Impact of obstructive sleep apnea on right ventricular global function: sleep apnea and myocardial performance index

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by repetitive upper airway obstructions during sleep, and it might cause cardiovascular complications such as heart failure, arrhythmias, myocardial infarction, systemic and pulmonary hypertension. OBJECTIVES: To determine right ventricular diameters and myocardial performance index (MPI) reflecting ventricular global function in uncomplicated OSA patients. METHODS: 49 subjects without hypertension, diabetes mellitus, or any cardiac or pulmonary disease referred for evaluation of OSA had overnight polysomnography and complete echocardiographic assessment. According to the apnea-hypopnea index (AHI), subjects were divided into three groups: group 1: control subjects (AHI <5, n = 20), group 2: patients with mild OSA (AHI: 5-14, n = 11), and group 3: moderate-severe OSA (AHI > or = 15, n = 18). Right ventricular free wall diameter was measured by M mode, and right ventricular MPI was calculated as (isovolumic contraction time + isovolumic relaxation time)/pulmonary ejection time. RESULTS: There were no differences of age, body mass index, heart rates, systolic and diastolic blood pressures among the groups (p > 0.05). Right ventricular end-diastolic and end-systolic diameters were not statistically different between the groups, and were within normal limits. Also, right ventricular free wall diameter was not significantly different between the groups of control, mild OSA and moderate-severe OSA (6.7 +/- 0.9, 6.9 +/- 1.0, 7.1 +/- 1.1 mm, p > 0.05). Right ventricular diastolic dysfunction was shown only in group 3 patients. Right ventricular MPI was statistically higher in group 3 (0.62 +/- 0.18) than in group 2 patients (0.50 +/- 0.10), and group 1 patients (0.48 +/- 0.08, p < 0.001). CONCLUSIONS: It was suggested that patients with moderate-severe OSA had a right ventricular global dysfunction, in addition to the presence of a diastolic dysfunction.     

Arterial hypertension and chronic heart failure

Arterial hypertension, alone or in combination with ischemic heart disease, precedes the development of heart failure. The Framingham study demonstrated that hypertension was the major risk factor in the development of heart failure. Arterial hypertension is not a sole factor contributing to the development of heart failure. The syndrome of heart failure is a consequence of multiple systemic responses and the development of heart failure is a complex and progressive process associated with cardiovascular disease resulting from risk factors: hypertension, obesity, smoking and dyslipidaemia. Arterial hypertension is the main precursor of left ventricular hypertrophy. Initially, this process causes diastolic dysfunction in the early stages of primary hypertension. Systolic dysfunction is rarely observed in those subjects. Left ventricular hypertrophy is also an important risk factor for myocardial infarction and ventricular arrhythmias. Asymptomatic systolic and diastolic left ventricular dysfunction may both progress to overt HFThe primary prevention of heart failure patients should be based upon strategies providing tight and sustained blood pressure control. This therapy should include an agent that inhibits the renin–angiotensin–aldosterone system. Treatment of arterial hypertension in patients with HF must take into account the prevalent type of cardiac dysfunction—diastolic or systolic.     

Left ventricular diastolic dysfunction: risks, identification, and treatment

Risk factors of cardiovascular disease, such as hypertension, diabetes, and myocardial infarction, if left untreated, will increase the risk of the development of chronic heart failure. Much is known about the pathophysiology and effective treatments of chronic heart failure from left ventricular systolic dysfunction; however, little clinical trial evidence exists concerning benefits of treating patients with chronic heart failure and preserved systolic function, also known as left ventricular diastolic dysfunction. Rather, an understanding of the pathophysiology and patient signs and symptoms has usually dictated choice of treatments. With the results of ongoing trials, as well as the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM)-Preserved and the Digitalis Investigation Group (DIG) trials, clinical evidence is accumulating to support effective treatments in patients with left ventricular diastolic dysfunction. The focus of this review is to discuss the risks of, identification of, and rationale for therapeutic choices being employed for treating left ventricular diastolic dysfunction and implications from studies that may support these choices.     

Obstructive sleep apnoea and cardiovascular disease

Obstructive sleep apnoea (OSA) leads to both acute and chronic physiological effects on the cardiovascular system. There is now a large amount of evidence showing that OSA is independently associated with a wide spectrum of clinical cardiovascular disease (CVD). Evidence for a causative effect of OSA is strongest for hypertension, but is weaker for other cardiovascular disorders. Large prospective trials are ongoing and when results become available the link between OSA and CVD is likely to be strengthened. Treatment of OSA with continuous positive airway pressure has been shown to improve blood pressure, particularly in those with hypertension, and also left ventricular ejection fraction in those with congestive heart failure. Given the high prevalence of OSA in the community and its effects on the cardiovascular system, symptoms of this disorder should be sought in patients being investigated or treated for CVD.     

Clinical Characteristics,Left and Right Ventricular Ejection Fraction,and Long-term Prognosis in Patients with Non-insulin-dependent Diabetes Surviving an Acute Myocardial Infarction

Patients with diabetes mellitus have a high morbidity and mortality from acute myocardial infarction, the reason for which is not fully understood. The relationship between congestive heart failure symptoms, left ventricular ejection fraction, and long-term mortality was examined in 578 hospital survivors of acute myocardial infarction, 47 of whom had Type 2 (non-insulin-dependent) diabetes mellitus. None of the patients were treated with insulin. The prevalence of congestive heart failure during hospitalization was similar in patients with and without diabetes, although mean diuretic dose was higher in the former patients. Left and right ventricular ejection fraction was measured with radionuclide ventriculography in the second week after acute myocardial infarction. At discharge from the coronary care unit, patients with and without diabetes had similar left ventricular ejection fraction (with diabetes: median 46% vs without diabetes: median 43%; p = 0.89). Median right ventricular ejection fraction (62 %) was within normal limits in both groups and did not differ statistically. Survival data were obtained for all patients. The 5-year mortality was increased in patients with diabetes compared with non-diabetic patients independent of left ventricular ejection fraction. Univariate analysis showed that the cumulative 5-year mortality rate was 53 % in the group with diabetes compared with 43% in the non-diabetic group (p = 0.007). Using multivariate regression analysis presence of diabetes was found to have a significant association with long-term mortality after myocardial infarction, that was independent of age, history of hypertension, congestive heart failure symptoms during hospitalization or of either left or right ventricular ejection fractions at discharge. We conclude that the excess mortality in patients with non-insulin-dependent diabetes mellitus is not explained by available risk markers after myocardial infarction. Even though left ventricular ejection fraction and serum creatinine did not differ significantly, the apparent higher dose of Frusemide in patients with than without non-insulin-dependent diabetes mellitus might indicate that heart failure, if present, is more severe in patients with than in those without diabetes. The importance of diastolic dysfunction in this context needs to be determined.     

From left ventricular hypertrophy to congestive heart failure: management of hypertensive heart disease

Other than age, left ventricular hypertrophy (LVH) is the most potent predictor of adverse cardiovascular outcomes in the hypertensive population, and is an independent risk factor for coronary heart disease, sudden death, heart failure and stroke. Although directly related to systolic blood pressure, other factors including age, sex, race, body mass index and stimulation of the renin-angiotensin-aldosterone and sympathetic nervous systems play an important role in the pathogenesis of LVH. LVH involves changes in myocardial tissue architecture consisting of perivascular and myocardial fibrosis and medial thickening of intramyocardial coronary arteries, in addition to myocyte hypertrophy. The physiologic alterations which occur as a result of these anatomical changes include disturbances of myocardial blood flow, the development of an arrhythmogenic myocardial substrate and diastolic dysfunction. The latter is directly related to the degree of myocardial fibrosis and is the hemodynamic hallmark of hypertensive heart disease. When diastolic dysfunction is present, left ventricular end-diastolic pressure increases out-of-proportion to volume and may be elevated at rest or with exertion leading to clinical heart failure. At least one third of heart failure patients in the United States can be considered to have heart failure related to diastolic dysfunction. Compared to heart failure patients with systolic dysfunction, diastolic heart failure patients are more likely to be older, female, and to be hypertensive at the time of presentation. Although it has been assumed that LVH may lead to systolic dysfunction, evidence is lacking that LVH resulting from hypertension is a major risk factor for systolic heart failure independent of coronary artery disease. Treatment of hypertension greatly attenuates the development of LVH and significantly decreases the incidence of heart failure. In patients with established LVH, regression is both possible and desirable and results in a significant reduction in adverse clinical endpoints.     

Arterial hypertension and systolic left ventricular dysfunction: therapeutic approach

Arterial hypertension is a cardinal precursor of congestive heart failure, and diastolic dysfunction is the most frequent mechanism for it. Systolic left ventricular dysfunction, although less frequent, has a worse prognosis. Most cases of systolic dysfunction in patients with hypertension is due to acute myocardial infarction, although other mechanisms can be involved. In some studies, non-ischemic hypertensive systolic dysfunction is the etiology of chronic heart failure in up to 10% of patients with dilated cardiomyopathy. Diastolic dysfunction and left ventricular hypertrophy are also associated with a higher risk of heart failure and systolic dysfunction. Given the poor prognosis of patients with congestive heart failure and dilated cardiomyopathy, it is fundamental to try to prevent the development of left ventricular dysfunction by means of a correct control of blood pressure, regression of left ventricular hypertrophy and prevention of coronary artery disease. When systolic dysfunction is established, angiotensin converting enzyme inhibitors are the treatment of choice; diuretics and digoxin can be added in patients with overt congestive heart failure. Recent studies suggest that other drugs, such as carvedilol and losartan, can be beneficial, but current evidence is still scarce.     

Obstructive sleep apnea syndrome and cardiovascular diseases

Obstructive sleep apnea syndrome (OSAS) is a chronic disease characterized by recurrent episodes of partial or complete upper airway collapse and obstruction during sleep, associated with intermittent oxygen desaturation, sleep fragmentation, and symptoms of disruptive snoring and daytime sleepiness. Increasing focus is being placed on the relationship between OSAS and all-cause and cardiovascular disease-related mortality, but it still largely unclear whether this association is causative or simply speculative and epidemiological. Basically, reliable clinical evidence supports the hypothesis that OSAS might be associated with essential and resistant hypertension, as well as with an incremental risk of developing stroke, cardiac rhythm perturbations (e.g., atrial fibrillation, bradyarrhythmias, supraventricular and ventricular arrhythmias), coronary artery disease, acute myocardial infarction, and heart failure. Although it is still unclear whether OSAS might represent an independent risk factor for several acute or chronic conditions, or rather might trigger cardiovascular disease in the presence of traditional cardiovascular risk factors (e.g., obesity, diabetes, and dyslipidemia), there is a plausible biological background underlying this association, in that most of the mechanisms implicated in the pathogenesis of OSAS (i.e., hypoxia, hypercapnia, negative intrathoracic pressure, micro-arousal, sympathetic hyperactivity, metabolic and hormonal changes, oxidative stress, phlogosis, endothelial dysfunction, hypercoagulability, and genetic predisposition) might also be involved in the pathogenesis of cardiovascular disorders. In this article we discuss the different aspects of the relationship between OSAS and pathogenically different conditions such as systemic hypertension, coronary artery disease, stroke, metabolic abnormalities, arrhythmias, and heart failure, and we also discuss the kaleidoscope of phenomena implicated in the pathogenesis of this challenging disease.     

Sleep disorders in patients with congestive heart failure

PURPOSE OF REVIEW: This review of recent literature pertains to the growing evidence that obstructive sleep apnea contributes to the development of systemic hypertension and congestive heart failure. RECENT FINDINGS: There is irrefutable evidence that OSA causes systemic hypertension and that continuous positive airway pressure (CPAP) treatment of OSA causes a reduction in blood pressure. Moreover there is evidence that untreated OSA is associated with left ventricular diastolic and systolic failure and that treatment with CPAP improves systolic function. SUMMARY: OSA should be considered in patients with systemic hypertension or heart failure.     

Ventricular function in snorers and patients with obstructive sleep apnea.

We hypothesized that intermittent hypoxemia and increased ventricular afterload due to obstructive apnea during sleep (OSA) would cause chronic left ventricular dysfunction. Overnight polysomnography, M-mode and two-dimensional echo-Doppler studies while awake were performed on 51 consecutive snorers, 30 with OSA and 21 without apnea. Patients with previous myocardial infarction, awake hypoxemia or hypercapnia, or other causes of nocturnal hypoxemia were excluded. Echo-Doppler measurements included end-diastolic right and left ventricular dimensions and wall thickness, indices of left ventricular systolic performance (fractional shortening, ejection fraction and ejection time and diastolic performance, (isovolumic relaxation time, ratio of peak early [E] to late [A] diastolic transmitral flow and mitral pressure half-time). Both OSA patients and nonapneic snorers were of similar age. Although OSA patients were heavier, had a greater apnea-hypopnea index, and significant nocturnal hypoxemia, their echo-Doppler measurements were within normal limits and were not significantly different from nonapneic snorers. It is concluded that isolated obstructive sleep apnea does not cause chronic left ventricular dysfunction.     

Cardiac dysfunction induced by novel targeted anticancer therapy: An emerging issue

Increasing use of targeted anticancer agents that inhibit tyrosine kinase signaling (monoclonal antibodies or tyrosine kinase inhibitors) has dramatically improved the survival of patients with malignancies. However, cardiotoxicity, including heart failure, left ventricular dysfunction, hypertension, myocardial infarction, and thromboembolism, has occurred. Importantly, these cardiotoxicities are at least partially reversible and responsive to medical management. Early recognition of cardiovascular side effects is vital to allow long-term, continuous therapy with these life-prolonging agents. This article reviews potential cardiovascular side effects of frequently used inhibitors of tyrosine kinase activity (eg, trastuzumab, sunitinib) and discusses the diagnosis and management of cardiotoxicity associated with targeted therapy.     

血管紧张素转换酶抑制剂对无左心室功能不全的冠心病患者预后的影响

目的采用meta分析评价长期应用血管紧张素转换酶抑制剂(ACEI)是否减少无左心室功能不全的冠心病患者主要心血管事件的发生风险。方法检索MEDLINE、EMBASE数据库、IPA数据库、Cochrane图书馆。检索词:angiotensin-converting enzyme inhibitors,coronary artery disease,coronary heart disease randomi(s)zed controlled trials,clinical trials,myocardial infarction。入选试验满足条件:试验为随机对照试验,研究对象为无左心室功能不全的冠心病患者,随访时间不少于2年。在检索到的文章中共有7个试验(HOPE、PART-2、QUIET、EOROPA、PEACE、CAMELOT、IMAGINE)满足条件,总计36 053例患者。采用比值比OR和95%置信区间(CI)作为评价ACEI和安慰剂治疗差异有无统计学意义的指标。应用RevMan5.0软件行统计学分析。结果采用ACEI治疗可明显减少总病死率(OR=0.86,95%CI为0.80～0.94)、心血管病死率(OR=0.82,95%CI为0.74～0.91)、非致死性心肌梗死的发生率(OR=0.85,95%CI为0.76～0.95)及脑卒中或短暂性脑缺血发作的发生率(OR=0.78,95%CI为0.67～0.91),其他事件如心脏停搏后复苏、血管成形术、心力衰竭入院等发生率也减少。结论 ACEI可明显降低无左心室功能不全的冠心病患者的总病死率和心血管事件发生率。     

Congestive heart failure with preserved left ventricular systolic function after acute myocardial infarction: clinical and prognostic implications

AIMS: To characterise the prevalence, in-hospital complications, management, and long-term outcome of patients with congestive heart failure but preserved left ventricular systolic function after acute myocardial infarction. METHODS: 3166 consecutive patients screened for entry in the Bucindolol Evaluation in Acute Myocardial Infarction Trial with definite acute myocardial infarction and echocardiographic assessment of left ventricular systolic function were included between 1998 and 1999 in this prospective observational study. Main outcome measures were occurrences of in-hospital complications and all cause mortality. RESULTS: Congestive heart failure was seen during hospitalisation in 1464 patients (46%), 717 patients had preserved left ventricular systolic function (wall motion index > or =1.3 corresponding to ejection fraction > or =0.40), and 732 patients had systolic dysfunction (wall motion index <1.3). One year mortality in patients with no heart failure, heart failure with preserved systolic function, and heart failure with systolic dysfunction were 6, 22 and 35%, P<0.0001. Unadjusted risk of death from all causes associated with heart failure and preserved systolic function was 3.3 (95% CI 2.8-4.0), and after adjustment for baseline characteristics and left ventricular systolic function in multivariate Cox proportional hazards analysis the risk was 2.1 (95% CI 1.7-2.6), P<0.0001. CONCLUSIONS: Congestive heart failure is frequently present in patients with preserved left ventricular systolic function, and is associated with increased risk of in-hospital complications and death following acute myocardial infarction.     

Study of left ventricular diastolic function using pulsed Doppler in myocardial infarct in hypertensive subjects

To determine if impairment of left ventricular filling is influenced by acute myocardial infarction in patients with arterial hypertension, left ventricular diastolic function was assessed by pulsed doppler echocardiography in 46 patients (pts) subdivided into four groups (Gr): G.1 (n = 12 pts) with acute myocardial infarction and hypertensive heart disease. G.2 (n = 12 pts) acute myocardial infarction without arterial hypertension. G.3 (n = 10 pts) arterial hypertension without history of coronary artery disease. G.4 (n = 12 pts) healthy subjects. Coronary angiography and left ventricular cineangiogram was performed in 24 pts (G.1 + G.2). Peak mitral flow velocity (cm/s) in early diastole (E), atrial systole (A), A/E and int A/int E ratios were measured by pulsed doppler. Age and heart rate were statistically similar in all groups. No difference was found among G.1 and G.2 in ejection fraction, and left ventricular segmental kinetic. (tables; see text) Conclusion left ventricular filling is impaired in pts with arterial hypertension and in pts with acute myocardial infarction; acute myocardial infarction increase the impairment of left ventricular diastolic function in pts with hypertensive heart disease.     

Tissue Doppler imaging a new prognosticator for cardiovascular diseases.

Tissue Doppler imaging (TDI) is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular (LV) systolic and diastolic function. Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as heart failure, acute myocardial infarction, and hypertension. In these conditions, myocardial mitral annular or basal segmental (Sm) systolic and early diastolic (Ea or Em) velocities have been shown to predict mortality or cardiovascular events. In particular, those with reduced Sm or Em values of <3 cm/s have a very poor prognosis. In heart failure and after myocardial infarction, noninvasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/Ea or E/Em) is a strong prognosticator, especially when E/Ea is > or =15. In addition, systolic intraventricular dyssynchrony measured by segmental analysis of myocardial velocities is another independent predictor of adverse clinical outcome in heart failure subjects, even when the QRS duration is normal. In heart failure patients who received cardiac resynchronization therapy, the presence of systolic dyssynchrony at baseline is associated with favorable LV remodeling, which in turn predicts a favorable long-term clinical outcome. Finally, TDI and derived deformation parameters improve prognostic assessment during dobutamine stress echocardiography. A high mean Sm value in the basal segments of patients with suspected coronary artery disease is associated with lower mortality rate or myocardial infarction and is superior to the wall motion score.     

From Hypertension to Heart Failure

The prevalence of heart failure is increasing in modern societies. Hypertension is a major contributor to the development of heart failure, whether through the development of left ventricular hypertrophy and diastolic dysfunction or by promoting atherosclerosis and myocardial infarction, which eventually leads to systolic dysfunction and left ventricular dysfunction. Effective therapy for hypertension can prevent more than 50% of heart failure events. Most studies done in the last three decades have used β blockers with diuretics as the modality of therapy. These agents have been shown to effectively prevent the development of heart failure. More recent comparative studies have shown that use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are also effective in preventing heart failure. Calcium channel blockers, however, seem to be less effective in preventing development of heart failure in patients with hypertension. It needs to be emphasized that the most important variable in preventing heart failure is the appropriate treatment of hypertension.     

Tissue Doppler imaging a new prognosticator for cardiovascular diseases

Tissue Doppler imaging (TDI) is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular (LV) systolic and diastolic function. Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as heart failure, acute myocardial infarction, and hypertension. In these conditions, myocardial mitral annular or basal segmental (Sm) systolic and early diastolic (Ea or Em) velocities have been shown to predict mortality or cardiovascular events. In particular, those with reduced Sm or Em values of <3 cm/s have a very poor prognosis. In heart failure and after myocardial infarction, noninvasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/Ea or E/Em) is a strong prognosticator, especially when E/Ea is > or =15. In addition, systolic intraventricular dyssynchrony measured by segmental analysis of myocardial velocities is another independent predictor of adverse clinical outcome in heart failure subjects, even when the QRS duration is normal. In heart failure patients who received cardiac resynchronization therapy, the presence of systolic dyssynchrony at baseline is associated with favorable LV remodeling, which in turn predicts a favorable long-term clinical outcome. Finally, TDI and derived deformation parameters improve prognostic assessment during dobutamine stress echocardiography. A high mean Sm value in the basal segments of patients with suspected coronary artery disease is associated with lower mortality rate or myocardial infarction and is superior to the wall motion score.     

Effect of aldosterone blockade in patients with systolic left ventricular dysfunction: implications of the RALES and EPHESUS studies

Aldosterone blockade has been shown to be effective in reducing total mortality as well as hospitalization for heart failure in patients with systolic left ventricular dysfunction (SLVD) due to chronic heart failure and in patients with SLVD post acute myocardial infarction. The evidence for the effectiveness of aldosterone blockade in chronic heart failure comes from the randomized aldactone evaluation study (RALES) while that for patients post infarction from the eplerenone post acute myocardial infarction efficacy and survival study (EPHESUS). These studies suggest that mineralocorticoid receptor activation remains important despite the use of an angiotensin converting enzyme-inhibitor/angiotensin receptor blocking (ARB) agent and a beta blocker. Increasing evidence suggest that aldosterone blockade has important effects not only on the kidney but on ventricular remodeling, myocardial fibrosis, autonomic balance, fibrinolysis, oxidative stress, and activation of the NF-kappaB and AP-1 signaling pathways. The results of these studies in patients with SLVD has important implications not only for patients with chronic heart failure and post infarction but also for the therapy of patients with essential hypertension and other cardiovascular diseases.     

Obstructive sleep apnea as a risk marker in coronary artery disease

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with a range of cardiovascular sequelae and increased cardiovascular mortality. The aim of our study was to assess the prevalence of OSA in patients with symptomatic angina and angiographically verified coronary artery disease (CAD). In addition, we analyzed the association of OSA and other coronary risk factors with CAD and myocardial infarction. METHODS: Overnight non-laboratory-monitoring-system recordings for detection of OSA was performed in 223 male patients with angiographically verified CAD and in 66 male patients with exclusion of CAD. A logistic regression analysis was performed to assess associations between risk factors and CAD and myocardial infarction. RESULTS: CAD patients were found to have OSA in 30.5%, whereas OSA was found in control subjects in 19.7%. The mean apnea/hypopnea index (AHI) was significantly higher (p < 0.01) in CAD patients (9.9 +/- 11.8) than in control subjects (6.7 +/- 7.3). Body-mass-index (BMI) was significantly higher in patients with CAD and OSA than in patients with CAD without OSA (28. 1 vs. 26.7 kg/m(2); p < 0.001). No significant difference was found with regard to other risk factors and left ventricular ejection fraction (LVEF) between both groups. Hyperlipidemia (OR 2.3; CI 1. 3-3.9; p < 0.005) and OSA defined as AHI >/=20 (OR 2.0; CI 1.0-3.8, p < 0.05) were independently associated with myocardial infarction. CONCLUSIONS: There is a high prevalence of OSA among patients with angiographically proven CAD. OSA of moderate severity (AHI >/=20) is independently associated with myocardial infarction. Thus, in the care of patients with CAD, particular vigilance for OSA is important.