tertiary care hospital. METHODS: Of an initial population of 443 male and female athletes of different sport modalities, we assessed 162 (37%) long-distance male runners, aged from 14 to 67. Electrocardiographic (12 leads) and echocardiographic (M-mode and two-dimensional) parameters were recorded at rest. Cardiopulmonary responses were evaluated on a treadmill with a ramp protocol. RESULTS: Metabolic alterations and cardiovascular diseases were diagnosed in 17% and 9% of the runners, respectively. Sinus bradycardia and left ventricular hypertrophy were observed in 62% and 33% of the runners, respectively. Structural alterations such as ventricular cavity > 55mm, relative wall thickness > 0.44, and ventricular mass index > 134g/m2 were found in 15%, 11% and 7% of the runners, respectively. Ejection fraction < 55% was observed in 4% of the runners. Peak oxygen uptake (VO2peak) decreased as of the age of 41, although the anaerobic threshold relative to the VO2peak remained unchanged with age. CONCLUSION: Resting bradycardia and left ventricular hypertrophy are the most frequent cardiovascular adaptations in Brazilian long distance runners monitored by the Sport and Exercise Cardiology Outpatient Facility. Although VO2peak decreases after the age of 41, the relative oxygen uptake at the anaerobic threshold of these runners remained unchanged.

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Artigo Original

Blockade of renin-angiotensin system attenuates cardiac remodeling in rats undergoing aortic stenosis

Giancarlo Gonçalves et al. Leonardo A. M. Zornoff Henrique B. Ribeiro Marina P. Okoshi … Fernando R. S. Cordaro Katashi Okoshi Carlos R. Padovani Flávio F. Aragon Antonio C. Cicogna

OBJECTIVE: To assess the role of the AT1 receptor blocker and the angiotensin-converting enzyme inhibitor in cardiac remodeling induced by aortic stenosis in rats. METHODS: Wistar rats were divided into the following 4 groups: 1) C – control (n=13); 2) AoS – aortic stenosis (n=11); 3) LIS – AoS treated with lisinopril, 20 mg/kg/day (n=11); and 4) LOS – AoS treated with losartan, 40 mg/kg/day (n=9). The treatments were initiated 3 days before surgery. After 6 weeks, the animals underwent echocardiographic study, and quantification of the hydroxyproline (HOP) concentration and the left ventricular (LV) myocyte cross-sectional area (CSA). RESULTS: Aortic stenosis induced an increase in left ventricular wall thickness. The LIS and LOS groups showed no difference as compared with the control group. The AoS and LIS rats had greater left atrial diameters than the control rats did, while no difference was observed in the LOS animals. The AoS animals had greater values of shortening percentage than control animals did. This fact was modified with neither LIS nor LOS. The cross-sectional area of the animals in the AoS group was greater than that in the control group. However, treatment with LOS and LIS attenuated the AoS-induced increase in area. Aortic stenosis caused an increase in HOP concentration, while the LOS group showed no difference as compared with the control group. CONCLUSION: Blockade of the renin-angiotensin system with AT1 blocker and ACEI may attenuate the development of heart hypertrophy, but only the blockade of AT1 receptors attenuates left ventricular interstitial fibrosis.

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Artigo Original

Chronic cigarette smoke exposure results in cardiac remodeling and impaired ventricular function in rats

Édson Castardeli et al. Sergio A. R. Paiva Beatriz B. Matsubara Luiz S. Matsubara … Marcos F. Minicucci Paula S. Azevedo Álvaro O. Campana Leonardo A. M. Zornoff

OBJECTIVE: To determine the cardiac structural and functional alterations caused by cigarette smoke exposure in rats. METHODS: The animals were randomly distributed into the following 2 groups: 1) smokers (S), comprising 10 animals exposed to cigarette smoke at a rate of 40 cigarettes/day; and 2) control (C), comprising 10 animals not exposed to cigarette smoke. After 4 months, the animals underwent morphological and functional study with echocardiography. The variables studied were analyzed by use of the t test or the Mann-Whitney test. RESULTS: The smoking rats had a greater left atrium (S=4.2±0.7mm; C=3.5±0.6mm; P<0.05), and greater left ventricular diastolic (S=7.9±0.7mm; C=7.2±0.5mm; P<0.05) and systolic (S=4.1±0.5; C=3.4±0.5; P<0.05) diameters. The left ventricular mass index was greater in the smoking animals (S=1.5mg/kg±0.2; C=1.3mg/kg±0.2; P<0.05), and the ejection fraction (S=0.85±0.03; C=0.89±0.03; P<0.05) and the shortening fraction (S=47.8%±3.7; C=52.7%±4.6; P<0.05) were greater in the control group. No differences were observed in the diastolic transmitral flow variables (E wave, A wave, and E/A ratio). CONCLUSION: Chronic cigarette smoke exposure results in cardiac remodeling with a decrease in ventricular functional capacity.

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Artigo Original

The early administration of growth hormone results in deleterious effects on ventricular remodeling after acute myocardial infarction

José G. Mill et al. Leonardo A. M. Zornoff Marina P. Okoshi Katashi Okoshi … Carlos R. Padovani Mário Sugisaki Cláudia M. Leite Antônio C. Cicogna

OBJECTIVE: To assess the effect of growth hormone (GH) on myocardial remodeling in infarcted rats. METHODS: This study comprised 24 Wistar rats divided into 3 groups as follows: 1) AMI-GH group – comprising 8 rats that underwent infarction and were treated with GH; 2) AMI group – comprising 8 rats that underwent infarction and received only the diluent of the GH solution; and 3) control group (C group) – comprising 8 rats that underwent simulated infarction. After 30 days, the animals underwent functional study through echocardiography, and the changes in myocardial contractility of the isolated left ventricular (LV) papillary muscle were studied. RESULTS:The echocardiography identified an increase in the diastolic (C=7.32±0.49; AMI=8.50±0.73; AMI-GH=9.34±0.73; P<0.05) and systolic (C=3.38±0.47, AMI=5.16±1.24; AMI-GH=5.96±1.54; P<0.05) diameters (mm) in the LV of the infarcted animals. The AMI-GH group animals had a lower ejection fraction (%) (C=0.9±0.03; AMI=0.76±0.12; AMI-GH= 0.72± 0.14; P<0.05 for C vs AMI-GH) compared with those in controls. The study of the isolated left ventricular papillary muscle showed that the AMI-GH group had changes (C= 1.50±0.59; AMI= 1.28±0.38; AMI-GH=1.98±0.41; P<0.05 for C vs AMI-GH) only in the tension at rest (TR – g/mm²) and in the time delta for a 50% decrease in the tension developed (TR50, ms) after stimulation with calcium (C=23.75±9.16; AMI=-16.56±14.82; AMI-GH=-4.69±8.39; P<0.05 for C vs AMI-GH) and in the delta of tension developed (TD, g/mm²) after stimulation with isoproterenol (C=0.99±0.17; AMI=0.54±0.62; AMI-GH=0.08±0.75; P<0.05 for C vs AMI-GH) compared with those in control animals. CONCLUSION: The early administration of GH in the experimental infarction model in rats may result in adverse effects on the process of ventricular remodeling.

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Original Article

An analysis of electrocardiographic criteria for determining left ventricular hypertrophy

Carlos Alberto Gasperin et al. Helio Germiniani Carlos Roberto Facin Admar Moraes de Souza Cláudio Leinig Pereira da Cunha

OBJECTIVE: To determine the most sensitive criterion for the detection of left ventricular hypertrophy according to echocardiographically defined left ventricular mass. METHODS: The Sokolow-Lyon voltage, Sokolow-Lyon-Rappaport, Cornell voltage duration product, White-Bock, and Romhilt-Estes point scoring criteria were compared with left ventricular mass index, corrected for body surface, obtained from the echocardiograms of 306 outpatients (176 females, 130 males), of all age groups. RESULTS: The Cornell voltage duration product criteria index had the greatest sensitivity in women (54.90%), and the Sokolow-Lyon-Rappaport index was most sensitive in men (73.53%). When applied to men at the same voltage amplitude (20mm) as that in women, the Cornell index showed increased sensitivity relative to the conventional index (28mm) of 67.65% (P<=0.01) and a sensitivity similar to that of the Sokolow-Lyon-Rappaport index, with higher specificity (P<=0.01). The White-Bock and Romhilt-Estes criteria were the least sensitive in men and women, despite their high specificity. The electrocardiographic criteria were more efficient when dilatation predominated over left ventricular hypertrophy. CONCLUSION: The Cornell index had greater sensitivity in women, and the Sokolow-Lyon-Rappaport index was more sensitive in men. When applied to men at the same voltage amplitude as that of women, the Cornell index had an increase in sensitivity similar to that of the Sokolow-Lyon-Rappaport index.

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Artigo Original

Myocardial function during the transition from compensated left ventricular hypertrophy to failure

Antonio Carlos Cicogna et al. Kathleen G. Robinson Chester H. Conrad Robin Squire … Marina P. Okoshi Oscar H. L. Bing

PURPOSE: To investigate the participation of contractile state and relaxation in cardiac muscle dysfunction during the transition from stable hypertrophy to cardiac decompensation in aging spontaneously hypertensive rats (SHR). METHODS: Isolated left ventricular papillary muscle function was studied in SHR with heart failure (SHR-F), in age-matched SHR without evidence of heart failure (SHR-NF), and in nonhypertensive controls Wistar-Kyoto rats (WKY). Muscles were analised in isometric and isotonic contractions in Krebs-Henseleit solution with calcium concentration of 1.25mM at 28ºC. RESULTS: Papillary muscles from SHR-F and SHR-NF demonstrated decreased active tension development and shortening velocity relative to normotensive WKY (p<0.05). SHR-F and SHR-NF did not differ. Compared with SHR-NF and WKY, muscle passive stiffness was increased in the failing SHR (p0.05). CONCLUSION: These data suggest that the progression from stable hypertrophy to heart failure is associated with changes in the passive stiffness and is not related to depression of myocardial contractile function.

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