Marcus Hennersdorf

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.

Arterial hypertension and cardiac arrhythmias.

Purpose and data identification One of the main clinical problems of patients with arterial hypertension is the presence of arrhythmias, especially if left ventricular hypertrophy exists. Recent results from our group and all data available via Med-Line-search have been analysed. The analysis was focused on atrial and ventricular arrhythmias and arrhythmic risk prediction, using non-invasive markers. Results of analysis and conclusion Arterial hypertension is a major cause of non-rheumatic atrial fibrillation and other supraventricular arrhythmias. The prevalence of ventricular arrhythmias is increased in hypertensive patients without left ventricular hypertrophy, compared to normotensives. If left ventricular hypertrophy is present, the risk for ventricular tachycardias is quadrupled. The presence of left ventricular hypertrophy is associated with an increase in all-cause mortality by a factor of seven in men and nine in women. In particular, patients with hypertrophy, increased rate of ventricular extrasystoles up to non-sustained ventricular tachycardia and ST-depression in long-term ECG are threatened by sudden cardiac death. At present, it is not possible to safely identify patients with increased risk. Regression of hypertrophy exists along with a decreased rate of ventricular extrasystoles. We hypothesize that by the regression of hypertrophy, the prevalence of sustained ventricular tachycardia decreases and therefore the prognosis of those patients can be improved, although controlled studies are not yet available.

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

RationaleThere 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.ObjectivesTo determine whether sleep apnea is associated with increased late lumen loss and restenosis after percutaneous coronary intervention.Methods78 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 resultsAngiographic 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).ConclusionIn 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.

T Wave Alternans as a Risk Predictor in Patients with Cardiomyopathy and Mild-to-Moderate Heart Failure

The analysis oft wave alternans (TWA) was introduced to identify patients with an increased risk of ventricular tachyarrhythmias. The inducibility of ventricular tach‐yarrhythmias and the spontaneous arrhythmic events are correlated with a positive TWA in patients with a reduced left ventricular ejection fraction and survived myocardial infarction. In contrast, this study is the first to investigate the correlation of a survived sudden cardiac death and TWA in patients without coronary heart disease and only slightly decreased left ventricular function. Sixty patients were included in the study. The TWA analysis was performed using the Cambridge Heart system (CH2000). Patients were sitting on a bicycle ergometer and exercised with a gradual increase of workload to maintain a heart rate of at least 105 beats/min. The exercise test was stopped after recording 254 consecutive low noise level heart beats. The electrocardiographic signals were digitally processed using a spectral analysis method. The magnitude of TWA was measured at a frequency of 0.5 cycles/beat. A TWA was defined as positive if the ratio between TWA and noise level was > 3.0 and the amplitude of the TWA was > 1.8 μV. Twelve (20%) of the included 60 patients showed a positive TWA. The sensitivity concerning a previous arrhythmic event amounted to 65%, the specificity up to 98%, respectively. The alternans ratio was significantly higher in patients with a previous event (30.3 ± 53.2 vs 2.9 ± 5.9, P < 0.001) and cumulative alternans voltage (4.67 ± 3.55 vs 1.75 ± 1.88 μV, P < 0.001). In 19 patients, invasively investigated by an electro‐physiological study, a significant correlation between inducibility of tachyarrhythmias and a positive TWA result was found (Spearman R = 0.51, P = 0.01). In conclusion, the TWA analysis seems to identify patients with nonischemic Cardiomyopathy who are at an increased risk of ventricular tachyarrhythmias.

Ivabradine as an Alternative Therapeutic Trial in the Therapy of Inappropriate Sinus Tachycardia

Inappropriate sinus tachycardia is a disease which is relatively rarely found and sometimes difficult to treat. Up to now it has been mostly treated with a β-blocker or verapamil. If this did not work sinus node modulation was considered. Since the relatively new selective IF-stream blocker ivabradine has been approved for the therapy of chronic stable angina pectoris, a new therapeutic option is available. As ivabradine is well tolerated and only few side effects are known, it may become a new therapeutic step between medication and the invasive sinus node modulation. We report the case of a young female patient with inappropriate sinus tachycardia where a sustained therapeutic success was achieved with ivabradine medication as an alternative therapeutic trial after various ineffective medications.

T Wave Alternans and Ventricular Arrhythmias in Arterial Hypertension

Patients with a positive microvolt-level T wave alternans (TWA) are characterized by an increased risk of ventricular tachyarrhythmias. Arterial hypertension leads to an increase of sudden cardiac death risk, particularly if left ventricular hypertrophy is present. The aim of this study was to investigate the value of TWA in patients with arterial hypertension. Fifty-one consecutive patients were included in the study. TWA analysis was performed with patients sitting on a bicycle ergometer and exercising with a gradual increase of workload to maintain a heart rate of at least 105/min. After recording 254 consecutive low-noise-level heartbeats, the exercise test was stopped. The ECG signals were digitally processed by a spectral analysis method. The magnitude of TWA was measured at a frequency of 0.5 cycle per beat. A TWA was defined as positive if the ratio between TWA and noise level was >3.0 and the amplitude of the TWA was >1.8 &mgr;V. Eight of the 51 patients (16%) showed a positive TWA. If left ventricular hypertrophy was present, the prevalence of TWA was higher (33.3% versus 8.3%;P <0.05). Sensitivity concerning a previous arrhythmic event was 73%, and specificity was 100%. The alternans ratio was significantly higher in patients with a previous event (39.3±62.3 versus 2.4±4.6;P <0.001), as was the cumulative alternans voltage (4.7±4.1 versus 1.6±1.9 &mgr;V;P <0.001). In 16 patients invasively investigated by an electrophysiological study, a significant correlation between inducibility of tachyarrhythmias and a positive TWA result was found (Spearman R =0.36, P =0.01). We conclude that the arrhythmic risk of patients with arterial hypertension is markedly increased if microvolt-level TWA is present. The prevalence of TWA is higher in patients with left ventricular hypertrophy.

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/m2), and group B those (45.2%) who showed a progression of LVMMI (122.2±3.2 vs. 143.2±3.2 g/m2). 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.

Myocardial delayed contrast enhancement in patients with arterial hypertension: initial results of cardiac MRI

Purpose: In arterial hypertension left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations of the coronary microcirculation. MRI enables the detection of myocardial fibrosis, infarction and scar tissue by delayed enhancement (DE) after contrast media application. Aim of this study was to investigate patients with arterial hypertension but without known coronary disease or previous myocardial infarction to detect areas of DE. Methods and material: Twenty patients with arterial hypertension with clinical symptoms of myocardial ischemia, but without history of myocardial infarction and normal coronary arteries during coronary angiography were investigated on a 1.0 T superconducting magnet (Gyroscan T10-NT, Intera Release 8.0, Philips). Fast gradient-echo cine sequences and T2-weighted STIR-sequences were acquired. Fifteen minutes after injection of Gadobenate dimeglumine inversion recovery gradient-echo sequences were performed for detection of myocardial DE. Presence or absence of DE on MRI was correlated with clinical data and the results of echocardiography and electrocardiography, respectively. Results: Nine of 20 patients showed DE in the interventricular septum and the anteroseptal left ventricular wall. In 6 patients, DE was localized intramurally and in 3 patients subendocardially. There was a significant correlation between myocardial DE and ST-segment depressions during exercise and between DE and left-ventricular enddiastolic pressure. Patients with intermittent atrial fibrillation showed a myocardial DE more often than patients without atrial fibrillation. Conclusion: In our series, 45% of patients with arterial hypertension showed DE on cardiac MRI. In this clinical setting, delayed enhancement may be due to coronary microangiopathy. The more intramurally localization of DE, however, rather indicates myocardial interstitial fibrosis.

Chemoreflexsensitivity in chronic heart failure patients

Patients with heart failure are characterised by a disturbed sympathovagal balance, as could be shown by analyses of heart rate variability and baroreflexsensitivity. Furthermore, the modulation of ventilation is disturbed in those patients with an increased ventilation volume following the inhalation of hypoxic gas. This study should evaluate, whether heart failure patients have a decreased hyperoxic chemoreflexsensitivity associated with an increased rate of ventricular arrhythmias.

Chemoreflexsensitivity in Patients with Survived Sudden Cardiac Arrest and Prior Myocardial Infarction

For evaluation of patients with an increased risk of sudden cardiac death, the analyses of ventricular late potentials, heart rate variability, and baroreflexsensitivity are helpful. But so far, the prediction of a malignant arrhythmic event is not possible with sufficient accuracy, For a better risk stratification other methods are necessary. In this study the importance of the ChRS for the identification of patients at risk for ventricular tachyarrhythmic events should be investigated. Of 41 patients included in the study, 26 were survivors of sudden cardiac arrest. Fifteen patients were not resuscitated, of whom 6 patients had documented monomorphic ventricular tachycardia and 9 had no ventricular tachyarrhythmias in their prior history. All patients had a history of an old myocardial infarction (> 1 year ago). For determination of the ChRS the ratio between the difference of the RR intervals in the ECG and the venous pO2 before and after a 5‐minute oxygen inhalation via a nose mask was measured (ms/mmHg). The 26 patients with survived sudden cardiac death showed a significantly decreased ChRS compared to those patients without a tachyarrhythmic event (1.74 ± 1.02 vs 6.97 ± 7.14 ms/mmHg, P < 0.0001). The sensitivity concerning a survived sudden cardiac death amounted to 88% for a ChRS below 3.0 ms/mmHg. During a 12‐month follow‐up period, the ChRS was significantly different between patients with and without an arrhythmic event (1.64 ± 1.06 vs 4.82 ± 5.83 ms/mmHg, P < 0.01). As a further method for evaluation of patients with increased risk of sudden cardiac death after myocardial infarction the analysis of ChRS seems to be suitable and predicts arrhythmias possibly more sensitive than other tests of neurovegetative imbalance. The predictive importance has to be examined by prospective investigations in larger patient populations.