A dispneia por esforço é uma queixa comum de pacientes com insuficiência cardíaca com fração de ejeção preservada (ICFEP) e doença pulmonar obstrutiva crônica (DPOC). A ICFEP é comum na DPOC e é um fator de risco independente para a progressão e exacerbação da doença. A detecção precoce, portanto, tem grande relevância clínica. O objetivo deste estudo foi detectar a frequência de ICFEP mascarada em pacientes com DPOC não grave com dispneia aos esforços, sem doença cardiovascular manifesta, e analisar a correlação entre ICFEP mascarada e os parâmetros do teste cardiopulmonar de exercício (TCPE). Aplicamos o TCPE em 104 pacientes com DPOC não grave com dispneia aos esforços, sem doença cardiovascular evidente. A ecocardiografia foi realizada antes e no pico do TCPE. Os valores de corte para disfunção diastólica ventricular esquerda e direita induzida por estresse (DDVE/DDVD) foram E/e’ >15; E/e’ >6, respectivamente. A análise de correlação foi feita entre os parâmetros do TCPE e o estresse E/d’. Valor de p<0,05 foi considerado significativo.2 e pulso de O2 mais baixos, além de apresentarem redução na eficiência ventilatória (maiores inclinações de VE/VCO2). Nenhum dos parâmetros do TCPE foram correlacionados com E/e’ DDVE/DDVD induzida por estresse. 64% dos pacientes tinham DDVE induzida por estresse; 78% tinham DDVD induzida por estresse. Ambos os grupos com estresse DDVE e DDVD obtiveram carga menor, V’O Há uma alta prevalência de disfunção diastólica induzida por estresse em pacientes com DPOC não grave com dispneia aos esforços, sem doença cardiovascular evidente. Nenhum dos parâmetros do TCPE se correlaciona com E/e’ induzida por estresse. Isso demanda a realização de Ecocardiografia sob estresse por exercício (EES) e TCPE para detecção precoce e manejo adequado da ICFEP mascarada nesta população. :259-265) Trata-se de um fator de risco cardiovascular independente que contribui para o desenvolvimento de disfunção diastólica.3 Dispneia e intolerância ao exercício são sintomas comuns da DPOC e disfunção diastólica.4 Estudos recentes com grandes coortes de pacientes identificaram um fenótipo cardiovascular em pacientes com DPOC que apresentam curso clínico e prognóstico diferentes.5 O diagnóstico e o manejo precoces são, portanto, muito importantes do ponto de vista clínico.As anormalidades cardiovasculares são comuns na doença pulmonar obstrutiva crônica (DPOC).9A combinação de ecocardiografia sob estresse por exercício (EES) e TCPE é uma abordagem confiável para identificar pacientes com insuficiência cardíaca mascarada pela fração de ejeção preservada (ICFEP). Além disso, os resultados das medições invasivas são comparáveis aos dados obtidos em estudos não invasivos durante o EES.10O teste cardiopulmonar de exercício (TCPE) pode distinguir dispneia cardíaca e respiratória ou diminuição da atividade física.Os objetivos de nosso estudo foram: 1) detectar a frequência de disfunção diastólica subclínica do ventrículo esquerdo (VE) e do ventrículo direito (VD) em pacientes com DPOC não grave sem doença cardiovascular; 2) estabelecer uma correlação entre exercício cardiopulmonar e os parâmetros ecocardiográficos para disfunção diastólica (E/e’).1>50%). Todos os indivíduos apresentavam dispneia aos esforços, mas um total de 104 pacientes  foram considerados elegíveis, assumindo-se os critérios de exclusão. O período de recrutamento foi entre maio de 2017 e abril de 2018, e foi aprovado pelo Comitê de Ética local (protocolo 5/12.03.2018). Todos os participantes assinaram o termo de consentimento livre e esclarecido antes do início do estudo.Este foi um estudo retrospectivo realizado com 224 pacientes ambulatoriais clinicamente estáveis com diagnóstico de DPOC no Hospital Universitário de Doenças Respiratórias “St. Sophia”, Sofia. Apenas 163 deles atenderam aos critérios de inclusão para DPOC não grave: volume expiratório forçado no primeiro segundo maior que 50% (VEFForam considerados os seguintes critérios de exclusão: 1) fração de ejeção do ventrículo esquerdo (FEVE) <50%; 2) disfunção diastólica do ventrículo esquerdo em repouso superior ao primeiro grau; 3) achados ecocardiográficos sugerindo hipertensão pulmonar , velocidade máxima do jato >2,8 m/s; 4) cardiopatia valvar; 5) cardiomiopatia documentada; 6) hipertensão grave não controlada ; 7) fibrilação atrial ou arritmia ventricular maligna; 8) doença isquêmica do coração; 9) anemia; 10) diabetes mellitus; 11) câncer; 12) doença renal crônica (DRC); 13) cirurgia torácica ou abdominal recente; 14) exacerbação recente (nos últimos três meses); 15) mudança recente (nos últimos três meses) na terapia médica.11 Apenas pacientes com obstrução leve a moderada das vias aéreas (VEF1> 50%) foram selecionados.Todos os indivíduos foram submetidos a um exame clínico preliminar, incluindo radiografia de tórax, espirometria, eletrocardiografia e ecocardiografia. Os pacientes elegíveis para o estudo realizaram espirometria e teste ergométrico em Vyntus, teste cardiopulmonar de exercício , de acordo com as diretrizes da European Respiratory Society (ERS).6 Após dois minutos de pedalada sem carga (fase de repouso 0W), seguiu-se uma fase de aquecimento de três minutos (20W). A fase de teste incluiu incrementos de carga de 20W/2min. Os pacientes foram orientados a pedalar a 60 rotações por minuto.Um protocolo em rampa contínua foi aplicado de acordo com diretrizes.2 foi expresso como o maior valor médio de 30 segundos, obtido na última etapa do teste de esforço. Os valores de pico de VO2 são expressos como -O2 ml/kg/min. A eficiência ventilatória (EV/VCO2) foi medida pelo método V-slope. O pico da razão de troca respiratória (pRTR) foi o maior valor médio de 30 segundos no último estágio do teste. RTR >1,10 ao final do teste EES-TCPE foi considerado como esforço máximo.Os gases expiratórios foram coletados respiração a respiração. O pico de VO13 Incidências apicais de quatro câmaras foram usadas para medir os volumes das câmaras com base na regra modificada de Simpson e a fração de ejeção do VE foi considerada preservada se >50%. A análise da ecocardiografia Doppler tecidual foi realizada na dimensão septo-lateral do anel mitral e na dimensão lateral do anel tricúspide para avaliar as ondas sistólica (S) e diastólica miocárdica  do VE e VD. O valor E’ foi usado como média das medições mediais e laterais. O pico da razão E/e’ >15 foi considerado um marcador para disfunção diastólica ventricular esquerda induzida por estresse.Foram realizados ecocardiografia modo M, bidimensional com Doppler.14A função sistólica do ventrículo direito foi avaliada por meio da excursão sistólica do plano do anel tricúspide (TAPSE) e da velocidade de pico S do Doppler tecidual. A espessura da parede do ventrículo direito (EPVD) foi medida a partir do corte subcostal no eixo longo na extremidade do folheto tricúspide anterior ao final da diástole. A pressão pulmonar foi calculada diretamente pela amostra da insuficiência tricúspide e indiretamente pelo tempo de aceleração (TA) do fluxo pulmonar. O índice de volume do átrio direito (IVAD) foi medido com o volume sistólico final do ventrículo direito pela regra modificada de Simpson. A disfunção diastólica do VD induzida por estresse foi considerada se a razão E/e’ induzida por estresse fosse >6. Todos os parâmetros foram medidos no final da expiração e três vezes durante diferentes ciclos cardíacos.2 ou exato de Fisher. A correlação de Spearman foi usada para avaliar a associação entre os parâmetros TCPE e a razão E/e’ induzida por estresse nos ventrículos esquerdo e direito.Os dados demográficos e clínicos foram apresentados em estatística descritiva. O teste de Kolmogorov-Smirnov foi usado para explorar a normalidade da distribuição. As variáveis contínuas em cada grupo foram expressas como mediana e intervalo interquartil quando os dados não foram normalmente distribuídos, e como média ± desvio-padrão (DP) se a distribuição foi normal. Variáveis categóricas foram apresentadas em proporções. Os dados foram comparados entre pacientes com e sem DDVE, bem como entre pacientes com e sem DDVD. O teste t de Student não pareado foi usado para analisar variáveis contínuas normalmente distribuídas. O teste de Mann-Whitney-U foi usado em outros casos. Variáveis categóricas foram comparadas pelo teste de χEm todos os casos, um valor de p inferior a 0,05 foi considerado significativo, conforme determinado pelas estatísticas do software SPSS® 13.0 .No grupo DPOC, 30% (32/104) dos pacientes apresentaram DDVE grau I em repouso; 14% (15/104) tinham DDVD grau I em repouso e apenas 3% (4/104) tinham tanto DDVE quanto DDVD em repouso. Após o TCPE, a ecocardiografia sob estresse estabeleceu que 64% (67/104) dos indivíduos tinham DDVE induzida por estresse e 78% (82/104) tinham DDVD induzida por estresse. Todos os pacientes com DDVE induzida por estresse também tinham DDVD induzida por estresse. Os dados demográficos e clínicos dos pacientes estão listados na 2 e pulso de O2 mais baixos. Tiveram um desempenho com inclinações de VM/VCO2 significativamente maiores  64% dos pacientes com DPOC não grave e dispneia aos esforços que estão livres de doença cardiovascular clinicamente evidente têm DDVE induzida por estresse; 1) 78% do mesmo grupo de pacientes têm DDVD induzida por estresse; 3) nenhum dos parâmetros TCPE foi correlacionado com a razão E/e’ induzida por estresse no ventrículo esquerdo ou direito. Até onde sabemos, este é o primeiro estudo usando a combinação EES-TCPE em pacientes com DPOC não grave, dispneia aos esforços e livres de doenças cardiovasculares evidentes. Aumento da razão E/e’ induzida por estresse >15 do ventrículo esquerdo foi detectado em 64% deles; elevação induzida por estresse da razão E/e’ >6 no ventrículo direito foi encontrada em 78% dos casos. Não podemos comparar nossos dados com outros estudos de populações de pacientes com DPOC não grave porque a maioria deles relata a incidência de disfunção diastólica em repouso.18 Kaiser et al. também investigaram uma população geral de 87 pacientes com dispneia aos esforços e relataram disfunção diastólica em 9% deles.19Nedeljkovic et al. realizaram EES em uma população de 87 pacientes hipertensos com dispneia aos esforços e função ventricular esquerda normal. Reportaram, em 9,2% dos pacientes, razão por estresse E/e’ >15.21 Rigidez arterial é uma característica da DPOC, independentemente do impacto do tabagismo. O estresse da parede ventricular observado durante a respiração também é relatado como um mecanismo fisiopatológico independente para a remodelação do VE em pacientes com DPOC leve sem patologia cardiovascular evidente.22 Tanto a rigidez arterial quanto o estresse da parede ventricular causam fibrose ventricular difusa em pacientes com DPOC livres de doenças cardiovasculares.24A maior prevalência de disfunção diastólica de estresse que descrevemos em pacientes com DPOC confirma que a própria DPOC é um fator de risco cardiovascular.2 e pulso de O2 mais baixos e apresentam desempenho em inclinações de VM/VCO2 significativamente maiores. Nenhum dos parâmetros TCPE, no entanto, se correlaciona com a razão de estresse E/e’ (nem no VE nem no VD). Esses achados são semelhantes aos relatados na população em geral. Nedeljkovic et al. detectaram menor carga, menor consumo de oxigênio e menor eficiência ventilatória em pacientes hipertensos com dispneia aos esforços e DDVE induzida por estresse.18 Kaiser et al. descreveram aumento da reserva de frequência cardíaca e redução do pulso de oxigênio em uma população geral de pacientes com dispneia aos esforços.19 Guazzi et al. também estabeleceram uma associação entre disfunção diastólica (razão E/e’) e consumo ao pico de oxigênio, eficiência ventilatória e recuperação da frequência cardíaca.25 No grupo de pacientes com patologia cardiovascular evidente e ecocardiografia normal em repouso de Guazzi, a eficiência ventilatória se correlacionou melhor com o pico da razão E/e’ >15. A vantagem clínica da relação VM/VCO2 como melhor preditor da razão por estresse E/e’ também foi confirmada nos pacientes com insuficiência cardíaca diastólica analisados por Nedeljkovic et al.18 Kaiser et al. não apoiam tais conclusões, enfatizando a importância do aumento da reserva da frequência cardíaca e da diminuição no pulso de oxigênio como preditores da razão por estresse E/e’ na população geral de pacientes com dispneia aos esforços e livres de doença cardiovascular evidente.19Em nosso estudo, pacientes com disfunção diastólica induzida por estresse (ambos DDVE e DDVD) atingem carga, VO9 De acordo com nossos resultados, em pacientes com DPOC, esses não são parâmetros clínicos confiáveis que podem servir como preditores independentes de anormalidade cardiovascular e, portanto, não são aplicáveis no algoritmo de diagnóstico de disfunção diastólica mascarada.Parece que os parâmetros TCPE podem ajudar no diagnóstico diferencial de dispneia na população em geral, bem como em pacientes com patologia cardiovascular diagnosticada.6 Como nenhum dos parâmetros do teste de esforço cardiopulmonar provou ser preditivo de DDVE/DDVD induzida por estresse, a ecocardiografia de estresse tem grande relevância clínica para um diagnóstico preciso de patologia cardíaca e respiratória em pacientes com DPOC não graves e dispneia aos esforços.Nossos achados corroboram a presença de comprometimento funcional em pacientes com DPOC não grave com dispneia aos esforços e livres de doença cardiovascular evidente. O Doppler tecidual durante o exercício mostra a complexa interação coração-pulmão e as alterações induzidas pelo esforço, que aumentam os comprometimentos funcionais cardíacos que podem não ser evidentes em repouso. Nossos achados apoiam as recomendações atuais de EES-TCPE como uma ferramenta para detecção precoce de ICFEP.O estudo teve as seguintes limitações: 1) tamanho de amostra relativamente pequeno; 2) falta de pletismografia corporal e medida da capacidade de difusão, que são informativos para uma avaliação adequada da dispneia; 3) pacientes com DPOC apresentam oscilações de pressão aumentada durante o ciclo respiratório, e a medição foi realizada ao final da expiração, o que pode influenciar os resultados; 4) as medições foram feitas no início do período de recuperação (aproximadamente dois minutos) após o exercício limitado por sintomas. A linha do tempo das mudanças das pressões pulmonar e intratorácica durante o breve intervalo entre o pico do exercício e sua medida no início da recuperação não é bem conhecida e poderia, portanto, ser subestimada.Há uma alta prevalência de disfunção diastólica induzida por estresse em pacientes com DPOC não grave com dispneia aos esforços, sem doença cardiovascular evidente. Nenhum dos parâmetros do TCPE se correlaciona com a razão E/e’ induzida por estresse. Portanto, a realização do EES-TCPE é necessária para a detecção precoce e o manejo adequado da ICFEP mascarada nesta população. 2 Arterial stiffness is present even in mild COPD patients free of cardiovascular diseases. It is an independent cardiovascular risk factor that contributes for the development of diastolic dysfunction.3 Dyspnea and exercise intolerance are common symptoms for both COPD and diastolic dysfunction.4 Recent studies with large patient cohorts have identified a cardiovascular phenotype in COPD patients who present with a different clinical course and prognosis.5 Early diagnosis and management is, therefore, very important from the clinical point of view.Cardiovascular abnormalities are common in chronic obstructive pulmonary disease (COPD).9 The combination of exercise stress-echocardiography (ESE) and CPET is a reliable approach to identify patients with masked heart failure with preserved ejection fraction (HFpEF). Moreover, the results from invasive measurements are comparable to data obtained with non-invasive studies during ESE.10Cardiopulmonary exercise testing (CPET) may distinguish cardiac and respiratory dyspnea or diminished physical activity.’).The aims of our study were: 1) to detect the frequency of subclinical left ventricular (LV) and right ventricular (RV) diastolic dysfunction in non-severe COPD patients free of cardiovascular disease; 2) to establish a correlation between cardiopulmonary exercise and echocardiographic parameters for diastolic dysfunction (E/e1>50%). All subjects had exertional dyspnea, but a total of 104 patients  were considered eligible, assuming the exclusion criteria. The recruitment period was between May 2017 and April 2018, and was approved by the local Ethics Committee (protocol 5/12.03.2018). All participants signed the informed consent form before the study initiation.This was a retrospective study conducted with 224 clinically stable outpatients diagnosed with COPD at the University Hospital for Respiratory Diseases “St. Sophia”, Sofia. Only 163 of them met the inclusion criteria for non-severe COPD – forced expiratory volume in the first second higher than 50% (FEVThe following exclusion criteria were considered: 1) left ventricular ejection fraction (LVEF) <50%; 2) left ventricular diastolic dysfunction at rest higher than first grade; 3) echocardiographic findings suggesting pulmonary hypertension  jet maximum velocity >2.8 m/s; 4) valvular heart disease; 5) documented cardiomyopathy; 6) severe uncontrolled hypertension (systolic blood pressure >180 mmHg and diastolic blood pressure >90 mmHg); 7) atrial fibrillation or malignant ventricular arrhythmia; 8) ischemic heart disease; 9) anemia; 10) diabetes mellitus; 11) cancer; 12) chronic kidney disease (CKD); 13) recent chest or abdominal surgery; 14) recent exacerbation (over the last three months); 15) recent change (over the last three months) in medical therapy.11Only patients with mild to moderate airway obstruction (FEV1 >50%) were selected.All subjects underwent preliminary clinical examination including chest X-ray, spirometry, electrocardiography, echocardiography. Patients eligible for the study performed spirometry and an exercise stress test. They were performed on Vyntus, Cardiopulmonary exercise testing , in accordance with the European Respiratory Society (ERS) guidelines.6 After two minutes of unloaded pedaling (rest phase 0W), a three-minute warm-up phase (20W) followed. The test phase included 20W/2min load increments. Patients were instructed to pedal with 60 rotations per minute.A continuous ramp protocol was applied according to guidelines.2 was expressed as the highest 30-second average value, obtained during the last stage of the exercise test. The peak values of VO2 are expressed as -O2 ml/kg/min. Ventilatory efficiency (VE/VCO2) was measured by the V-slope method. Peak respiratory exchange ratio (pRER) was the highest 30-second value averaged in the last stage of the test. RER >1.10 at the end of the ESE-CPET test was considered as achievement of maximal effort.Expiratory gases were collected on a breath-by-breath basis. Peak VO13 Apical four-chamber views were used to measure chamber volumes based on Simpson’s modified rule and LV ejection fraction was considered preserved if >50%. Doppler tissue echocardiography (DTE) analysis was performed in the septal-lateral dimension of mitral annulus, and lateral dimension of tricuspid annulus to assess myocardial systolic (S) and diastolic  waves of LV and RV. The E’ value was used as average of medial and lateral measurements. Peak E/e’ ratio >15 was considered a marker for stress-induced left ventricular diastolic dysfunction.M-mode, two-dimensional and Doppler echocardiography were performed.14Right ventricular systolic function was assessed using tricuspid annular plane systolic excursion (TAPSE) and tissue Doppler S peak velocity. Right ventricular wall thickness (RVWT) was measured from the subcostal long-axis view at the tip of the anterior tricuspid leaflet in end-diastole. Pulmonary pressure was calculated directly by sampling the tricuspid insufficiency and indirectly by the acceleration time (AT) on pulmonary flow. Right atrium volume index (RAVI) was measured with the right ventricular end-systolic volume by the Simpson’s modified rule. Stress-induced RV diastolic dysfunction was considered if stress-induced E/e’ ratio >6. All parameters were measured at end-expiration and in triplicate during different heart cycles.2 test or the Fisher’s exact test. The Spearman’s rank correlation was used to assess the association between CPET parameters and stress-induced E/e’ ratio for the left and right ventricles.Demographic and clinical data were presented with descriptive statistics. The Kolmogorov-Smirnov test was used to explore the normality of distribution. Continuous variables in each group of subjects were expressed as median and interquartile range when data was not normally distributed and as mean ± standard deviation (SD) if normal distribution was observed. Categorical variables were presented as proportions. Data were compared between patients with and without LVDD, as well as between patients with and without RVDD. The unpaired Student’s t test was used to analyze normally distributed continuous variables. The Mann-Whitney-U test was used in other cases. Categorical variables were compared by the χIn all cases, a p value of less than 0.05 was considered significant, as determined with SPSS® 13.0 Software  statistics.In the COPD group, 30% (32/104) of patients had grade I LVDD at rest; 14% (15/104) had grade I RVDD at rest and only 3% (4/104) had both RV and LVDD at rest. After CPET, the stress-echocardiography established that 64% (67/104) of the subjects had stress-induced LVDD, and 78% (82/104) had stress-induced RVDD. All patients with stress-induced LVDD also had stress-induced RVDD. The demographic and clinical data of patients are listed in 2 and O2-pulse. They performed with significantly higher VE/VCO2 slopes  64% of the patients with non-severe COPD and exertional dyspnea who are free of clinically evident cardiovascular disease have stress-induced LVDD; 1) 78% of the same group of patients have stress-induced RVDD; 3) none of the CPET parameters was correlated with stress-induced E/e’ ratio either in the left or the right ventricle. To our knowledge, this is the first study using combined ESE-CPET in non-severe COPD patients with exertional dyspnea and free of overt cardiovascular diseases. Stress-induced increase of E/e’ ratio >15 of the left ventricle was detected in 64% of them; stress-induced elevation of E/e’ ratio >6 of the right ventricle was met in 78% of cases. We cannot compare our data to other studies of non-severe COPD patient populations because most of them report on the incidence of diastolic dysfunction at rest+18 Kaiser et al. also investigated a general population of 87 patients with exertional dyspnea and reported diastolic dysfunction in 9% of them.19Nedeljkovic et al. performed ESE in a population of 87 hypertensive patients with exertional dyspnea and normal left ventricular function. They found in 9.2% of the patients a stress ratio E/e’ >15.21Arterial stiffness is a feature of COPD, regardless of the smoking burden. The ventricular wall stress seen during respiration is also reported as an independent pathophysiological mechanism for LV remodeling in mild COPD patients without overt cardiovascular pathology.22 Both arterial stiffness and ventricular wall stress cause diffuse LV fibrosis in COPD patients free of cardiovascular diseases.24The higher prevalence of stress diastolic dysfunction that we describe in COPD patients confirms that COPD itself is a cardiovascular risk factor.2 and O2-pulse and perform with significantly higher VE/VCO2 slopes. None of the CPET parameters, however, correlates with stress E/e’ ratio (neither in LV nor RV). These findings are similar to what have been reported in the general population. Nedeljkovic et al. detected lower load, lower oxygen consumption and lower ventilatory efficiency in hypertensive patients with exertional dyspnea and stress-induced LVDD.18 Kaiser et al. described increased heart rate reserve and reduced oxygen pulse in a general population of patients with exertional dyspnea.19 Guazzi et al. also established an association between diastolic dysfunction (E/e’ ratio) and peak oxygen consumption, ventilatory efficiency and heart rate recovery.25 In Guazzi’s group of patients with overt cardiovascular pathology and normal echocardiography at rest, ventilatory efficiency correlated best to peak E/e’ ratio>15. The clinical advantage of VE/VCO2 ratio as the best predictor of stress E/e’ ratio was also confirmed in the diastolic heart failure patients analyzed by Nedeljkovic et al.18 Kaiser et al. do not support such conclusions, emphasizing the importance of the increased heart rate reserve and diminished oxygen pulse as predictors of stress E/e’ ratio in the general population of patients with exertional dyspnea and free of overt cardiovascular disease.19In our study, patients with stress-induced diastolic dysfunction (both LVDD and RVDD) achieve lower load, VO9 According to our results, in COPD patients, these are not reliable clinical parameters that may serve as independent predictors for cardiovascular abnormality and, thus, are not applicable in the diagnostic algorithm of masked diastolic dysfunction.It seems that the CPET parameters may help in the differential diagnosis of dyspnea in the general population, as well as in patients with diagnosed cardiovascular pathology.6As none of the cardiopulmonary exercise testing parameters proved to be predictive of stress-induced LVDD/RVDD, stress echocardiography has great clinical relevance for an accurate diagnosis of cardiac and respiratory pathology in non-severe COPD patients with exertional dyspnea.Our findings support the presence of functional impairment in non-severe COPD patients with exertional dyspnea and free of overt cardiovascular disease. The performance of tissue Doppler imaging during exercise demonstrates the complex heart-lung interaction and the effort-induced changes, which increase cardiac functional impairments that may not be evident at rest. Our findings support the current recommendations for ESE-CPET as a tool for early detection of HFpEF.The study had the following limitations: 1) relatively small sample size; 2) lack of body plethysmography and diffusion capacity measurement, which are informative for the proper assessment of dyspnea; 3) COPD patients experience enhanced pressure swings during the respiratory cycle, and the measurement was performed at the end of expiration, which may influence results; 4) measurements were made in early recovery period (approximately 2 min) after symptom-limited exercise. The timeline of changes of pulmonary and intrathoracic pressures during the brief interval between peak exercise and their measurement in early recovery is not well known and it could, therefore, be underestimated.There is a high prevalence of stress-induced diastolic dysfunction in non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease. None of the CPET parameters correlates with the stress-induced E/e’ ratio. Therefore, the performance of ESE-CPET is needed for the early detection and proper management of masked HFpEF in this population.


Many previous studies reported the negative effects of right ventricular (RV) pacing on the left ventricular (LV) structure and ejection fraction. Studying pacing hemodynamics is essential to understand these detrimental effects. In this study, we tried to understand RV pacing effects on LV volumes and function using advanced tools like 3D echo and global longitudinal strain (GLS). This was a prospective study of 175 consecutive patients (LVEF>50%) presented permanent pacing. Of 175 patients, only 50 patients met study criteria, divided into two groups . LV volumes and function were assessed by full-volume 3D echocardiography and GLS before pacing, at 1-week and 6-month post-pacing. Cardiac output (COP) was calculated by pulsed wave Doppler method and 3D echo.Doppler method results were similar to 3D echo in calculating SV and COP. At 1-week post pacing, both groups showed a significant decrease in SV due to a drop in EDV while ESV did not change significantly. Despite the drop in SV, there was a significant increase in cardiac output (COP) due to achieving higher heart rates post-pacing. There was a significant drop in EF and GLS in both groups.At 6 months, SV continued to decrease with a corresponding decrease in COP and LVEF. This drop in SV was due to a significant increase in ESV while EDV did not show a significant change at a 6-month follow-up. Also, the drop EF and GLS became more significant.There were no significant differences between both groups regarding the changes in LV volumes , LVEF or GLS throughout the study . However, dual-chamber pacing group provided higher heart rates and as a result higher COP than the single-chamber group.RV pacing led to a significant drop in LV COP, ejection fraction (EF), and GLS over short- and long-term duration. Dual chamber pacing provided higher COP than a single chamber pacing. This was due to tracking the S. A node with pacing at higher heart rates not due to an increase in SV and preserving atrioventricular synchrony. Both Doppler method and 3D echo can be used to calculate SV and COP.The online version contains supplementary material available at 10.1186/s43044-021-00138-9. Cardiac pacing is the established treatment of the heart block since more than 50 years . At firsAs a result, dual-chamber pacing, as compared with single-chamber ventricular pacing, improves hemodynamic function –6, but tOn the other hand, a number of randomized studies suggested no significant differences between single-chamber and dual-chamber pacing in the rates of atrial fibrillation, heart failure, or a composite of stroke, ischemic attack or death –12. In tThe study was approved by our faculty of medicine ethics committee. All patients provided written informed consent.Patient recruitment started from October 2017 to August 2018. During this period, 175 consecutive patients presented to our university hospitals for device implantation.The exclusion criteria included the presence of more than mild valvular heart disease, left ventricular ejection fraction less than 50%, presence of ischemic heart disease, and recent cardiac surgery during the last 3 months before enrollment. Patients with poor echo windows, patients with slow atrial fibrillation or other types of arrhythmia that can affect stroke volume measurement, debilitated or cancer patients with expected survival less than 1 year and patients with previously implanted devices were excluded. From 175 patients, 124 patients were excluded. Sixty-five patients were presented with reduced LV systolic function for cardiac resynchronization therapy. Sixteen patients were assigned for ICD devices as a primary or secondary prevention with no indication for permanent pacing. Twenty-two patients had previously implanted devices at elective replacement period and were scheduled for battery replacement. Seven patients were subjected to reoperation due to device related complications (4 with twiddler syndrome and 3 for device extraction due to bloodstream or device-related infection). Eight patients presented with slow atrial fibrillation or SSS. Two patients had poor echo views, and 4 patients had significant valvular heart disease. One patient died before the second follow-up. The remaining 50 patients were distributed to have single chamber (27 patients) or dual chamber pacemaker (23 patients).Patient’s demographic data and indications for pacing were collected and revised 24 h before pacing. Patient’s age ranged from 12 to 97 years with mean age of 63.12 ± 16.85 years. According to gender, 27 patients were males (54%) and 23 were females (46%). All the patients had structurally normal heart confirmed by echocardiography  were done according to the standard techniques. Patients were told to hold their breath during acquisition, and foreshortening was avoided. GLS was calculated for each of the three apical view, and then, mean GLS was calculated automatically.Implantation was performed according to the operator’s preference. Being easily accessible, more stable and non-inferior to RV septal pacing , 14, RV t (parametric) or Wilcoxon signed-rank (non-parametric) tests as appropriate. p values of less than 0.05 were regarded as significant.The database was maintained and analyzed by an independent data-management group. To assess the distribution of the data derived from this study, we calculated the standardized skewness and kurtosis of each of the variables. Normally distributed values were expressed as mean and skewed values as the median (interquartile range). Paired two-tailed group comparisons were made with Student’s It was found that Doppler method was not inferior to 3D echo in calculating SV and COP Table . There wp value < 0.001). COP is the result of multiplying SV by HR. Consequently, dual-chamber pacemakers provided higher COP than single-chamber devices . Both HR and COP showed a significant increase post-pacing. However, at post-pacing visits, dual-chamber group achieved higher HR by tracing the patients’ intrinsic heart rate . Also, the decrease in SV from 1 week to 6 months was significant in single and dual chamber groups. . GLS showed a significant reduction post-pacing in both groups . Again, the reduction in GLS from 1 week to 6 months was significant in single and dual chamber groups , without affecting LV dimensions.In 2006, n et al.  comparedLiu et al. [P=0.07) and LVEF  during RV pacing.In 2008, u et al.  studied Delgado et al. [P<0.001).In 2009, o et al.  studied Few published data were found on the acute effects of RV apical pacing on LV volumes and function. Our results matched with the previously published studies:During recent years, many studies reported negative effects of RV pacing on cardiac structure and function, with detrimental clinical outcomes such as atrial fibrillation, heart failure, and death –26. ThesAt second follow-up, pacing led to an additional drop in EF. The main cause was pacing induced remodeling of LV structure resulting in expansion of ESV. Also, GLS dropped significantly in comparison to the measured values at 1 week. These findings signified the long-term negative impacts of RV pacing on LV function. Our study was not the first one to report a decline in LV function as a result of chronic RV pacing.In a 6-month study of 36 patients without structural heart disease and LVEF greater than 45%, presented for permanent pacing, significant drops in LVEF were noted in 12 patients. A significant decrease in LV global longitudinal strain was noted in 23 patients . Our stuThe multicenter, randomized UK-PACE Trial  includedThe DAVID Trial  and a suDelgado et al. [P<0.001) together with an impairment in LV global longitudinal strain  and in LV twist . The study concluded that RV apical pacing induced acute LV dyssynchrony.In 2009, o et al.  studied p<0.001). In regression analysis, lower LV global longitudinal strain was the only independent predictor for LV dyssynchrony . The study concluded that patients with lower GLS value could be at risk of cardiomyopathy and need more close monitoring [A recent study conducted in 2017 evaluated the value of GLS as a predictor for pacing induced LV dyssynchrony. In 93 patients followed for 5 years, cardiomyopathy developed more prevalently in dyssynchrony group  synchrony, DDD/R did not reduce pacing-related cardiomyopathy and was not superior to VVI/R mode.RV pacing led to detrimental effects on SV, COP, EF, and GLS over short- and long-term duration. Dual-chamber pacing provided higher COP than a single-chamber pacing. This was due to tracking the S.A node with pacing at higher heart rates not due to an increase in SV, preserving atrioventricular synchrony or the atrial kick. Both Doppler method and 3D echo can be used to calculate SV and COP.Additional file 1. SV by PW, 3D.Additional file 2. 3D Echo.Additional file 3. GLS.


Heart failure patients presenting with iron deficiency can benefit from systemic iron supplementation; however, there is the potential for iron overload to occur, which can seriously damage the heart. Therefore, myocardial iron (M-Iron) content should be precisely balanced, especially in already failing hearts. Unfortunately, the assessment of M-Iron via repeated heart biopsies or magnetic resonance imaging is unrealistic, and alternative serum markers must be found. This study is aimed at assessing M-Iron in patients with advanced heart failure (HF) and its association with a range of serum markers of iron metabolism. n = 11) were used as control/reference tissue. Concentrations of serum iron-related proteins (FR and sTfR1) were assessed.  Left ventricle (LV) myocardial biopsies and serum samples were collected from 33 consecutive HF patients  with LV dysfunction (LV ejection fraction 22 (11) %; NT-proBNP 5464 (3308) pg/ml) during heart transplantation. Myocardial ferritin (M-FR) and soluble transferrin receptor (M-sTfR1) were assessed by ELISA, and M-Iron was determined by Instrumental Neutron Activation Analysis in LV biopsies. Nonfailing hearts . Of the serum markers, sTfR1/logFR correlated with  and predicted  LV M-Iron. LV M-Iron load (μg/g) can be calculated using the following formula: 210.24–22.869 × sTfR1/logFR.  LV M-Iron load was reduced in all HF patients and negatively associated with M-FR ( The sTfR1/logFR ratio can be used to predict LV M-Iron levels. Therefore, serum FR and sTfR1 levels could be used to indirectly assess LV M-Iron, thereby increasing the safety of iron repletion therapy in HF patients. Iron dee damage –12. TherMyocardial iron (M-Iron) metabolism has also been shown to be strongly related to left ventricle (LV) remodeling in HF , 14. IndThis study is aimed at assessing M-Iron load in the failing LV in relation to serum markers of iron metabolism to develop an indirect method of M-Iron assessment without performing a heart biopsy. This noninvasive assessment should increase the safety of iron supplementation in HF patients.The protocol was approved by the Local Ethics Committee. Each patient participating in the study signed an informed consent form after a detailed explanation of the study principles. The study group comprised 33 consecutive patients referred to orthotopic heart transplantation (OHT). Myocardial studies were performed in failing ventricular myocardium obtained during transplantation.All clinical assessments and blood sampling were performed just before OHT.Two-dimensional, M-mode, and color Doppler transthoracic echocardiography was performed at rest according to the recommendations of the American Society of Echocardiography. Right heart catheterization, hemodynamic and cardiac output measurements, and resistance calculations were performed just before OHT.μl), hematocrit (Hct: 42–52/37–47%), mean corpuscular volume (MCV: d80–99 fl), hemoglobin (Hb: 14–18/12–16 g/dl), and mean corpuscular hemoglobin (MCH: 27–32 pg).Blood counts were determined with an automatic counter (Sysmex K4500), as follows: red blood cell (RBC) count , transferrin (200–360 mg/dl), transferrin saturation , total iron-binding capacity , and unsaturated iron-binding capacity . The COBAS Integra® 800 System (Roche Diagnostic) was used to evaluate soluble transferrin receptor (sTfR: 2.2–5.0/1.9–4.4 mg/l), high-sensitivity C-reactive protein , sodium (136–145 mmol/l), and creatinine (62–106/44–80 μmol/l). The ARCHITECT® Immunochemistry Diagnostics Platform (Abbott Laboratories) was used to determine ferritin . Chemiluminescent IMMULITE 2000  was used to measure erythropoietin . The Cobas e411R analyzer (Roche Diagnostic) was used to determine N-terminal pro-B-type natriuretic peptide . Tumor Necrosis Factor-alpha (TNFα) levels were assayed by an enzyme-linked immunosorbent assay  according to the manufacturer's instructions .Body iron status and biochemical assessment were evaluated in serum using the Clinical Chemistry System Olympus 680 (Olympus Life Science) as follows: serum iron ∗∗ .The estimated total dose required for iron repletion (TIRD) was assessed by the Ganzoni formula: TIRD (mg) = body weight (kg) ×  × 2.4Tissue samples of the LV free wall were taken at the time of explantation , rinsed immediately, blotted dry, frozen in liquid nitrogen, and kept at -80°C until use.In total, 80–100 mg of cardiac tissue was homogenized using an Ultra-Turrax T25 homogenizer in buffer with a Complete Protease Inhibitor Cocktail. Homogenate was filtered through two layers of gauze and centrifuged at 10,000 × g for 10 min. The supernatant was collected, portioned, rapid frozen in liquid nitrogen, and stored at -75°C. The total protein concentration was determined by the Bradford method. M-FR  and M-sTfR1  were assayed by ELISA according to the manufacturer's instructions.14 cm−2 s−1 for 50 min in a nuclear reactor MARIA . After three weeks of cooling, the gamma-ray emission of the samples and standards was measured with the GENIE-2000 Canberra Gamma Spectrometry System and the GENIE 2000 software .M-Iron was assayed by Instrumental Neutron Activation Analysis (INAA). In brief, frozen samples were lyophilized , weighed, and packaged in HDPE snap-cap capsules . The certified reference material NIST 1577c Bovine Liver , US) was used for quality control. Samples and standards were irradiated at the neutron flux of 10Data are expressed as means (SD) or as medians (IQR) for data that were not normally distributed. The test for normality for each analyzed parameter was performed using the Shapiro-Wilk test. Pearson correlation matrices were used to establish univariate correlations among M-Iron and other parameters. A stepwise multiple regression analysis was employed to assess the strongest model of independent predictors of M-Iron.α 15.8 (9.7) pg/ml; hsCRP 0.72 (0.3) mg/dl) activation , with a mean age of 48 years, who were referred for OHT. The study group presented with LV dilatation or dysfunction (LVESV 189 (95) ml; LVEDV 245 (83) ml; LVEF 22 (11) %), RV enlargement (RVD 32 (10) mm), pulmonary hypertension (PVR 3.36 (1.2) W.u.), and significant neurohumoral (NT-proBNP 5464 (3308) pg/ml) and proinflammatory  = 210.24–22.869 × sTfR1/logFR.Based on our calculations and obtained correlations after the mathematical transformation, the formula for LV M-Iron calculations is LV M‐Iron load  is common in chronic diseases, and iv iron supplementation is now often used in cardiology, oncology, hematology, and nephrology patients , 19, 20.<100 μg/l or between 100 and 299 μg/l when TSAT is <20% [Bone marrow biopsy assessment is the most accurate method to define ID  , 22. How is <20% , 24. Nev is <20% .Regarding M-Iron, there is a general agreement that the M-Iron load is reduced in a failing LV –15. MoreOnly a few studies have evaluated changes in the expression of M-TfR1, the main protein responsible for iron acquisition, albeit with conflicting results. While Maeder et al. reported a reduction of M-TfR1 expression at the mRNA level in HF , we wereAlthough there are undoubtedly links between M-Iron, M-FR, and M-TfR1 at the cellular level in the failing myocardium, our work proves that traditionally used clinical serum markers for body iron stores, such as TSAT and FR, do not reflect the actual M-Iron status. Serum FR has been commonly used as a clinical biomarker of ID since the early 1970s . FR is pAs the currently used serum markers are not satisfactory, and the direct assessment of M-Iron content by heart biopsies or frequent magnetic resonance imaging examination is not realistic, alternative serum markers must be found for the reliable assessment of M-Iron content. Our results validated the parameters commonly used for iron load assessment and demonstrated that the M-iron load can be assessed more accurately based on serum sTfR1, particularly by calculating the sTfR1/logFR ratio. Circulating sTfR1 is produced by the proteolytic cleavage in direct proportion to the cellular receptor content . sTfR1 lIn the HF population, iron repletion and the total iron repletion dose (TIRD) required for supplementation for an individual ID patient is usually calculated using the Ganzoni formula and relies on the subject's weight and Hb value . Howeverμg/g) = 210.24–22.869 × sTfR1/logFR. Therefore, when referring to the LV M-Iron load in HF and non-HF patients, we postulate that iv iron repletion therapy may be additionally tailored by the noninvasive M-Iron calculation based on the above formula. This formula allows the LV M-Iron content to be approximated at each stage of iv iron supplementation in a noninvasive way.Iron repletion therapy is usually tailored based on the presence of ID criteria  , 37. We There are some limitations to our study. In particular, the presented work is based on a limited, but representative, homogeneous population of patients with advanced HF (33 patients) subjected to heart transplantation. Despite this, the population size is comparable to the size of the population on which the fundamental formula for iron deficiency calculations was established by Ganzoni (30 patients). Nonetheless, prospective longitudinal studies involving follow-up measurements of proposed parameters are needed for improved data modeling.In summary, among the commonly used serum markers for iron turnover assessment, only the sTfR1/logFR ratio is an independent predictor of LV M-Iron. In this study, we present a formula that enables the indirect assessment of LV M-Iron, which will help increase the safety of iron repletion therapy in HF patients.


Cirrhotic cardiomyopathy was first described in 1969 by Regan TJ et al. and was found in all kinds of liver cirrhosis since 1990. Nevertheless the disease is still not well understood due to the hyperdynamic LV function, the lack of reliable diagnostic tools as well as multimorbidity of patients with end stage liver disease. However there is evidence for a reduced cardiac response to stress factors, QT-prolongation as well as myocardial fibrosis, subendocardial edema and vacuolization of myocytes.The aim of this study was to further investigate the evidence of cirrhotic cardiomyopathy in patients with end stage liver disease by cardiac MRI.We examined 20 patients  who are/were listed for liver transplantation  because of alcoholic liver cirrhosis on a 1.5 T Philips Achieva scanner using a 5-element phased array cardiac synergy coil in 2007. Multiple short axes (SAX) cine images using a SSFP sequence with parallel imaging were acquired for the assessment of left ventricular ejection fraction (LVEF %) followed by a standardized high-dose dobutamine stress protocol up to 40 μg per kilogram of body weight per minute. A 3D FFE SAX multi-slice inversion recovery sequence 10 minutes post-Gd ) was employed for the measurement of LE. TNT and NT-proBNP were measured according to clinical routine procedures .All patients showed normal to hyperdynamic LVEF at rest 71,3 ± 8%) as described before with other imaging methods and no wall motion abnormalities at rest or during dobutamine stress. However relevant LE (27,4 ± 17,4% of myocardial mass (see figure ,3 ± 8% aThis is the first description of myocardial delayed contrast enhancement in patients with end stage liver disease. We assume that these findings might be of diagnostic and prognostic value and might be helpful to detect patients at risk for cardiac complications on the waiting list for liver transplantation. However further studies with bigger sample sizes have to be done to fortify our results.


We aimed to identify mechanical and pharmacological revascularization strategies correlated with the index of microcirculatory resistance (IMR) in ST-elevation myocardial infarction (STEMI) patients.  Microvascular dysfunction (MVD) after STEMI is correlated with infarct size and poor long-term prognosis, and the IMR is a useful analytical method for the quantitative assessment of MVD. However, therapeutic strategies that can reliably reduce MVD remain uncertain. th percentile of IMR in enrolled patients (IMR > 30.9 IU).  Patients with STEMI who underwent primary percutaneous coronary intervention (PCI) were enrolled. The IMR was measured with a pressure sensor/thermistor-tipped guidewire immediately after primary PCI. High IMR was defined as values ≥66P=0.006), delayed hospitalization from symptom onset (P=0.004), peak troponin-I level (P=0.042), and multivessel disease (P=0.003) were associated with high IMR. Achieving final thrombolysis in myocardial infarction myocardial perfusion grade 3 tended to be associated with low IMR (P=0.119), whereas the presence of distal embolization was significantly associated with high IMR (P=0.034). In terms of therapeutic strategies that involved adjusting clinical and angiographic factors associated with IMR, preloading of third-generation P2Y12 inhibitors correlated with reducing IMR value . Mechanical therapeutic strategies including stent diameter/length, preballoon dilatation, direct stenting, and thrombectomy were not associated with low IMR value , and postballoon dilatation was associated with high IMR .  A total of 160 STEMI patients were analyzed (high IMR = 54 patients). Clinical factors for Killip class ( In our study, mechanical strategies were suboptimal in achieving myocardial salvage. Preloading of third-generation P2Y12 inhibitors revealed decreased IMR value, indicative of MVD prevention. ST-elevation myocardial infarction (STEMI) is usually caused by complete occlusion of a major epicardial coronary artery and results in myocardial ischemia and cell death. Early reopening of the culprit artery by primary percutaneous coronary intervention (PCI) is now considered as the cornerstone of the treatment –3. HowevThe index of microcirculatory resistance (IMR) can provide a quantitative assessment of the microvascular function of epicardial stenosis and hemodynamic condition independently. IMR is considered an independent, powerful predictor of microvascular damage in STEMI –15. ReceThrough imaging tools or invasive coronary physiological indices, many studies have attempted to prove the therapeutic strategies of mechanical and pharmacological revascularization that can reduce microvascular damage from myocardial infarction. However, there are no definitive treatments for myocardial infarction that can reliably reduce microvascular damage, and some current therapeutic strategies remain controversial , 16–18.Therefore, we aimed to identify mechanical and pharmacological revascularization strategies that prevent MVD in patients with STEMI using IMR that can assess microvascular integrity with primary PCI.We retrospectively reviewed consecutive patients with STEMI who underwent primary PCI with coronary physiological measurements between May 2009 and June 2016 at the clinic of a tertiary referral center .J point in two contiguous leads of ≥2 mm (0.2 mV) in men or ≥ 1.5 mm (0.15 mV) in women in leads V2∼3 and/or of ≥1 mm (0.1 mV) in other contiguous chest leads of the limb leads ) min versus 95.0  versus 0.2 [0.2–0.3], P < 0.001, respectively). The overall value of FFR was similar between the two groups, whereas CFR was lower in the High IMR group . The overall median IMR was 22.4 [13.9–35.0] U.In physiological assessment, there were significant differences in resting Tmn and hyperemic Tmn . CV death occurred in 3 (2.0%) patients who were included only in the High IMR group (P=0.038). Other events including hospitalization for HF, TLR, stent thrombosis, nonfatal MI, stroke, and major bleeding were comparable  patients and were comparable between the two groups . Forty-two patients (26.2%) underwent direct stenting and 75 patients (46.9%) underwent aspiration thrombectomy. Thirty-one patients (19.4%) underwent a combination of aspiration thrombectomy with GP IIb/IIIa inhibitors. All mechanical therapeutic strategies showed no significant difference between the two groups.Mechanical and pharmacological treatment strategies were accessed in the study population . All patP=0.023). The GP IIb/IIIa inhibitor was more frequently used in the High IMR group than in the Low IMR group . In terms of morphine use, both groups showed almost equal proportions .All patients received preloading with 300 mg of aspirin. The High IMR group showed a higher incidence of clopidogrel use than third-generation P2Y12 inhibitors . Longer stent length and postballoon dilatation were associated with higher IMR value . Preballoon dilatation, direct stenting, and thrombectomy showed no significant association with IMR value. In pharmacological strategies, the loading of third-generation P2Y12 inhibitors was significantly associated with low IMR value . The use of morphine and GP IIb/IIIa inhibitor was not associated with low IMR value.We analyzed each therapeutic strategy for the association of IMR value using linear regression analysis . In mechβ = −9.39, P=0.018 and β = −10.69, P < 0.001, respectively). Postballoon dilatation and the use of GP IIb/IIIa inhibitor were positively correlated with IMR value .In multiple regression analysis for therapeutic strategies using stepwise regression, stent diameter and loading of third-generation P2Y12 inhibitors were negatively correlated with IMR value . A comparison of IMR according to therapeutic strategies is shown in We analyzed each therapeutic strategy that was significantly associated with IMR value, adjusting for age, sex, and parameters for the previous multiple analysis model in The main objective of this study was to determine the therapeutic strategy to reduce MVD in patients with STEMI. The major findings of this study were as follows. (1) Higher Killip class, higher peak troponin-I level, presence of multivessel disease, distal embolization, and delayed reperfusion time were associated with higher IMR value. This finding was consistent with those in previous studies. (2) The mechanical therapeutic strategy had no significant association with lower IMR value. (3) In pharmacological strategies, the preloading of third-generation P2Y12 inhibitors showed a significant association with lower IMR value.It has been reported that the burden of ischemic myocardia is a crucial factor in determining the occurrence of MVD –9. The eMany previous articles show that the IMR provides coronary microcirculation and is independently predictive of LV function and infarct volume and microvascular damage after STEMI , 23, 24.Previous studies have reported that the occurrence of heart failure (higher Killip class), multivessel disease, and a longer duration from symptom onset was associated with poor prognosis , 25. AlsTMPG reflected the degree of impaired myocardial perfusion. Impaired TMPG has been associated with a greater coronary thrombus burden, larger infarct size, and poorer salvage indices , 26. AchReducing periprocedural myocardial injury and enhancing myocardial salvage during primary PCI in patients with STEMI have been a major concern for treatment strategies. Recent studies have shown that distal embolization occurs in 11% of patients STEMI treated by conventional primary PCI and that occurrence increases the risk of heart failure . TherefoVarious studies have been conducted on the effectiveness of aspiration thrombectomy. However, these promising results did not lead to clinical benefit in the previous randomized trials , 30. ThuAlthough recent meta-analysis showed that intracoronary GP IIb/IIIa inhibitors might be reasonable as bailout therapy in high-risk patients with STEMI, there is no evidence that routine use during primary PCI could reduce myocardial ischemic size . The useA previous cohort study showed that intravenous morphine infusion had a positive effect on preventing myocardial reperfusion injury. They suggested that morphine inhibits the opening of mitochondrial permeability transition pores (mPTP) mediated by the activation of delta-opioid receptors. Opioid receptor activation-triggered postconditioning may protect the myocardial injury by targeting mPTP . HoweverThird-generation P2Y12 inhibitors, prasugrel and ticagrelor, are recommended based on improved clinical outcomes and more potent platelet inhibition compared with clopidogrel in acute coronary syndrome (ACS) . When coOur data did not show any beneficial effect of mechanical strategies on lowering IMR value. Although the larger stent diameter and shorter stent size tend to be associated with lower IMR values in multiple regression analyses which suggested that securing the maximal stent lumen and minimizing the stent length are important for myocardial salvage, our findings suggested that conventional mechanical procedures did not reduce distal embolization effectively. However, as the interventional approach is driven by the operator's decision depending on the nature of the culprit lesion, our mechanical therapeutic strategy cannot be generalized. Thus, selection bias dependent on the interventionist may be reflected in the establishment of treatment strategies, and these variables may play a role as confounders. Moreover, because of data from a relatively small number of patients and a single referral tertiary institute were used, our study participants may be a skewed and selected population based on disease severity and comorbidities, rather than representing the general population. In our study, IMR alone was used to evaluate MVD and no other image tools were used to measure the magnitude of infarct size. Although several studies have shown that IMR is an independent predictor of MVD, radionuclide myocardial perfusion imaging 99mTechnetium Sestamibi single-photon emission tomography and cardiovascular magnetic resonance are still gold standards for measuring myocardial salvage . FurtherIn our study, mechanical strategies were suboptimal in achieving myocardial salvage. Only preloading of third-generation P2Y12 inhibitors was associated with low IMR value which represents a trend of MVD prevention in STEMI patients. Therefore, it is necessary to use third-generation P2Y12 inhibitors according to the current guidelines, and novel procedural techniques should be developed to reduce MVD in patients with STEMI.


Echocardiography represents a first level technique for the evaluation of coronary artery disease (CAD) which supports clinicians in the diagnostic and prognostic workup of these syndromes. However, visual estimation of wall motion abnormalities sometimes fails in detecting less clear or transient myocardial ischemia and in providing accurate differential diagnosis. Speckle tracking echocardiography (STE) is a widely available noninvasive tool that could easily and quickly provide additive information over basic echocardiography, since it is able to identify subtle myocardial damage and to localize ischemic territories in accordance to the coronary lesions, obtaining a clear visualization with a “polar map” useful for differential diagnosis and management. Therefore, it has increasingly been applied in acute and chronic coronary syndromes using rest and stress echocardiography, showing good results in terms of prediction of CAD, clinical outcome, left ventricular remodeling, presence, and quantification of new/residual ischemia. The aim of this review is to illustrate the current available evidence on STE usefulness for the assessment and follow-up of CAD, discussing the main findings on bidimensional and tridimensional strain parameters and their potential application in clinical practice. It is widely known that echocardiography is an essential supporting tool for clinicians in the evaluation of coronary artery disease (CAD). Its application could vary between acute and chronic coronary syndromes (ACS and CCS); however, it has shown not only to aid diagnosis but also to provide useful prognostic information in this clinical setting.The gradual introduction of speckle tracking echocardiography (STE) into clinical practice and its validation for diagnosis and risk stratification in different cardiac disease –4 with aIn fact, speckle tracking analysis is capable to assess typical ischemic subendocardial damage through several parameters: longitudinal strain (LS), which is the most used STE parameter to assess the early affection of subendocardial fibers of all cardiac chambers; bull's eye representation of left ventricular global LS (LVGLS) that provides a regional evaluation of LV injury according to coronary vascularization territories and the specific analysis of endocardial wall deformation properties with the three-layer analysis . These tThe present review is aimed at providing an overview of the different clinical applications of sSTE for the evaluation of CAD, highlighting benefits and challenges of its inclusion in the diagnostic and prognostic workup of ACS and CCS.The latest European Society of Cardiology (ESC) guidelines for the diagnosis and management of non-ST-elevation ACS  : -15.8% to -17.3%] and -19.7% [95% CI: -18.8% and -20.7%]. Moreover, abnormal LVGLS detected moderate-to-severe CAD with a pooled 74.4% sensitivity, 72.1% specificity, 2.9 positive likelihood ratio, and 0.35 negative likelihood ratio. The area under the curve (AUC) and diagnostic odds ratio (OR) were 0.81 and 8.5, respectively  − [end‐systolic strain])/(peak strain or maximum strain change during the cardiac cycle), showing the ratio of the amplitude of PSS to total shortening. The time from aortic valve closure to peak postsystolic strain is used as another parameter .The assessment of PSS is valuable in identifying acute ischemia, because PSS occurs in the myocardium with regional contractile dysfunction . It was Even though the most studied cardiac chamber for the evaluation of CAD is the LV, representing the largest part of myocardium and being responsible of cardiac pump function and output, the other cardiac chambers could be either directly involved in ischemic cardiac damage  in the case of CX lesions and right ventricle (RV) in the case of RCA) or secondarily affected due to postischemic acute or chronic HF .As the application of STE to LA and RV has been increasingly performed for the evaluation of HF, valvular disease, hypertension, etc. –80 showiIn 68 patients with AMI treated with emergent or urgent PCI, peak atrial longitudinal strain (PALS) was lower in patients with a CX culprit lesion than those with culprit lesions in other vessels, whereas the LA volume index did not show any difference. This confirms the importance of LA strain over dimensional measures for the early diagnosis of myocardial damage .r = 0.861; p < 0.001) [In a small study involving patients with stable CAD undergoing ICA, PALS and peak atrial contraction strain (PACS) were significantly reduced in patients with SYNTAX score ≥ 33; notably, these parameters had a close negative correlation with such parameter (< 0.001) . LA stra< 0.001) .Meanwhile, in patients with typical Takotsubo syndrome who underwent transthoracic-Doppler echocardiography during the acute phase and at follow-up (32 ± 18 days later), PALS was transiently impaired at baseline and was associated to in-hospital complications. Moreover, LA strain improved parallel to the dynamic improvement of LV GLS, following the typical feature of a transient myocardial damage of the disease .p = 0.02) [As previously mentioned, RV dysfunction was found by STE in 87 patients with CAD involving RCA, in whom free wall RV LS was an independent predictor of RCA involvement at multivariate analysis  . TherefoMoreover, RV involvement has shown significant prognostic consequences in CAD: patients with acute MI complicated by cardiogenic shock showed a worse prognosis if RV dysfunction by echocardiography was present . Antoni The advances in cardiac imaging and the development of new devices have led to more availability of three-dimensional (3D) echocardiography, which provides further insights on cardiac anatomy and is considered superior to 2D echocardiography for the assessment of cardiac geometry. However, 3D strain value in clinical practice is still debatable, also due to vendor-dependency and the lack of standardization.However, recent studies suggested a potential role of 3D strain for the evaluation of patients with stable and unstable CAD.p = 0.02) and major adverse cardiac events , being superior to bidimensional LVGLS for the prediction of outcome [A recent investigation involving 255 STE-ACS patients undergoing PCI demonstrated that 3D-LVGLS was the strongest predictor of LV reverse remodeling  .Finally, in 130 patients with stable angina pectoris, 3D GLS was correlated with Gensini score, with 88.9% sensitivity and 92.9% specificity being observed for a GLS > −10%; while global area strain (GAS), a new feature of 3D echocardiography which integrates longitudinal and circumferential deformation, had 97.2% sensitivity and 88.1% specificity for a cutoff value > −21% to detect critical CAD (estimated as Gensini score ≥ 20) [Despite these promising results, the diagnostic value of 3D GLS was lower than that of 2D GLS in a recent meta-analysis on the detection of myocardial infarction size ; this suThe major limitation of STE is the lack of defined cutoff values for its confident use in different clinical settings. Furthermore, STE maintains the common limitations of bidimensional echocardiographic measures, such as image quality, operator dependency, and load dependency (lower than LV EF). These limitations could be overcome by the use of 3D echocardiography. However, validated data and standardization among different vendors are necessary to extend its applicability beyond research purposes. Beyond ECG and biomarkers, echocardiography is a milestone for the evaluation of CAD in acute and chronic settings. STE could provide an additive value over visual wall motion assessment both for diagnostic and prognostic assessment, and the inclusion of LVGLS in clinical diagnostic workup of these patients is supported by plenty of evidence and clear advantages overweighing the intrinsic limitations of STE technique . However


Node-positive breast cancer patients often receive chemotherapy and regional nodal irradiation. The cardiotoxic effects of these treatments, however, may offset some of the survival benefit. Cardiac magnetic resonance (CMR) is an emerging modality to assess cardiac injury. This is a pilot trial assessing cardiac damage using CMR in patients who received anthracycline-based chemotherapy and three-dimensional conformal radiotherapy (3DCRT) regional nodal irradiation using heart constraints.Node-positive breast cancer patients (2000–2008) treated with anthracycline-based chemotherapy and 3DCRT regional nodal irradiation  with heart ventricular constraints (V25 < 10%) were invited to participate. Cardiac tissues were contoured and analyzed separately for whole heart (pericardium) and for combined ventricles and left atrium (myocardium). CMR obtained ventricular function/dimensions, late gadolinium enhancement (LGE), global longitudinal strain (GLS), and extracellular volume fraction (ECV) as measures of cardiac injury and/or early fibrosis. CMR parameters were correlated with dose-volume constraints using Spearman correlations.Fifteen left-sided and five right-sided patients underwent CMR. Median diagnosis age was 50 (32–77). No patients had baseline cardiac disease before regional nodal irradiation. Median time after 3DCRT was 8.3 years (5.2–14.4). Median left-sided mean heart dose (MHD) was 4.8 Gy (1.1–11.2) and V25 was 5.7% (0–12%). Median left ventricular ejection fraction (LVEF) was 63%. No abnormal LGE was observed. No correlations were seen between whole heart doses and LVEF, LV mass, GLS, or LV dimensions. Increasing ECV did not correlate with increased heart or ventricular doses. However, correlations between higher LV mass and ventricular mean dose, V10, and V25 were seen.At a median follow-up of 8.3 years, this cohort of node-positive breast cancer patients who received anthracycline-based chemotherapy and regional nodal irradiation had no clinically abnormal CMR findings. However, correlations between ventricular mean dose, V10, and V25 and LV mass were seen. Larger corroborating studies that include advanced techniques for measuring regional heart mechanics are warranted. The use of regional nodal irradiation (RNI) for node positive breast cancer treatment after breast conserving surgery or mastectomy improves local control and survival , 2. HoweMany of the studies demonstrating increased levels of cardiac morbidity and mortality in breast cancer patients receiving radiation include mostly patients treated prior to the mid-1980s , 8, 11. Cardiac magnetic resonance imaging (CMR) is a powerful modality that allows for sensitive evaluation of cancer therapy-induced cardiac changes , 28. WhiThe purpose of this pilot study is to utilize CMR to examine cardiovascular function in women who received both anthracycline-based chemotherapy and RNI using 3DCRT and the use of heart constraints in treatment planning. This study also aims to explore whether CMR-demonstrated changes in perfusion, cardiac function, or cardiac anatomy correlate with the received radiation doses.This Institutional Review Board approved trial (NCT02348684) was conducted by screening a Medical College of Wisconsin database from 2000 to 2008 for lymph node-positive breast cancer patients treated with post-operative 3DCRT RNI with a pre-determined heart constraint . Clinico2 × 300 mm2, matrix of 162 × 192 (in-plane pixel dimensions of 1.56 mm × 1.56 mm), slice thickness = 10 mm, receiver bandwidth (BW) = 1,240 Hz/px, parallel imaging using GRAPPA reconstruction (R = 2), and 25 cardiac phases. Gadolinium contrast agent  was administered at a rate of 0.2 mmol/kg and maximum dose of 20 mmol via peripheral IV. After a 10-min delay, LGE images were obtained for myocardial fibrosis assessment using a T1-weighted, segmented inversion-recovery (IR), fast gradient-echo (GRE) pulse sequence. Imaging parameters were: TR = 750 ms, TE = 1.94 ms, FA = 20°, FOV 340 mm2 × 265 mm2, matrix of 256 × 160, slice thickness = 10 mm, BW = 300 Hz/px, and no acceleration. Coverage of the entire LV was achieved by acquiring 6–8 short-axis (SAX) slices with 10-mm slice spacing, along with long axis images for cross validation. The same heart coverage with identical slice prescriptions were used for both cine and LGE imaging. Qualified cardiac MRI physicians (JR and AW) blinded to the patient identifying information, including dosimetric parameters and side of breast cancer, interpreted the CMR images.CMRs were obtained on a Verio 3T MRI scanner  with patients imaged in the supine position using commercially available RF transmitter/receiver coils. Geometric assessment of the LV was performed without contrast using a steady-state free precession (SSFP) cine sequence. Imaging parameters were: repetition time (TR) = 56.52 ms, echo time (TE) = 1.36 ms, asymmetric echo with factor 0.41, flip angle (FA) = 42°, field of view (FOV) = 252 mmSemi-automated quantification of LV volumes and myocardial mass was performed using CVI42 5.3.0 . Manual identification of the slice range to be segmented and the mitral valve annulus were performed. Optional corrections comprised manual contouring of epicardial or endocardial surfaces to restrict region-growth and adjusting blood sensitivity. LV volumes were quantified as the sum of short axis chamber volumes (2D area × slice thickness) measured during end-diastole  and end-systole . EF was calculated as 100 × (EDV-ESV)/EDV. LV mass was calculated as the product of myocardial volume and specific gravity . Global longitudinal strain (GLS) was calculated from short and long axis SSFP cine sequences utilizing the Tissue Tracking module of CVI42 5.3.0 .P < 0.05 was considered significant.Contrast-enhanced CMR images were analyzed to determine the amount of LGE versus normal LV myocardial volumes. Any hyperenhanced areas of LGE were manually planimetered by visual inspection in each SAX slice, including only regions that were fully enhanced and approximately ≥6 standard deviations (SD) above the mean signal of normal myocardium. Identical slices during cine imaging were compared to identify extent of blood pool and epicardial fat. Global ECV was obtained using the 3-3-5 MOLLI MyoMaps motion-corrected T1 map sequence  pre-contrast and 15 min post-contrast injection, and corrected with hematocrit obtained on the day of the CMR. Statistical analyses were performed using Graphpad Prism Version 7.0  and SAS version 9.3 . Spearman’s correlations were calculated to determine correlation between heart dose and CMR parameters. Wilcoxon’s rank sum tests were used to compare CMR values in left- versus right-sided patients. Fifteen left-sided and five right-sided patients were enrolled in this study after obtaining informed consent, and the patients subsequently underwent CMR. The median age of the patients at diagnosis was 50 years (range 32–77). The median age at CMR was 60 years (range 40–83). The median time after 3DCRT was 8.3 years , the ventricular V10 , and the ventricular V25  has been shown to be an independent risk factor for prediction of cardiovascular events . HoweverA better understanding of the correlation between radiation doses to the heart and subclinical cardiac changes in breast cancer patients in modern series will be helpful to improve the therapeutic ratio of radiation therapy . This piRadiation-induced cardiac events most commonly include pericarditis, myocardial fibrosis/scar, coronary artery disease, and valvular disease , 46. ThePrevious studies have found trastuzumab to be cardiotoxic with 5% prevalence of cardiomyopathy when used as monotherapy and 10–15% prevalence when used with anthracyclines , 61. DesTo date nearly all studies evaluating outcomes by SPECT or other measures of cardiac injury have done so in breast cancer patients who did not have their radiation treatments planned with intent to treat IMC and with a heart constraint in place for dosimetric planning. Over the time period the patients in our study were treated, the heart constraint used for left-sided patients at our institution was ventricular V25 < 10% . This coPerfusion changes have been detected in patients who recently received left-sided radiation therapy by using SPECT imaging, with changes correlating to the radiation treatment fields and with the percent of heart in the radiation fields –69. TherIn this pilot study, we examined women with long-term follow-up after completion of RNI and cardiotoxic chemotherapy using CMR, which can detect functional abnormalities and provide excellent spatial resolution. Taken together, our CMR data suggests that in this cohort there is no significant cardiac injury from receiving both RNI and cardiotoxic chemotherapy, despite relatively high mean heart doses received by a significant proportion of left-sided patients. It is important to note that patients included in this trial had no clinical evidence of cardiac disease at the time of treatment or prior to their study participation. Prior studies have demonstrated that cardiac events are more frequent after radiation in patients with baseline heart disease, thus these results are likely not applicable to this group .In this study, positive correlations were found between ventricular dose volume parameters and LVMI. However, there was no evidence of increased ECV with increasing heart or ventricular radiation doses. It may be that even more refined regional cardiac analysis is necessary to study radiation-induced cardiac changes, as correlations may not be as evident when whole heart or ventricular doses are compared to global heart function. Indeed, the use of standardized cardiac heart substructure contours may allow more refined analysis of risk of cardiac disease based upon dose localization within the heart . For futStrengths of this study include the long median follow-up in patients who received anthracyclines and regional nodal irradiation, as well as receipt of radiation treatment using 3DCRT which allowed determination of cardiac and ventricular doses. However, this pilot study is limited by the small cohort of patients, as well as the lack of details regarding exercise capacity, detailed clinical symptoms, or cardiac biomarkers, although hypothesis-generating findings are seen with respect to ventricular radiation doses and LVMI. The CMR values were largely within normal limits despite a median MHD of >4 Gy for breast cancer patients enrolled in this study. This finding may reflect that in this population of patients without clinical cardiac disease there is a higher threshold for cardiac injury. Alternatively, this finding could mean that radiation therapy planned with cardiac constraints successfully limited partial heart injury, unlike prior studies evaluating cardiac injury from radiation delivered without constraints. It could also be that differences were present, but they were masked by the inherent uncertainties of in the estimation methods used. There is also the possibility of bias, as these 20 women self-selected from a cohort of women invited by letter to return for cardiac MRI. In addition, significant differences could have been present, but were masked by the inherent uncertainties in the estimation methods to obtain CMR values. For future studies, additional more sensitive analyses using CMR with multiple geometric views, regional strain analysis, and feature tracking may improve sensitivity to detect subclinical radiation changes. In addition, baseline CMR data was not available for this cohort of patients. However, the correlations seen between ventricular dose volume parameters and LVMI values are hypothesis-generating. Larger corroborating studies are warranted to further examine the utility of CMR in detection of therapy-induced heart disease in node positive breast cancer patients who receive both cardiotoxic chemotherapy and radiation.All datasets generated for this study are included in the article/The studies involving human participants were reviewed and approved by Medical College of Wisconsin Institutional Review Board. The patients/participants provided their written informed consent to participate in this study.JW, JAB, JR, and CB contributed to the conception and design of the study. CB, PP, JB, AW, AC, and JR collected the data. JR, CB, M-JZ, and DE performed statistical analyses. JR, AW, JLS, AC, and E-SHI interpreted the data. AMS and CB wrote initial drafts of the manuscript. JAB, JW, JFW, and LP wrote and edited sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.JAB has received a travel grant from Ion Beam Applications. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Electrocardiography is the first‐choice technique for detecting left ventricular hypertrophy in patients with arterial hypertension. It is necessary to know the probable outcome for every patient during the treatment, with the aim of improving cardiovascular event prevention.Certain electrocardiographic criteria for left ventricular hypertrophy may predict outcomes of patients with left ventricular hypertrophy during a 15‐year follow‐up.2). Electrocardiographic left ventricular hypertrophy was determined by means of Gubner‐Ungerleider voltage, Lewis voltage, voltage of R wave in aVL lead, Lyon‐Sokolow voltage, Cornell voltage and Cornell product, voltage RV6 and RV5 ratio, Romhilt‐Estes score, Framingham criterion and Perugia criterion.Fifteen‐year prospective study of 83 consecutive patients  with echocardiographic left ventricular hypertrophy (left ventricular mass index 170.3 ± 31.6 g/mP < 0.05), Lewis voltage , Cornell voltage , and Cornell product  were more frequent in a group of patients with composite events. Odd ratio for Cornell product was 4.819 (95% CI 1.486‐15.627).One or more composite events were registered in 32 (38.5%) patients during 15‐year follow‐up. Positive Lyon‐Sokolow score (17.6% vs. 47.3%; Patients with echocardiographic left ventricular hypertrophy who had positive Lewis voltage, Lyon‐Sokolow voltage, Cornell voltage, and Cornell product showed worse 15‐year outcome. The strongest predictor of cardiovascular events was positive result of Cornell product. Electrocardiography (ECG) is the first‐choice technique for detecting left ventricular hypertrophy (LVH) in patients with hypertension due to its wide‐scale availability, low cost, repeatability, and established value prognostic.The aim of the paper is to investigate clinical and prognostic significance of electrocardiographic criteria of hypertensive left ventricular hypertrophy during 15‐year follow‐up period.22.1This study represented an extension of our previously published study which had analyzed the above stated criteria during 5‐year follow‐up period.The diagnosis of hypertension, target values of systolic and diastolic blood pressure, pharmacological therapy, exclusion criteria, and verification of adverse events were the same as in our previously published study.2.26 and RV5 ratio (positive >1), Romhilt‐Estes score, Framingham criterion, and Perugia criterion . Additionally, Gubner‐Ungerleider voltage as RD1 + SD3 ≥ 2.5 mV, and Lewis voltage as (RD1 + SD3) — (SD1+ RD3) ≥ 1.7 mV were used for confirming LVH. Positive Lyon‐Sokolow voltage was defined as SV1 + RV5 or V6 ≥ 3.5 mV, or in accordance with European Society of Cardiology Guidelines Committee as ≥3.8 mV.3 + RaVL > 2.0 for women and >2.8 for men. Positive Cornell product was defined as SV3 + RaVL × QRS duration ≥244 mV × ms. Left ventricular strain was defined as ST‐segment depression ≥0.1 mV plus T‐wave asymmetric inversion in V2 to V6 and in peripheral leads . Framingham criterion was positive if left ventricular (LV) strain plus ≥1 voltage criterion . Perugia criterion was positive if SV3 + RaVL >2.4 mV (men), >2.0 mV (women), and/or LV strain, and/or Romhilt‐Estes score ≥5. Positive Romhilt‐Estes score was defined as ≥5 points and calculated from six ECG features with a specific value of points for each feature: R or S wave in any limb lead ≥2.0 mV or S wave in V1 or V2 ≥ 3.0 mV or R wave in V5 or V6 ≥ 3.0 mV (three points); P‐terminal force defined as terminal negativity of P wave in V1 ≥ 0.10 mV in depth and ≥0.04 ms in duration (three points); LV strain defined as ST segment and T wave in opposite direction to QRS in V5 or V6, without digitalis (three points); left axis deviation defined as QRS axis less than or equal to −30° (two points); QRS duration ≥0.09 ms (one point); and intrinsicoid deflection in V5 or V6 ≥ 0.05 ms (one point).LVH was determined by means of Gubner‐Ungerleider voltage, Levis voltage, voltage of R wave in aVL lead (positive >1.1 mV), Lyon‐Sokolow voltage, Cornell voltage and Cornell product, voltage RV2.32 for women and ≥134 g/m2 for men.Detection of echocardiographic left ventricular hypertrophy was done by means Acuson Sequoia C250 with 3.5 MHz, using M‐mode technique.2.4The first test for detecting coronary artery disease implied treadmill Bruce protocol. Ergometric testing was performed every second year or at more frequent intervals, if necessary . If the test data were not sufficient, stress echocardiography was carried out. Patients with positive exercise test (ST depression of ≥1 mm) were subjected to coronary angiography. More details about exercise testing protocol could be seen in our previously published study.2.5In addition to continuous blood pressure monitoring in medical office, each patient was subjected to 24‐hour ambulatory blood pressure monitoring .2.6χ2 tests. Multiple regression analysis and the odds ratio were calculated for all electrocardiographic criteria of left ventricular hypertrophy in terms of presence of cardiovascular events. Receiver operating characteristic curve analysis was performed.Statistical analysis was performed by means of SPSS software . Average values and SDs were calculated. Percentages were used for descriptive variables. Differences between groups were tested by ANOVA and 3Statistically, both groups, that is, group with adverse events and group without adverse events, had the same basic characteristics and received the same therapy at the end of the study Table .Parameters obtained by 24‐hour ambulatory blood pressure monitoring and the ones obtained by echocardiography were shown in Table Both groups had similar functional capacity during exercise testing measured by METs ‐ metabolic equivalents (without adverse events 6.9 ± 2.5 METs vs. with adverse events 6.3 ± 2.2 METs) and by double product (155.1 ± 51.5 vs. 145.7 ± 63.2). Moreover, there was no difference in terms of other parameters obtained by cardiac stress test. The total of 32 (38.5%) patients had eccentric LVH, 31 (37.4%) patients had concentric LVH, and 20 (24.1%) patients had disproportionate septal LVH.P < 0.05). Positive Cornell product for LVH was statistically significant for patients with cardiovascular events (P < 0.01). Multiple regression stepwise analyses highlighted Cornell product  as compared to other criteria of hypertrophy, after adjustments in terms of gender, age, body mass index (BMI), and LVMI .Positive Lyon‐Sokolow score, Lewis voltage and Cornell voltage Table  were mor4The prevalence of arterial hypertension in Serbia is 42.7%.4. The criteria provide an improved sensitivity for the ECG diagnosis of LVH compared to existing criteria.The incidence of left ventricular hypertrophy may vary and mostly depends on diagnostic method. The standard ECG is reliable for diagnosing LV hypertrophy, regardless of the presence of atrial fibrillation or sinus rhythm at the time of ECG recording.Additionally, prognostic significance of LVH may vary. Leigh et al.Nowadays, numerous experts attempt to redefine the existing LVH criteria by using magnetic resonance as gold standard. Rodrigues et al.After completing ergometric test, coronary heart disease was excluded from this study. Patients included in the study showed no difference in stress level or double product. The authors of numerous studies showed that low achieved heart rate, exercise capacity and Duke Treadmill score were dominant predictors of worst prognosis.P < 0.0001) and 2.83  when SV1 + RV5 was classified into two groups at threshold values of 35 and 40 mm, respectively. In terms of analyzing Lyon‐Sokolow voltage, odds ratio in this study was 3.630  for composite cardiovascular events. Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study proved that the reduction of electrocardiogram hypertension resulted in the reduction of cardiovascular risk, regardless of the changes in blood pressure.Even though there were no differences between the tested groups in terms of basic features, medical treatment, blood pressure level, echocardiography, and ergometric parameters, the study showed difference in distribution of electrocardiographic markers of left ventricular hypertrophy. Having in mind the sensitivity of specific criteria and small number of cardiovascular events, which was a limitation of this study, not all known criteria of electrocardiographic left ventricular hypertrophy could undergo a valid statistical analysis. The study of Estes et al.5Positive Lewis voltage, Lyon‐Sokolow voltage, Cornell voltage and Cornell product showed worse 15‐year outcome in patients with hypertensive heart. The strongest predictor of cardiovascular events was positive result of Cornell product.The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non‐financial interest, such as personal or professional relationships, affiliations, knowledge or beliefs in the subject matter or materials discussed in this manuscript.


Catheter ablation of ventricular tachycardia (VT) has emerged as a superior alternative to antiarrhythmic drug therapy in patients with ischemic cardiomyopathy, with the vast majority of ischemic VT being ablation from the endocardial surface of the left ventricle (LV). While rare, the possibility of ischemic right ventricular (RV) VT should also be entertained, especially in patients with previous myocardial infarction and in those individuals in whom LV endocardial ablation fails to abolish VT. Further, success rates remain disappointing in some of these cases, often owing to difficulties in mapping the tachycardia due to hemodynamic instability during VT. We report a case of hemodynamically unstable ischemic VT successfully ablated from the endocardial surface of the LV and RV using a substrate mapping approach in a patient with a large inferior myocardial infarction, involving RV infarction. We report a case of scar-related VT successfully ablated from the endocardial surface of the inferobasal RV and LV in a patient with ICM.Radiofrequency (RF) catheter ablation has been shown to be effective in patients with recurrent ventricular tachycardia (VT) and has been indicated as superior to escalating antiarrhythmic drug (AAD) therapy in patients with ischemic cardiomyopathy (ICM).A 58-year-old male with a past history of ICM and LV systolic dysfunction (LV ejection fraction of 30%) was referred to our electrophysiology laboratory for RF catheter ablation of VT. He had a previously placed, primary-prevention dual-chamber implantable cardioverter-defibrillator (ICD) and a recent history of multiple appropriate shocks for VT that had been recurrent despite escalating doses of amiodarone to 400 mg daily and metoprolol succinate to 150 mg daily, along with the addition of mexiletine 150 mg three times daily. Stress myocardial perfusion imaging demonstrated scarring in the inferior, inferolateral, and apical LV walls but did not reveal evidence of reversible ischemia. Data from transthoracic echocardiography (TTE) were concordant, showing akinesis and aneurysmal deformity of the inferior and inferolateral LV myocardium. The RV was poorly visualized on TTE, though on intracardiac echocardiography (ICE), the inferior and inferobasal RV were hypokinetic, with a thin, hyperechoic appearance of the myocardium.®; Stereotaxis, Inc., St. Louis, MO, USA).After verbal and written informed consent were obtained, the patient was brought to the electrophysiology laboratory for the procedure and placed under general anesthesia. Venous access was obtained and diagnostic catheters were placed in the RA appendage, His position, and RV. An ICE catheter was used to guide transseptal catheterization and for image integration using the CartoSOUND™ enhanced mapping software . Three-dimensional electroanatomic mapping of the LV and RV was performed using the CARTO™ 3 RMT mapping system  and a magnetic catheter maneuvering system (Epoch. VT-1 and VT-2 both had left bundle branch block (LBBB) morphology with a superior axis. VT-3 and VT-4 had a right bundle branch block morphology, again with superior axis. All four VTs were hemodynamically unstable and required direct-current cardioversion. Because of this, we opted to perform substrate mapping during RA appendage pacing (pacing cycle length: 800 ms) to identify isolated late ventricular potentials (ILPs), as previously described.5 We first performed mapping of the LV, identifying late fractionated ILPs in the inferobasal, inferolateral, and apical walls . A total of 42 RF applications (RF power: 30–50 watts) were delivered in the inferior RV endocardium, targeting ILPs. However, after LV endocardial ablation was complete, VT-2 (LBBB and superior axis morphology) was still easily inducible. We therefore decided to map the RV, again targeting ILPs. A large area of low bipolar voltage (< 0.5 mV) was identified in the inferobasal RV wall with associated ILPs . Pacemapping from this area showed a similar morphology to those of VT-1 and VT-2. A total of 38 RF applications were delivered in the inferior RV endocardium, targeting ILPs within the low voltage area. Following ablation of ILPs in the RV, VT was no longer inducible and the study was completed.At the beginning of the study, four VT morphologies were easily inducible using burst pacing from the RV The patient remained free of ICD discharges during hospitalization and was continued on AAD therapy with amiodarone, mexiletine, and metoprolol succinate on discharge. The patient is still alive and has not received any shocks four months after ablation.8 We report a case of successful RF catheter ablation of VT originating from an inferobasal RV scar in a patient with ICM. While rare in isolation, RV myocardial infarction (MI) complicates 25% to 50% of inferior MIs10 and is therefore capable of producing the substrate for reentrant VT. However, the occurrence of ischemic RV VT is confined to case reports12 and optimal mapping and ablation techniques have not been described. Of note, the clinical presentations reported in cases of ischemic RV VT vary significantly. Menz et al. describe two patients who underwent successful VT ablation from the RV septum after failed ablation in the LV septum, though one presented with a prior inferior infarct and the other presented with a prior anterior infarct.12 A third case described by Shimizu et al. involved successful VT ablation from the RV free wall of a patient with a prior RV infarct.11 All VT in these cases had LBBB morphology.This case highlights the potential importance of RV VT in patients with ischemic cardiomyopathy and shows that a substrate-mapping approach can successfully guide ablation in these cases. Catheter ablation of RV VT is typically discussed in the setting of RV outflow tract VT; RV scarring related to surgery for congenital heart disease (CHD); infiltrative cardiomyopathies; scarring in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC); or, rarely, in patients with Brugada syndrome.10 which might suggest an RV origin and thus cause confusion regarding VT localization. Several factors limit the usefulness of the surface ECG in this regard, including the presence and degree of prior myocardial scar, a lack of concordance between the scar and exit site locations, heart morphology and variations in chest wall anatomy, the effects of concomitant medical therapy, and the integrity of the His-Purkinje system.13 Nonetheless, the surface ECG can provide the electrophysiologist with clues regarding the “regionalization” of the VT, as a first step towards successful mapping and ablation. As alluded to, a QS pattern in lead V1  is suggestive of an RV VT origin because the LV is activated late via slow myocardial conduction, similar to in the case of true LBBB. While VT originating in the LV septum can have a similar appearance, septal VT tends to have a narrower QRS as compared with VT originating in the free wall, though anisotropic myocardial conduction (as may present in patients with other areas of scar of infiltrative disease) may invalidate this assumption.13 In this case, the VT-2 morphology, which predominated after LV substrate modification, was very wide and would be less likely to be present originating from the LV septum as based on the surface ECG. However, other generalizations regarding VT origin based on surface ECG morphology may not hold true. For example, it has been reported that negative precordial concordance is suggestive of an apical sepal origin,13 yet, in this case, VT-2 showed negative concordance and was successfully ablated from the inferobasal RV. These contradictions may be related to different exit sites from the scar into the myocardium, presence of other abnormal areas of myocardium, or incorrect assumptions regarding the position of the heart in the chest, as previously mentioned. Because of these issues, the possibility of an RV origin of the VT should be thoroughly examined irrespective of QRS morphology on the surface ECG, whenever ablation in the LV fails to eliminate the VT.Despite the rarity of ischemic RV VT, approximately one-third of ischemic VT originating from the LV demonstrated a LBBB morphology on the electrocardiogram (ECG),12 In a case series of 18 patients who presented for VT ablation with evidence of prior septal infarction, 11 (61%) had evidence of RV scarring as assessed by bipolar voltage mapping, 73% of whom were confined to the RV septum. Additionally, 10% of the inducible VTs had a critical isthmus in the RV septum and 82% of these could only be successfully ablated from the RV. All of the RV VTs in this series had LBBB morphology.14 Our case demonstrates that, in addition to the interventricular septum, the inferobasal RV may also be a site of origin for ischemic VT, especially in patients with prior inferior MI.In our case, extensive LV endocardial ablation of ILPs within the areas of low bipolar voltage (< 0.5 mV) failed to abolish VTs with LBBB morphologies, which prompted a search for an alternative endocardial origin of the arrhythmia. While most VT in patients with ICM is felt to originate from the LV subendocardium, the importance of alternative sites in patients with ischemic heart disease  should not be overlooked, especially in cases in which VT remains inducible following extensive LV ablation, or when sites of earliest activation are found in the LV septum.15 Recent data suggest that VT induction and mapping before ablation prolongs procedure times, increases radiation exposure, and increases the need for electrical cardioversion without improving ablation efficacy,5 thus potentially favoring a substrate mapping approach in some patients with scar-related VT. The approach involves identifying areas of low voltage and corresponding ILPs that represent surviving myocardial bundles within the infarcted scar. In general, normal tissue voltage is defined as > 1.5 mV, where areas of myocardium with < 0.5 mV are felt to represent scar, though these definitions vary based on endocardial, mid-wall, and epicardial location of scar as well as the underlying disease process.5 Studies comparing VT ablation using induction and activation mapping versus substrate mapping have yielded conflicting results, though these studies vary with their respect to timing of late potentials, scar voltage, degree of fractionation, and etiology of VT.15 In this case, we were able to identify ILPs in the inferobasal RV that corresponded to an area of low bipolar voltage (< 0.5 mV). Ablation in this area rendered the patient’s VT noninducible, despite being unable to identify sites of early activation during VT.While mapping during VT is ideal in order to fully define the reentrant circuit and identify earliest activation, this is often not possible due to hemodynamic instability, as occurred in this case. Substrate mapping has emerged as an alternative to activation mapping in patients with hemodynamically unstable or otherwise unmappable VT.This case demonstrates the potential importance of RV endocardial sites of VT origin in patients with ICM, especially those with previous inferior MI involving RV infarction. Mapping in these areas should be considered in patients whose VT remains inducible despite ablation in the LV endocardium, or in patients in whom earliest activation during VT is recorded from sites in the LV septum. Further, this case demonstrates the feasibility of substrate mapping to guide ablation in the RV in patients with ischemic RV scarring. Finally, ECG criteria for differentiating the RV from the LV for origin of VT are imperfect, and it is important to recognize the possibility of an RV origin, irrespective of QRS morphology, on the surface ECG in patients with ICM.