Left ventricular response to continuous positive airway pressure: role of left ventricular geometry.

BACKGROUND: Continuous positive airway pressure (CPAP) may be a useful adjunct in patients with congestive heart failure. OBJECTIVES: To evaluate the relationship between left ventricular geometry and hemodynamic response to CPAP. METHODS: Right heart catheter studies were performed in 26 patients before, during and after application of CPAP (8 cm H(2)O) over 15 min. Response to therapy was defined as an increase in stroke volume using CPAP. RESULTS: Cardiac output decreased from 6.9 +/- 1.9 to 6.2 +/- 1.4 liters/min (p = 0.01) with a slight increase after cessation of CPAP (not significant). There was no significant change in stroke volume (92 +/- 34 vs. 90 +/- 31 ml, p = 0.584) or pulmonary capillary wedge pressure (14.7 +/- 7.0 vs. 14.2 +/- 6.5 mm Hg, p = 0.26). There was a correlation between hemodynamic effects of CPAP therapy and left ventricular end-diastolic volume (r = 0.515, p = 0.01), mass-volume ratio (r = -0.41, p = 0.04) and pulmonary capillary wedge pressure (r = 0.654, p = 0.001) at baseline. Half the patients (n = 13) were categorized as responders with an average increase in stroke volume of 11.5 +/- 2.1%. Responders showed significantly higher left ventricular end-diastolic volume, pulmonary capillary wedge pressure and lower mass-volume ratio. CONCLUSION: Patients with high pulmonary capillary wedge pressure, elevated end-diastolic volumes and a low left ventricular mass-volume ratio might profit from CPAP therapy.

Impact of obstructive sleep apnea on the occurrence of restenosis after elective percutaneous coronary intervention in ischemic heart disease.

RATIONALE: There is growing evidence that obstructive sleep apnea is associated with coronary artery disease. However, there are no data on the course of coronary stenosis after percutaneous coronary intervention in patients with obstructive sleep apnea. OBJECTIVES: To determine whether sleep apnea is associated with increased late lumen loss and restenosis after percutaneous coronary intervention. METHODS: 78 patients with coronary artery disease who underwent elective percutaneous coronary intervention were divided in 2 groups: 43 patients with an apnea hypopnea - Index < 10/h (group I) and 35 pt. with obstructive sleep apnea and an AHI > 10/h (group II). Late lumen loss, a marker of restenosis, was determined using quantitative coronary angiography after 6.9 +/- 3.1 months. MAIN RESULTS: Angiographic restenosis (>50% luminal diameter), was present in 6 (14%) of group I and in 9 (25%) of group II (p = 0.11). Late lumen loss was significant higher in pt. with an AHI > 10/h (0.7 +/- 0.69 mm vs. 0.38 +/- 0.37 mm, p = 0.01). Among these 35 patients, 21(60%) used their CPAP devices regularly. There was a marginally lower late lumen loss in treated patients, nevertheless, this difference did not reach statistical significance (0.57 +/- 0.47 mm vs. 0.99 +/- 0.86 mm, p = 0.08). There was no difference in late lumen loss between treated patients and the group I (p = 0.206). CONCLUSION: In summary, patients with OSA and coronary artery disease have a higher degree of late lumen loss, which is a marker of restenosis and vessel remodeling after elective percutaneous intervention.

The potential benefits of treatment of sleep apnea in heart failure.

At least half of patients with heart failure (HF) suffer from sleep apnea. Growing evidence suggests that there may be a strong pathophysiological link between chronic HF and sleep apnea due to nocturnal oxygen desaturation and sympathetic activation. It seems that sleep apnea contributes to systolic and diastolic HF, reduced left and right ventricular function, and arrhythmia (e.g. atrial fibrillation, bradycardia, or ventricular ectopy). Therefore, treatment of sleep apnea might alleviate cardiac symptoms and improve cardiac function. Nevertheless, the exact role of long-term treatment of sleep apnea in HF patients remains to be elucidated, as important clinical endpoints (e.g mortality) have been assessed in only a few studies. Heart Fail Monit 2008;5(4):106-11.

Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials.

OBJECTIVES: We aimed to perform a meta-analysis of clinical trials on intracoronary cell therapy after acute myocardial infarction (AMI). BACKGROUND: Intracoronary cell therapy continues to be evaluated in the setting of AMI with variable impact on left ventricular ejection fraction (LVEF). METHODS: We searched the CENTRAL, mRCT, and PubMed databases for controlled trials reporting on intracoronary cell therapy performed in patients with a recent AMI (< or =14 days), revascularized percutaneously, with follow-up of > or =3 months. The primary end point was change in LVEF, and secondary end points were changes in infarct size, cardiac dimensions, and dichotomous clinical outcomes. RESULTS: Ten studies were retrieved (698 patients, median follow-up 6 months), and pooling was performed with random effect. Subjects that received intracoronary cell therapy had a significant improvement in LVEF (3.0% increase [95% confidence interval (CI) 1.9 to 4.1]; p < 0.001), as well as a reduction in infarct size (-5.6% [95% CI -8.7 to -2.5]; p < 0.001) and end-systolic volume (-7.4 ml [95% CI -12.2 to -2.7]; p = 0.002), and a trend toward reduced end-diastolic volume (-4.6 ml [95% CI -10.4 to 1.1]; p = 0.11). Intracoronary cell therapy was also associated with a nominally significant reduction in recurrent AMI (p = 0.04) and with trends toward reduced death, rehospitalization for heart failure, and repeat revascularization. Meta-regression suggested the existence of a dose-response association between injected cell volume and LVEF change (p = 0.066). CONCLUSIONS: Intracoronary cell therapy following percutaneous coronary intervention for AMI appears to provide statistically and clinically relevant benefits on cardiac function and remodeling. These data confirm the beneficial impact of this novel therapy and support further multicenter randomized trials targeted to address the impact of intracoronary cell therapy on overall and event-free long-term survival.

Prevalence of paroxysmal atrial fibrillation depending on the regression of left ventricular hypertrophy in arterial hypertension.

Arterial hypertension (HTN) represents one of the major causes of atrial fibrillation, a cardiac arrhythmia with high prevalence and comorbidity. The aim of this study was to investigate whether paroxysmal atrial fibrillation can be treated by the regression of left ventricular hypertrophy achieved by antihypertensive therapy. Included in the present study were 104 patients who had had HTN for more than 1 year. None of them suffered from coronary heart disease. All patients were investigated by 24-h Holter ECG and echocardiography at baseline and after a mean of 24 months. Patients were divided into two groups: group A consisted of those (53.8%) who showed a regression of the left ventricular muscle mass index (LVMMI) during the follow-up (154.9+/-5.1 vs. 123.5+/-2.8 g/m(2)), and group B those (45.2%) who showed a progression of LVMMI (122.2+/-3.2 vs. 143.2+/-3.2 g/m(2)). In group A the prevalence of atrial fibrillation decreased from 12.5% to 1.8% (p<0.05), while it was increased in group B from 8.5% to 17.0%. The left atrial diameter was reduced following antihypertensive therapy in group A from 39.1+/-5.3 mm to 37.4+/-4.6 mm (p<0.01) and increased in group B from 37.0+/-0.7 mm to 39.0+/-0.9 mm (p<0.01). We conclude that a regression of the left ventricular muscle mass leads to a reduction of left atrial diameter and consecutively to a decrease in the prevalence of intermittent atrial fibrillation. This may be explained by a better left ventricular diastolic function following decreased vascular and extravascular resistance of the coronary arteries. This relation shows the benefits of causal antihypertensive therapy for the treatment of paroxysmal atrial fibrillation.

[Hypertension and heart]. / Hochdruck und Herz.

The term hypertensive heart disease covers the entities left ventricular hypertrophy, microangiopathy, diastolic and systolic dysfunction, und increased risk of arrhythmias. From the pathophysiological point of view this is caused by hypertrophy of cardiac myocytes, interstitial fibrosis and media hypertrophy of the arterioles. As an earliest sign of hypertensive heart disease a microangiopathy can be diagnosed. Also a diastolic dysfunction can be found as an early change. In further persisting arterial hypertension left ventricular hypertrophy develops (often asymmetric), and later a systolic dysfunction. Clinically, the patients suffer from angina pectoris, dyspnea and rhythm disorders. Left ventricular hypertrophy is associated with an increased risk of ventricular malignant arrhythmias. Thus, the main therapeutic principle should be antihypertensive therapy with the goal of regression of hypertrophy and, as a consequence, a decreased mortality risk.

[Chemoreflexsensitivity is reduced in obstructive sleep apnea and might be modulated by the autonomic system]. / Eingeschränkte Chemoreflexsensitivität als Ausdruck einer erhöhten adrenergen Aktivierung bei obstruktiver Schlafapnoe.

BACKGROUND: Chemoreflexes are important mechanisms for regulating ventilatory and cardiovascular function, which are supposed to be influenced in obstructive sleep apnea (OSA). PATIENTS AND METHODS: For determination of chemoreflexsensitivity (CHRS) the ratio of the RR-interval shift in the surface ECG during 5 min inhalation of oxygen via a nose mask was formed in 15 patients with suspected OSA. Noradrenaline plasma concentrations were measured and were correlated to CHRS. RESULTS: Patients with OSA showed a reduced CHRS. CHRS was correlated to the severity of sleep apnea (respiratory disturbance index [RDI]; r = -0.622; p = 0.013), and to minimal nocturnal oxygen saturation (r = 0.594; p = 0.032). Reduced CHRS was associated with higher noradrenaline concentrations (r = -0.542; p = 0.037). CONCLUSION: CHRS is reduced in patients with OSA and correlates with the severity of OSA. Further on, CHRS might be modulated by the autonomic system. Therefore, the determination of CHRS enables to estimate sympathetic activation in these patients.

Stem cell therapy in postinfarction chronic coronary heart disease.

After acute myocardial infarction, bone-marrow-derived cells (BMDCs) improve cardiac function; it is conceivable, but not yet demonstrated, that BMDC therapy might also be useful in chronic infarction. We treated 18 consecutive patients who had chronic myocardial infarction (between 5 months and 8.5 years postinfarction) using intracoronary transplantation of autologous BMDCs and compared this group with a representative control group who did not receive cell therapy. After 3 months, infarct size in the transplantation group was reduced by 30% and both global left ventricular ejection fraction and infarction wall-movement velocity were increased significantly (15% and 57%, respectively), whereas in the control group no significant changes were observed. After transplantation of BMDCs, there was an 11% improvement in maximum oxygen uptake and a 15% increase in regional (18)F-fluordeoxyglucose uptake into infarcted tissue, as determined by positron emission tomography. These results show that functional and metabolic regeneration of infarcted and chronically avital tissue can be achieved in humans using transplantation of bone-marrow-derived cells.

Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study.

OBJECTIVES: Stem cell therapy may be useful in chronic myocardial infarction (MI); this is conceivable, but not yet demonstrated in humans. BACKGROUND: After acute MI, bone marrow-derived cells improve cardiac function. METHODS: We treated 18 consecutive patients with chronic MI (5 months to 8.5 years old) by the intracoronary transplantation of autologous bone marrow mononuclear cells and compared them with a representative control group without cell therapy. RESULTS: After three months, in the transplantation group, infarct size was reduced by 30% and global left ventricular ejection fraction (+15%) and infarction wall movement velocity (+57%) increased significantly, whereas in the control group no significant changes were observed in infarct size, left ventricular ejection fraction, or wall movement velocity of infarcted area. Percutaneous transluminal coronary angioplasty alone had no effect on left ventricular function. After bone marrow cell transplantation, there was an improvement of maximum oxygen uptake (VO2max, +11%) and of regional 18F-fluor-desoxy-glucose uptake into infarct tissue (+15%). CONCLUSIONS: These results demonstrate that functional and metabolic regeneration of infarcted and chronically avital tissue can be realized in humans by bone marrow mononuclear cell transplantation.

Altered blood rheology in obstructive sleep apnea as a mediator of cardiovascular risk.

BACKGROUND: Cardiovascular complications are common in patients with obstructive sleep apnea (OSA). Blood rheology is a major determent of coagulation and an established risk factor for cardiovascular events. Since nocturnal hypoxemia could influence parameters of blood rheology, we hypothesized that OSA alters blood rheology independent of other cardiovascular risk factors. METHODS: One hundred and ten consecutive patients admitted to the sleep laboratory were included. The association of plasma fibrinogen and viscosity (as parameters of blood rheology) with OSA was evaluated. RESULTS: One hundred and ten patients aged 61.4+/-10.1 years (body mass index 28.4+/-4.1 kg/m2) were included. OSA was confirmed in 63 patients (57.2%) with an apnea-hypopnea index (AHI) of 28.7+/-14.9 events/hour. Patients with OSA showed higher levels of plasma viscosity (1.36+/-0.09 vs. 1.31+/-0.08 mPas, p=0.005). Nevertheless, hypertensive apneics have even higher levels of plasma viscosity than nonapneics (1.38+/-0.091 vs. 1.32+/-0.028 mPas, p=0.018). Similar results were found in patients with coronary artery disease, where OSA was associated with elevated plasma viscosity (1.36+/-0.076 vs. 1.31+/-0.081 mPas, p=0.007). Plasma fibrinogen was correlated with nocturnal minimal oxygen saturation (r=-0275, p=0.0036) and AHI (r=0.297, p=0.001). OSA was associated with higher plasma fibrinogen (353+/-83 vs. 317+/-62 mg/dl, p=0.015). These differences persist with control for cardiovascular risk factors. CONCLUSIONS: Patients with OSA have elevated morning fibrinogen levels and a higher plasma viscosity, which correlate positively with indices of sleep apnea severity. These changes in blood rheology are independent of cardiovascular risk factors, and therefore, might be specific mechanisms of OSA. This supports the pathophysiological concept that sleep apnea is a cardiovascular risk factor.

Reduction of peripheral flow reserve impairs endothelial function in conduit arteries of patients with essential hypertension.

BACKGROUND: A diminished flow reserve in resistance vessels is a hallmark of hypertensive microvascular disease. Hypertension is associated with structural alterations in the microcirculation and a reduced endothelium-dependent dilation in conduit arteries. Both have been demonstrated to predict future cardiovascular events. OBJECTIVE: We hypothesized that a reduced peripheral flow reserve impairs endothelial function in upstream conduit arteries in patients with arterial hypertension. DESIGN: In 43 hypertensive patients (HT) and 38 normotensive controls (NT) endothelial function of the brachial artery was assessed by measurement of flow-mediated dilatation (FMD), using high-resolution ultrasound. Peripheral flow reserve (FR) was determined via measurements of forearm blood flow at rest and during increments of reactive hyperaemia, using venous occlusion plethysmography. RESULTS: FMD was markedly impaired in HT (3.6 +/- 0.3%) as compared with NT (10.2 +/- 0.3%), whereas maximum brachial artery diameter following endothelium-independent dilatation was similar in both groups. In hypertensive patients FR was significantly reduced (HT, 3.2 versus NT, 6.0) during reactive hyperaemia after 5 min of ischaemia. FR was associated with FMD (r = 0.68, P < 0.01). Multiple stepwise regression analysis identified FR as a strong independent variable determining the extent of FMD (r2 = 0.46, P < 0.01). In HT the dose-response curve of FMD upon stepwise increases of FR was shifted significantly to the right. Normalization of FR improved FMD in HT by more than 60%. CONCLUSIONS: In essential hypertension a reduced FR contributes to the endothelial dysfunction of upstream conduit arteries. These findings may have therapeutic and prognostic implications in patients with arterial hypertension.

Coronary flow reserve measurements in hypertension.

Taken together, the diagnostic algorithm is leaded by a simple ECG stress test. In case of ST-segment depression the preferred image test should be stress ECG to bring patients at high risk for significant epicardial coronary artery stenosis to coronary angiography (and revascularization). In case of the lack of wall motion abnormalities (during stress-echo test) or absence of epicardial stenosis one may further assess coronary flow reserve with noninvasive Doppler harmonic echocardiography. For ultimate quantitative assessment invasive procedures, such as argon dilution or intracoronary Doppler techniques, represent the appropriate approach. Treatment of microvascular disease may be followed-up by these new noninvasive diagnostic approaches in future and also, at present, by monitoring ST-segment depression.

[Regression of left ventricular hypertrophy in hypertensive heart disease]. / Hypertrophieregression als Therapieprinzip des Hochdruckherzens.

PATHOPHYSIOLOGY AND THERAPY: Left ventricular hypertrophy represents an important factor determining the prognosis of hypertensive patients. Hypertrophy as identified by electrocardiography (Table 1) or echocardiography (Table 2) characterizes patients with a significantly increased risk of mortality and arrhythmia. From the pathophysiological point of view this is based on hypertrophy of the media in resistance vessels, on interstitial fibrosis, on a reduced coronary flow reserve and on the occurrence of ischemia (Figure 1). The diastolic and (later) systolic function of the heart are disturbed (Figures 2 to 4). Antihypertensive therapy with beta blockers and diuretics leads to a reduction of left ventricular mass by 5-8%, with ACE-inhibitors and AT-blockers by 13% (Figure 5). Particularly ACE-inhibitors can effectively reverse of the above mentioned pathological processes. Regression of hypertrophy goes along with an improved prognosis and a reduction of atrial and ventricular arrhythmias (Figure 6). A symptomatic treatment of arrhythmias should always be accompanied by medical therapy aimed at regression of hypertrophy. Optimal therapy results in normalizes of blood pressure, leads to a regression of hypertrophy and induces cardiac reparation, which in turn improve left ventricular function, reduces microvascular ischemia stress and arrhythmias. These therapeutic desiderates are also pertinent for hypertensive heart disease in the prehypertrophic state, as in juvenile hypertension.

Enlarged effects of adenosine in a septic patient with multiple myeloma and atrial flutter.

We report the history of a 60-year-old patient with a multiple myeloma and Staphylococcus aureus associated sepsis to whom adenosine in a dose of 6 mg was administered, when a regular, narrow QRS complex tachycardia at a heart rate of 120 beats/minute started. Adenosine led to a complete AV-block and revealed atrial flutter. Atrial flutter waves persisted for about 15 seconds and were followed by atrial and ventricular asystole for about 20 seconds. Repeated nonsustained polymorphic ventricular tachycardias followed and after about 90 seconds sinus rhythm was restored.

Long-term follow-up of sudden cardiac arrest survivors and electrophysiologically guided antiarrhythmic therapy.

Sudden cardiac arrest survivors have a high risk of suffering from recurrent arrhythmic events. Recent studies have shown that these patients have a significantly decreased mortality rate, if they are supplied with an implantable cardioverter/defibrillator (ICD). The aim of this study was to evaluate the long-term prognosis of patients with electrophysiologically guided antiarrhythmic drug therapy in comparison to patients with ICD. 204 consecutive survivors of sudden cardiac arrest were enrolled in this study. All patients were examined with an initial electrophysiologic study (EPS) with programmed ventricular stimulation. Patients were treated with antiarrhythmic drugs (if the inducible tachycardia was suppressed) or with the implantation of an ICD. The maximal follow-up period was 120 months, the mean period was 53.3 +/- 31.4 months (ICD) versus 60.3 +/- 35.5 months (EPS, nonsignificant). Patients with ICD showed an overall mortality rate of 14.6%, whereas EPS-guided patients had a mortality rate of 43.2% (p < 0.001). The cardiac and arrhythmogenic mortality rates were significantly lower in the ICD group (12 vs. 43%, p < 0.01, and 1 vs. 16%, p < 0.001, respectively). A reduction of the mortality risk was observed in the ICD group by up to 61% (all-cause mortality), 52% (cardiac mortality) and 97.2% (arrhythmogenic mortality). In arrhythmic event survivors with ICD, arrhythmic and overall mortality rates are significantly lower compared to patients with an EPS-guided drug therapy. In the secondary prevention of sudden cardiac death, ICD should be the first choice of antiarrhythmic therapy.

Parameters of left ventricular diastolic function 48 hours after coronary angioplasty and stent implantation.

INTRODUCTION: It has been reported that stent implantation results in an earlier and more pronounced improvement of coronary flow reserve in comparison to conventional balloon angioplasty. Whether this phenomenon translates into hemodynamic changes of left ventricular systolic and diastolic function has not been investigated. This study was designed to determine whether stenting leads to greater changes in measures of diastolic dysfunction than plain angioplasty alone. METHODS: Parameters of diastolic function were ascertained by Doppler echocardiography in 194 patients with single-vessel disease before and 48 hours after elective coronary angioplasty. A total of 116 patients were initially successfully treated with coronary angioplasty. In 78 patients, stents were used to improve an inadequate result after coronary angioplasty. The parameters of left ventricular diastolic function were evaluated before and 48 hours after coronary intervention by Doppler echocardiography. Ejection fraction was determined and used to characterize systolic left ventricular function. RESULTS: Both patient groups (116 patients with coronary angioplasty, 78 patients with combined coronary angioplasty and stent implantation) showed no relevant differences concerning sex, age, atherosclerotic risk factors, exercise capacity and results of exercise electrocardiography. All patients who underwent stent implantation showed an early improvement of left ventricular diastolic function 48 hours after intervention. Surprisingly, there was no significant short-term improvement (48 hours) of diastolic function in patients with initially successful angioplasty. CONCLUSION: Stent implantation results in improved left ventricular diastolic function in comparison to conventional balloon angioplasty. This has to be attributed to a more immediate and increased antiischemic effectiveness due to the scaffolding properties of stents.