Bakgrund Hjärtinfarkt är en vanligt förekommande sjukdom där livsstil påverkar risken att drabbas. Med livsstilsförändring inom områdena tobaksbruk, kostvanor, motion och alkoholkonsumtion kan en stor del av insjuknande i hjärtinfarkt förebyggas. Patientens attityd kan vara avgörande i arbetet med livsstilsförändringen. Syfte Syftet med litteraturstudien var att beskriva vilka faktorer som påverkar patienters attityder till eventuell livsstilsförändring efter hjärtinfarkt. Metod Studien är gjord som en litteraturöversikt baserad på 14 vetenskapliga artiklar med kvalitativ, kvantitativ och blandad ansats. Resultat Det framkom tio kategorier som enskilt eller tillsammans påverkade patientens attityd till livsstilsförändring. Faktorerna var rädsla, medvetenhet, stöd, självdisciplin, egna prioriteringar, fysiska hinder, tidsperspektiv, erfarenheter hämtade från omgivningen, vilja att återgå till tidigare fysisk kapacitet och livsåskådning. Slutsats Deltagarnas attityder påverkades tydligt av de framkomna faktorerna. En deltagare som fick stöd, hade medvetenhet om sitt tillstånd, viljan att återgå till tidigare fysisk kapacitet och hade god självdisciplin hade ökad motivation till att genomföra en livsstilsförändring efter hjärtinfarkten. I motsats till detta fanns fysiska hinder och tidsperspektiv som påverkade attityden negativt till att genomföra livsstilsförändring. Rädsla, egna prioriteringar och livsåskådning kunde påverka attityden till livsstilsförändring i både positiv och negativ riktning. / Background Myocardial infarction is a common disorder in which lifestyle affects risk. With lifestyle changes within physical activity, diets, tobacco use and alcohol consumption a great amount of myocardial infarction can be prevented. Patients´ attitudes can be crucial in the process of lifestyle change. Aim The aim of the study was to describe the factors that influence patients´ attitudes to potential lifestyle change after myocardial infarction. Method The study is designed as a literature review based on 14 scientific articles with qualitative, quantitative and mixed methods. Results Ten factors emerged that separately or together affected patients´ attitudes to lifestyle change. The factors were fear, awareness, support, self-discipline, own priorities, physical obstacles, perspective of time, experience collected from the entourage, desire to return to past physical capacity and conception of life. Conclusion The participants’ attitudes were clearly affected by the emerged factors. A participant who had support, awareness, desire to return to past physical capacity and had self-discipline had increased motivation to implement lifestyle change after myocardial infarction. In contrast physical obstacles and perspective of time affected the attitude negatively to implement lifestyle change. Fear, own priorities and conception of life could affect attitudes to lifestyle change in both positive and negative direction.

This report examines differences in risk of myocardial infarction and stroke (cardiovascular events) between the cyclooxygenase-2 (COX-2) inhibitors Rofecoxib, Celecoxib, and Valdecoxib, and the traditional nonsteroidal anti-inflammatory agents (NSAIDs) Naproxen and Ibuprofen, as well as Meloxicam, a preferential COX-2 inhibitor. The population studied was the DoD TRICARE beneficiary population greater than age 40 during the study period. In September of 2004, Rofecoxib was removed from the market due to an increased risk of cardiovascular events. In February of 2005, the Food and Drug Administration (FDA) examined the entire class of COX-2 inhibitors and recommended that Valdecoxib also be withdrawn from the market. According to Department of Defense TRICARE prescription records, COX-2 inhibitor prescription numbers were increasing rapidly and more than $7 million was spent on these agents alone in July of 2004. Logistic regression was used to analyze TRICARE prescription and diagnosis data from calendar years 2002, 2003, and 2004 for cardiovascular event risk comparisons among various NSAIDs. Rofecoxib was found to have a significantly increased risk of cardiovascular events when compared with all other medications in the study, including Valdecoxib. Odds ratios for comparison with Valdecoxib, Celecoxib, Meloxicam, Ibuprofen, and Naproxen were 1.09, 1.14, 1.15, 1.28, and 1.23. Valdecoxib showed a significant increase compared to Ibuprofen, Naproxen, and Celecoxib (odds ratios 1.21, 1.16, and 1.06). Ibuprofen showed a significantly decreased risk relative to all medications except Naproxen. When considering only cardiovascular risk, this study suggests prescribers should consider Ibuprofen or Naproxen as the primary agent of choice, with Meloxicam, and Celecoxib as reasonable second choices. Ultimately, the decision must also weigh the patient's risk of gastrointestinal side effects and cost of therapy.

Bakgrund : Vid hjärt- och kärlsjukdomar är kvinnor degraderade, de får sämre behandling jämfört med män, mindre forskning sker på kvinnor och de får oftare fel eller ingen diagnos. I och med att mannen varit normen och referensramen, behandlas även kvinnor efter samma kriterier. Kvinnors symtom på hjärtinfarkt skiljer sig från mannens. Syftet : Syftet med litteraturöversikten var att belysa kvinnors upplevelse av att drabbas av hjärtinfarkt. Metod : Studien genomfördes som en litteraturöversikt. Artiklarna söktes i databaserna Cinahl och PubMed vilket resulterade i elva kvalitativa artiklar. Resultat : Kvinnor upplevde fysiska symtom från olika delar av kroppen, det kan vara från mag-tarmkanalen, extremiteter och bröstregionen. De förnekar symtomen och försöker komma på orsaker till varför de uppstår. Vården ger bristfällig information och tar dem inte på allvar vilket leder till osäkerhet. Kvinnor mår fortfarande dåligt flera månader efter infarkten och har svårt att klara vardagen. De behöver stöd från familjen som kan stötta och finnas till, även om de inte alltid berättar hur de mår. Slutsats : Kvinnor upplever en rad olika symtom när de drabbas av hjärtinfarkt och symtom kan uppstå från olika delar på kroppen, inte bara i bröstregionen. De upplever också att vårdpersonalen ger bristfällig information och inte tar dem på allvar när de söker för sina symtom. Många kvinnor har kvarvarande symtom flera månader efter infarkten. / Background : When it comes to heart disease, women are degraded. Women get worse treatment, more often wrong or no diagnosis and research is less in women. As the man is the norm and reference the women also get treated after the same criteria. Women’s symptoms are different compered to men. Aim : The aim of this study was to explore women’s experiences of suffering from a myocardial infarction. Methods : The design is a literature review. Data collection occurred in the databases Cinahl and PubMed which resulted in eleven qualitative articles. Result s: Women experienced symptoms from different parts of the body, which may be from the gastrointestinal area, extremities and breast region. They deny the symptoms and try to find reasons why they occur. Care provides give lack of information and does not take them seriously, which causes women to feel insecure. Women still feel bad several months after the infarction and have difficulty coping with everyday life. They need support from the family that can give them support and help, although they do not always tell family how they feel. Conclusion : Women experience a variety of symptoms when they suffer from myocardial infarction, and symptoms may start from different parts of the body, not just in the breast region. They also experience that the caregiver provides inadequate information and do not take them seriously when they seek medical care. Many women have remaining symptoms several months after the infarction.

OBJECTIVES The aim of this study was to test the hypothesis that hypothermia and early reperfusion are synergistic for limiting infarct size when an acutely occluded coronary is associated with cardiac arrest. BACKGROUND Cohort studies have shown that 1 in 4 post-cardiac arrest patients without ST-segment elevation has an acutely occluded coronary artery. However, many interventional cardiologists remain unconvinced that immediate coronary angiography is needed in these patients. METHODS Thirty-two swine (mean weight 35 +/- 5 kg) were randomly assigned to 1 of the following 4 treatment groups: group A, hypothermia and reperfusion; group B, hypothermia and no reperfusion; group C, no hypothermia and reperfusion; and group D, no hypothermia and no reperfusion. The left anterior descending coronary artery was occluded with an intracoronary balloon, and ventricular fibrillation was electrically induced. Cardiopulmonary resuscitation was begun after 4 min of cardiac arrest. Defibrillation was attempted after 2 min of cardiopulmonary resuscitation. Resuscitated animals randomized to hypothermia were rapidly cooled to 34 degrees C, whereas those randomized to reperfusion had such after 45 min of left anterior descending coronary artery occlusion. RESULTS At 4 h, myocardial infarct size was calculated. Group A had the smallest infarct size at 16.1 +/- 19.6% (p < 0.05). Group C had an intermediate infarct size at 29.5 +/- 20.2%, whereas groups B and D had the largest infarct sizes at 41.5 +/- 15.5% and 41.1 +/- 15.0%, respectively. CONCLUSIONS Acute coronary occlusion is often associated with cardiac arrest, so treatment of resuscitated patients should include early coronary angiography for potential emergent reperfusion, while providing hypothermia for both brain and myocardial protection. Providing only early hypothermia, while delaying coronary angiography, is not optimal. (J Am Coll Cardiol Intv 2016; 9: 2403-12)

The myocardium is known to release CPK, LDH1 , and GOT in response to ischemia as a result of myocardial infarction. This study was designed to induce the release of cardiac enzymes without adversely effecting the myocardium by perfusion hypothermia, thereby suggesting that these enzymes are not as specific in the diagnosis of myocardial infarction as once thought. Hypothermia was by in vivo perfusion of the left anterior descending coronary artery. Enzyme activity was measured from sera samples spectrophotometrically and electrophoretically. Significant CPK and LDH1 increases were observed in animals perfused between 25 and 19 C. These results indicate that, while heart function remained unchanged, an alteration occurred in the membrane integrity of the myocardial cells.

Title: Analysis of pharmacotherapy and drug related problems in patients with arterial hypertension in Greece Student: Zisis Papadopoulos Tutor: Jiri Vlcek Department of Social and Clinical Pharmacy, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Background: Arterial hypertension or high blood pressure is a chronic medical condition which is characterized by elevated blood pressure in the arteries and is an important risk factor for future development of cardiovascular disease. Also belongs to asymptomatic diseases because it usually does not cause symptoms for years until a vital organ is damaged. Moreover is a major cause of morbidity and mortality, due to its association with some other serious diseases like coronary heart disease, cerebrovascular disease, atherosclerosis, renal disease, dyslipidemia, diabetes, obesity and metabolic syndrome. Arterial hypertension for adults, who don't suffer from any other kind of diseases, is defined by an elevation of blood pressure to 140 / 90 mm Hg or to higher values. Aim: In the theoretical part the main aim is to analyze information regarding etiopathogenesis, diagnostic methods and treatment strategies of arterial hypertension, as well as classification and causes of drug-related-problems to antihypertensive agents. In the...

L'infarctus du myocarde (IDM) est l'une des principales causes de morbi-mortalité dans les pays développés et ce malgré l'amélioration enregistrée ces dernières années dans sa prise en charge thérapeutique. L'obésité est classée comme étant un facteur de risque majeur pour les maladies coronaires par l'American Heart Association, et concerne 14,5 % de la population française (enquête ObEpi-Roche/INSERM, 2009). En utilisant un modèle expérimental d'obésité, la souris ob/ob génétiquement dépourvue en leptine, l'objectif du présent travail de thèse a été d'étudier l'efficacité de stratégies cardioprotectrices comme le postconditionnement (PCD) ischémique ou l'exercice physique chronique contre l'IDM. La première partie de ce travail de thèse a mis en évidence une perte de la cardioprotection par PCD ischémique au cours de l'obésité. L'étude des voies de signalisation aura permis de mettre en évidence l'implication des protéines phosphatases PTEN, MKP3 et PP2C dans l'inefficacité du PCD. La seconde partie de ce travail de thèse a montré un effet cardioprotecteur de l'exercice physique chronique contre l'IDM dans un contexte expérimental d'obésité. Cet effet est associé à une augmentation des défenses enzymatiques antioxydantes, à une amélioration des fonctions mitochondriales, à une activation des voies de signalisation cardioprotectrices RISK et SAFE et enfin à une diminution des protéines phosphatases impliquées dans la régulation négative des acteurs des voies de signalisation cardioprotectrices. La preuve scientifique des bienfaits de l'exercice est aujourd'hui un argument de poids pour poursuivre les efforts entrepris par les pouvoirs publics ces dernières années à travers le Programme National Nutrition Santé pour favoriser la pratique d'une activité physique et sportive et en particulier chez les obèses. / Myocardial infarction (MI) remains the leading cause of morbidity and mortality in the developing countries despite significant therapeutic advances over these last years. Obesity is a major risk factor for coronary heart disease according to the American Heart Association and concern 14.5% of the French population (ObEpi-Roche/INSERM survey, 2009). Using the leptin-deficient ob/ob mice, an animal model of obesity, the aim of the present thesis was to investigate the efficacy of cardioprotective strategies such as ischemic postconditioning (PCD) or chronic physical exercise against MI. In the first part of this thesis, we have found that the cardioprotective effects of PCD vanish with obesity. The investigation of the cardioprotective pathways has revealed that protein phosphatases such as PTEN, MKP3 and PP2C are involved in the inability of PCD to protect the heart. The second part of this thesis has demonstrated for the first time a cardioprotective effect of chronic physical exercise against MI in an experimental model of obesity. This effect was associated with increased antioxidant enzymes, improved mitochondrial function, activation of the cardioprotective RISK and SAFE pathways and finally a decrease in the related protein phosphatases levels. The scientific proofs given by this work underlines the “Programme National Nutrition Santé” developed by the French government to encourage all people and especially obese people to observe physical and sport activities.

Orientador: Marcos Ferreira Minicucci / Resumo: Introdução: As doenças cardiovasculares são as principais causas de mortalidade em todo o mundo. O infarto agudo do miocárdio com supradesnivelamento de segmento ST (IAMCSST) vem apresentando redução da mortalidade após a introdução das terapias de reperfusão. Diversos fatores estão associados a pior prognóstico e foi evidenciado que massa e função muscular podem estar associadas a comorbidades como hipertensão arterial sistêmica, síndrome metabólica, diabetes mellitus, obesidade e morte precoce. A força e massa muscular são regulados por diversos fatores entre os quais podemos destacar a miostatina. A miostatina, conhecida classicamente como regulador negativo da musculatura tem apresentado papel controverso na literatura, sendo por vezes relacionada a perda de massa muscular. Até o presente momento não há estudos investigando o papel da miostatina nas síndromes coronarianas agudas. Objetivo: O objetivo do presente estudo é avaliar a associação dos valores séricos de miostatina, com a massa e função muscular, tempo de internação e mortalidade hospitalar de pacientes com IAMCSST admitidos no Hospital das Clínicas da Faculdade de Medicina de Botucatu. Materiais e métodos: Trata-se de um estudo prospectivo observacional com pacientes admitidos com diagnóstico de IAMCSST no Hospital das Clínicas da Faculdade de Medicina de Botucatu, no período de maio de 2018 a fevereiro de 2019. Foram incluídos pacientes com IAMCSST, que aceitaram participar e foram recrutados nas primeiras 48 ... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

No Brasil, as doenças cardiovasculares constituem-se nas principais causas de mortalidade, sendo o infarto agudo do miocárdio a entidade nosológica mais freqüente dentre as doenças isquêmicas do coração. Os fatores de risco que predispõem as pessoas a essa doença estão relacionados a hábitos do estilo de vida e história familiar. Assim, esta investigação, de natureza descritiva, pretende identificar os fatores de risco relacionados ao meio ambiente, à biologia humana, estilo de vida, e sistema de saúde de pacientes internados em um hospital privado, até 48 horas após a ocorrência de infarto agudo do miocárdio, identificar o conhecimento quanto aos fatores de risco para o desenvolvimento de novos problemas de saúde e verificar se algumas variáveis, relacionadas aos fatores de risco de pacientes infartados em hospital público e privado, são semelhantes. O referencial teórico foi o Modelo de Campo de Saúde que compõe elementos relacionados ao meio ambiente, biologia humana, estilo de vida e sistema de saúde. Foram entrevistados 31 pacientes internados, em um hospital privado de uma cidade do interior do Estado de São Paulo, no período de janeiro a julho de 2003, após assinatura do termo de consentimento informado. Os resultados revelam que, quanto ao meio ambiente, a maioria dos pacientes era alfabetizada, 11 (35,5%) tinha o primeiro grau completo, 10 (32,2%) eram aposentados e donas-de-casa, 24 (77,4%) trabalhavam em torno de 8 a 10 horas por dia e tinham somente um emprego, e a renda familiar mensal, para 19 (61,3%), encontrava-se na faixa de 5 a 15 ou mais salários-mínimos, 22 (70,9%) eram casados e 15 (48,3%) tinham três ou mais filhos, 21 (67,7%) eram procedentes de Ribeirão Preto e região e todos residiam em zona urbana. Em relação à biologia humana, 19 (61,3%) eram do sexo masculino, aproximadamente metade 17 (54,8%) encontrava-se na faixa etária de 40 a 59 anos, 18 (58,1%) encontravam-se com sobrepeso ou obesidade classes I e II. Quanto aos antecedentes familiares, os dados mais expressivos apontam que 23 (74,2%) apresentavam hipertensão arterial sistêmica, 15 (48,3%) diabetes melittus, 17 (54,8%) infarto agudo do miocárdio e 6 (19,3%) acidente vascular cerebral. Das mulheres entrevistadas, 7 (22,6%) faziam uso algum tipo de terapia de reposição hormonal. No tocante ao estilo de vida relacionado aos hábitos alimentares, 29 (93,6%) utilizavam frituras nas refeições, 14 (45,2%) ingeriam doces e refrigerantes diariamente e 13 (41,9%) tomavam três xícaras ou mais de café ao dia, 18 (58,1%) faziam uso de bebidas alcoólicas, 10 (32,2%) eram fumantes, 9 (29,0%) ex-fumantes e 18 (58,1%) sedentários. Quanto ao estresse, 12 (38,7%) sentiam-se estressados no local de trabalho e 19 (61,3%) dormiam menos que oito horas por noite. Em relação ao sistema de saúde, 16 (51,6%) conheciam o diagnóstico, 12 (38,7%) apresentaram dúvidas acerca da doença, 21 (67,7%) utilizavam os serviços de saúde oferecidos pelo plano de saúde e 17 (54,8%) realizavam tratamento de hipertensão arterial sistêmica e diabetes melittus. Os dados revelam que os pacientes infartados estão expostos a hábitos autocriados que são passiveis de modificação havendo a necessidade de iniciar este processo educativo inclusive no período de internação hospitalar. / The cardiovascular diseases in Brazil, constitute nowadays death’s first cause and myocardial infarction is the most frequent nosological entity amonmg heart isquemical diseases. Among risk factors which predispose people committed by this disease are their life style’s and familiar history’s habits. This descriptive investigation intended to identify the risk factors related to the environment, human biology, life style and health systems of patients admitted in a private hospital, until 48 hours after the myocardial infarction; identify the knowledge’s blanket concerning to the risk factors related to new health problems’ development and verify if some variables are related to the risk factors which are similar to those of admitted patients in private and public hospitals. The theoretical referential used was the Health Model Field which constitutes the elements linked to the environment, human biology, life style an health system. We interviewed 31 internee patients in a private hospital in São Paulo’s interior, from January through July, 2003. Concerning to the environment 93,5% of the patients were literate; among them 11 (35,5%) had completed high school; related to their occupation 10 (32,2%) were retired and housewives; concerning to their working hours and job numbers, 24 (77,4%) work around 8 or 10 hours a day and have only one job; when referring to their familiar monthly income, 19 (61,3%) obtained from 5 to or more minimum salaries; 22 (70,9%) were married and 15 (48,3%) had three or more children; 21 (67,7%) were from Ribeirão Preto and its region and all of them lived in urban areas. When referring to the human biology, 19 (61,3%) were masculine and their ages varied between 40 and 59 years old; 18 (58,1%) were over weighted or fat, belonging to classes I and II; concerned to the familiar preceding, the most expressive data showed that 23 (74,2%) presented systemic arterial hypertension; 15 (48,3%) mellitus diabetes; 17 (54,8%) myocardial infarction and 6 (19,3%) cerebral vascular accident; 7 (22,6%) were feminine and were using hormones. Concerned to their life style, related to the feeding habits, 29 (93,6%) were accustomed to eat fried food; 14 (45,2%) used to eat sweeties and drink soft drinks daily; 13 (41,9%) used to drink 3 or more cups of coffee a day. When referring to the use of alcoholic drinks, 18 (58,1%) used to drink it; 10 (32,2%) were smokers and 9 (29,0%) were ex-smokers; 18 (58,1%) were sedentary. When referring to the stressing environment and sleeping patterns, 12 (38,7%) mention the work place and 19 (61,3%) sleep less than 8 hours a day. Concerning to the health system, 16 (51,6%) knew their diagnosis; 12 (38,7%) presented doubts about their diseases; 21 (67,7%) used the health services offered by their health insurance and 17 (54,8%) were under arterial hypertension and mellitus diabetes treatment. The data showed the patients who suffered by myocardial infarction are exposed to “selfcreated" habits, which may be modified and it is important to mention the necessity of raising educative programs including the patient’s permanence at the hospital.

Like any muscle, cardiac contraction is evoked by action potentials. In the healthy heart, atrial and ventricular activation occur through impulse conduction via the rapid conduction system. Normal cardiac function requires a highly synchronized series of mechanical events occurring in the atria and the ventricles. This synchronization is achieved by rapid conduction of action potentials through the electrical conduction system, which leads to coordinated mechanical activation and deactivation of the myocardium — a process known as electromechanical coupling. As a result of this coordinated electromechanical coupling, the left ventricle functions efficiently as a pump. On the contrary, asynchronous electrical activation leads to asynchronous contraction. The presence of a bundle branch block or other intraventricular conduction delay can worsen heart failure due to systolic dysfunction by causing ventricular dyssynchrony, thereby inducing regional loading disparities and reducing the efficiency of contraction. Consistent with the idea that ventricular dyssynchrony exacerbates left ventricular dysfunction is the observation that a variety of hemodynamic benefits follow the correction of dyssynchrony with cardiac resynchronization therapy (CRT) using biventricular pacing. With decades of research on electromechanical coupling in the heart, it is now recognized that (1) cardiac dyssynchrony worsens ventricular efficiency and contributes to the progression of systolic heart failure; (2) cardiac dyssynchrony can be accurately assessed by echocardiography; (3) cardiac dyssynchrony independently predicts worse prognosis in patients with systolic heart failure; and (4) CRT has established as an effective treatment for systolic heart failure, leading to improved symptomatic status and better survival. / Concerning the subject of cardiac dyssynchrony there are still a lot of unanswered questions which are important to complete understanding of disease mechanisms of heart failure and hence to develop better treatment strategies. First, patients with heart failure but with a preserved ejection fraction (HFPEF) constitutes about half of the heart failure occurrence. Yet, it is not completely understood whether cardiac dyssynchrony, as a potential pathogenic mechanism and therapeutic target, is present in these patients. Second, the heart and circulation is a dynamic system. Nevertheless, scarce data exists on how cardiac dyssynchrony alters in response to exercise and other hemodynamic stressors in patients with heart failure. The potential clinical significance of dynamic dyssynchrony is unknown. Furthermore, identification of precipitating factors of acute hemodynamic decompensation in heart failure is important to prevent recurrent acute exacerbation and hospitalization. Cardiac dyssynchrony has been suspected to be an insidious, potentially correctable trigger of acute decompensated heart failure (ADHF), but scientific evidence is limited. Last but not least, about 30% of the CRT recipients did not respond to the treatment. It was proposed that inadequate optimization of atrioventricular (AV) synchronization is the most common contributory factor, hence the routine practice of AV optimization after CRT implantation. But again, electromechanical coupling is a dynamic process. It is uncertain, however, whether AV optimization should be performed at rest or during exercise to achieve optimal hemodynamic and clinical benefit. / In Part I of this thesis, I will review the literature on heart failure, cardiac dyssynchrony, and exercise impact on the cardiovascular system. In Chapter 1, the definition, clinical classification, and epidemiology of heart failure, as well as the biomechanical model for heart failure progression will be discussed. In Chapter 2, the literature on the normal and pathological electromechanical coupling mechanism, the clinical implication of dyssynchrony in heart failure, and the effect of CRT will be reviewed. In Chapter 3, I will discuss the current understanding of the physiologic effect of exercise, heart rate and stress on cardiac function and synchronicity. In Part II, the hypotheses (Chapter 4) and general objectives (Chapter 5) of the studies included in this thesis will be specified. In Part III, I will describe in detail the general methodology used inthese studies including the study population involved (Chapter 6), the echocardiographic techniques (Chapter 7), and the exercise/pharmacological stress protocols (Chapter 8) used in these studies. / Part IV will be a thorough and logical reporting of the background, methods, findings, discussion, and conclusion of each of the clinical studies of this thesis. Chapter 9, 10 and 11 will focus on patients with preserved ejection fraction and Chapter 12 and 13 will attempt to fill the gap of knowledge of cardiac dyssynchrony in patients with systolic heart failure. / In the study discussed in Chapter 9, the prevalence of left ventricular mechanical dyssynchrony in coronary artery disease with preserved ejection fraction was evaluated. Ninety-four consecutive patients with chronic coronary artery disease and preserved ejection fraction (≥50%) were evaluated using echocardiography with tissue Doppler imaging and compared to 217 patients with depressed ejection fraction and (<50%) and 117 healthy subjects. Left ventricular systolic and diastolic dyssynchrony were determined by measuring the standard deviations of peak systolic (Ts-SD) and early diastolic myocardial (Te-SD) velocities, respectively, using a six-basal/six-mid-segmental model. In patients with coronary artery disease and preserved ejection fraction, both Ts-SD (32.2±17.3 compared with 17.7±8.6 ms; p<0.05) and Te-SD (26.2±13.6 compared with 20.3±8.1 ms; p<0.05) were significantly prolonged when compared with controls, although they were less prolonged than patients with coronary artery disease and depressed ejection fraction (Ts-SD, 37.8±16.5 ms; and Te-SD, 36.0±23.9 ms; both p<0.005). Patients with preserved ejection fraction who had no prior myocardial infarction had Ts-SD (32.9±17.5 ms) and Te-SD (28.6±14.8 ms) prolonged to a similar extent (p=NS) to those with prior myocardial infarction (Ts-SD, 28.4±16.8 ms; and Te-SD, 25.5±15.0 ms). Patients with class III/IV angina or multi-vessel disease were associated with more severe mechanical dyssynchrony (P<0.05). Furthermore, the majority of patients with mechanical dyssynchrony had narrow QRS complexes in those with preserved ejection fraction. This is in contrast with patients with depressed ejection fraction in whom systolic and diastolic dyssynchrony were more commonly associated with wide QRS complexes. / In Chapter 10, focus will be shifted to patients with acute coronary syndrome complicated by acute HFPEF. One hundred two patients presenting with acute coronary syndrome (ejection fraction ≥50%) and 104 healthy controls were studied using tissue Doppler imaging: group 1 (n=55) had HFPEF on presentation and group 2 (n=47) had no clinical HFPEF. Te-SD was found to be greater in group 1 (33±13 ms) than group 2 (21±9 ms) (p<0.001), and diastolic mechanical dyssynchrony was evident in 35% of patients in group 1 but in only 9% in group 2 (p<0.001). Worsening of the diastolic dysfunction grade was associated with a parallel increase in Te-SD (grades 0, 1, 2, and 3: 16±3 ms, 21±5 ms, 28±9 ms, and 41±17 ms, respectively; p<0.001). Te-SD correlated negatively with mean early diastolic basal myocardial velocity (Em) (r=-0.56, p<0.001) and positively with peak mitral inflow velocity of the early rapid-filling wave/Em (r=0.69, p<0.001). Multivariate analysis identified peak mitral inflow velocity of the early rapid-filling wave/Em as the only variable independently associated with HFPEF [odd sratio (OR)=1.48, p=0.001]. When peak mitral inflow velocity of the early rapid-filling wave/Em was excluded from the model, Te-SD (OR=1.13, p<0.001) and mean Em (odds ratio=0.37, p<0.001) became independently associated with HFPEF. / In Chapter 11, I will evaluate the impact of hemodynamic stress on left ventricular dyssynchrony and the relationship and predictive value of dynamic changes of left ventricular dyssynchrony on hypertensive HFPEF. In this study, a total of 131 subjects including 47 hypertensive HFPEF patients, 34 hypertensive patients with left ventricular hypertrophy without HFPEF, and 50 normal controls were studied by dobutamine stress echocardiography with tissue Doppler imaging. In normal controls, systolic and diastolic dyssynchrony did not develop during stress. The prevalence of resting systolic (36.2% vs. 38.2%, p=0.85) and diastolic (34.0% vs. 29.4%, p=0.66) dyssynchrony was similar in patients with HFPEF and left ventricular hypertrophy. During stress, the prevalence of systolic and diastolic dyssynchrony increased dramatically to 85.1% and 87.2%, respectively, in patients with HFPEF, but only 52.9% and 58.8% in patients with left ventricular hypertrophy (p<0.005). In HFPEF group, stress-induced increase in mean systolic basal myocardial velocity (Sm) was significantly blunted (2.8±2.0 vs. 4.2±2.4 cm/s, p=0.004), and the increase was abolished for mean Em (-0.3±2.5 vs. 2.4±3.4 cm/s, p<0.001). On multivariate analysis, stress-induced changes in mean Em (OR=0.69, p=0.004) and mean Sm (OR=0.56, p=0.004), and diastolic (OR=4.6, p=0.005) and systolic dyssynchrony during stress (OR=4.3, p=0.038) were independent determinants for occurrence of HFPEF. / In Chapter 12, the role of dyssynchrony in patients with systolic heart failure presentating with acute decompensation (ADHF) will be studied. In this study, it was hypothesized that acute left ventricular systolic dyssynchrony might be a hidden triggering mechanism for ADHF. Echocardiography with tissue Doppler imaging was performed in 145 subjects with systolic heart failure (ejection fraction <50%), including 84 consecutive patients presented with ADHF requiring hospitalization, comparing them to 61 chronic stable heart failure patients who had no heart failure exacerbation or hospitalization in the past 6 months. The ADHF group was observed to have higher heart rate on admission than patients with stable heart failure (82±15 vs 68±13 bpm, P<0.001), greater left ventricular wall thicknesses and mass (all P<0.05), and mitral regurgitation was more common (71% vs 46%, P<0.0001; ERO=0.12±0.11 vs 0.02±0.04 cm2, P<0.0001), but the overall severity of mitral regurgitation was mild or moderate. Despite no difference in ejection fraction, the ADHF group had significantly lower mean Sm (2.7±0.9 cm/s vs 3.0±0.9 cm/s, P=0.04). The Ts-SD was significantly prolonged in the ADHF group compared to patients with stable heart failure (44.7±16.6 vs 33.4±17.7 ms, P=0.0001). Significant left ventricular systolic dyssynchrony was evident in 75% (63 of 84) of patients of the ADHF group, compared to only 44% (27 of 61) of patients with chronic stable heart failure (P=0.0002). / In Chapter 13, I will focus on the role of dynamic AV dyssynchrony during exercise in patients with systolic heart failure who receive CRT. AV delay in CRT recipients are typically optimised at rest. However, there are limited data on the impact of exercise-induced changes in heart rate on the optimal AV delay and left ventricular function. In this study, AV delays were serially programmed in 41 CRT patients with intrinsic sinus rhythm at rest and during two stages of supine bicycle exercise with heart rates at 20 bpm (stage I) and 40 bpm (stage II) above baseline. The optimal AV delay during exercise was determined by the iterative method to maximise cardiac output using Doppler echocardiography. Results were compared to physiological change in PR intervals in 56 normal controls during treadmill exercise. The optimal AV delay was progressively shortened (p<0.05) with escalating exercise level (baseline: 123±26 ms vs. stage I: 102±24 ms vs stage II: 70±22 ms, p<0.05). AV delay optimisation led to a significantly higher cardiac output than without optimisation did during stage I (6.2±1.2 l/min vs. 5.2±1.2 l/min, p<0.001) and stage II (6.8±1.6 l/min vs. 5.9±1.3 l/min, p<0.001) exercise. A linear inverse relationship existed between optimal AV delays and heart rates in CRT patients (AV delay=241-1.61 x heart rate, R²=0.639, p<0.001) and healthy controls (R²=0.646, p<0.001), but the slope of regression was significantly steeper in CRT patients (p<0.001). / In conclusion, the works included in this thesis provide new evidence that left ventricular mechanical dyssynchrony is common in patients with coronary artery disease and preserved ejection fraction, even in patients without prior myocardial infarction or evidence of eletromechanical delay. In particular, left ventricular diastolic mechanical dyssynchrony may impair diastolic function and contribute to the pathophysiology of HFPEF during acute coronary syndrome. Moreover, dynamic dyssynchrony and impaired myocardial longitudinal function reserve during stress may contribute importantly to the pathophysiology of hypertensive HFPEF. In patients with heart failure and reduced ejection fraction, a high prevalence of left ventricular systolic dyssynchrony during acute decompensation suggests that acute or dynamic left ventricular systolic dyssynchrony may be an important precipitating factor and a potential therapeutic target. Progressive shortening of hemodynamically optimal AV delay with increasing heart rate during exercise suggests that dyssynchrony is dynamic and there may be a need for programming of rate-adaptive AV delay in CRT recipients to optimise clinical response. I believe this work will provide new understanding of the prevalence, mechanism, and clinical significance of cardiac dyssynchrony in heart failure. / Lee, Pui Wai. / Thesis (M.D.))--Chinese University of Hong Kong, 2015. / Includes bibliographical references (leaves 138-174). / Title from PDF title page (viewed on 24, October, 2016).