Christiana Mira Schannwell

Left Ventricular Diastolic Dysfunction as an Early Manifestation of Diabetic Cardiomyopathy

Aims/Hypothesis: Early determination of myocardial manifestations of diabetes mellitus is of major importance, since myocardial involvement considerably influences the prognosis of diabetic patients. The aim of this study was to investigate whether young patients with insulin-dependent diabetes mellitus and normal systolic left ventricular (LV) function already show a diastolic LV dysfunction and an increased risk of arrhythmias. Methods: Echocardiography was performed in 87 patients suffering from type I diabetes mellitus, without known cardiac disease and in 87 controls. Patients with a known manifest cardiac disease or a long-term diabetic syndrome were excluded. Morphological parameters were determined using M-mode echocardiography. Doppler echocardiography was used to evaluate parameters of LV diastolic function. The risk of arrhythmia was assessed by means of electrocardiography, heart rate variability, and late potential analysis. Results: The left atrial and ventricular dimensions and systolic functional parameters of all patients were normal. A diastolic dysfunction with a reduction in early diastolic filling, an increase in atrial filling, an extension of isovolumetric relaxation and deceleration time was documented in diabetic patients, as well as an increased number of supraventricular and ventricular premature beats. Conclusion: Even young patients with diabetes mellitus suffer from a diastolic dysfunction while systolic ventricular function is normal. Therefore, echocardiography with measurements of diastolic functional parameters appears to be a sensitive method for evaluating the manifestation and course of early diabetic cardiomyopathy.

The BALANCE Study: Clinical Benefit and Long-Term Outcome After Intracoronary Autologous Bone Marrow Cell Transplantation in Patients With Acute Myocardial Infarction

OBJECTIVES The aim of this study was to investigate the quantitative amount of improvement of ventricular hemodynamic status, geometry, and contractility as well as the long-term clinical outcome of cell-treated patients after acute myocardial infarction (AMI). BACKGROUND Animal experiments as well as clinical studies have demonstrated that autologous bone marrow cell (BMC) transplantation might improve ventricular function and prevent remodeling. METHODS Sixty-two patients underwent intracoronary autologous BMC transplantation 7 +/- 2 days after AMI. Cells were infused directly into the infarct-related artery. The control group consisted of 62 patients with comparable left ventricular (LV) ejection fraction (EF) and diagnosis. All patients had several examinations (e.g., coronary angiography, right heart catheterization, biplane left ventriculography, electrocardiogram [ECG] at rest and exercise, echocardiography, late potential [LP], heart rate variability [HRV], and 24-h Holter ECG). The therapeutic follow-up was performed 3, 12, and 60 months after BMC therapy. RESULTS Three months after BMC therapy there was significant improvement of EF and stroke volume index. The infarct size was significantly reduced by 8%. Contraction velocities (lengths/second, volumes/second) increased significantly and the slope of the ventricular function curve (systolic pressure/end-systolic volume) became steeper. There was significant improvement of contractility in the infarct zone, as evidenced by a 31% increase of LV velocity of shortening (VCF), preferably in the border zone of the infarct zone. In contrast, the noninfarcted area showed no difference in VCF before and after BMC therapy. Furthermore, decreases of abnormal HRV, LP, and ectopic beats were documented after BMC therapy. Twelve and 60 months after BMC therapy the parameters of contractility, hemodynamic status, and geometry of the LV were stable. The exercise capacity of treated patients was significantly augmented, and the mortality was significantly reduced in comparison with the control group. CONCLUSIONS BMC therapy leads to significant and longstanding improvements of LV performance as well as quality of life and mortality of patients after AMI. After BMC therapy, no side effects were observed, showing that BMC therapy is safe.

The acute and long-term effects of intracoronary Stem cell Transplantation in 191 patients with chronic heARt failure: the STAR-heart study

Despite accumulated evidence that intracoronary bone marrow cell (BMC) therapy may be beneficial in acute myocardial infarction, there are only limited data available on the effectiveness of BMCs in chronic heart failure. The aim of this study was to quantitatively investigate ventricular haemodynamics, geometry, and contractility as well as the long‐term clinical outcome of BMC treated patients with reduced left ventricular ejection fraction (LVEF) due to chronic ischaemic cardiomyopathy.

Clinical ResearchClinical TrialThe BALANCE Study: Clinical Benefit and Long-Term Outcome After Intracoronary Autologous Bone Marrow Cell Transplantation in Patients With Acute Myocardial Infarction

OBJECTIVES The aim of this study was to investigate the quantitative amount of improvement of ventricular hemodynamic status, geometry, and contractility as well as the long-term clinical outcome of cell-treated patients after acute myocardial infarction (AMI). BACKGROUND Animal experiments as well as clinical studies have demonstrated that autologous bone marrow cell (BMC) transplantation might improve ventricular function and prevent remodeling. METHODS Sixty-two patients underwent intracoronary autologous BMC transplantation 7 +/- 2 days after AMI. Cells were infused directly into the infarct-related artery. The control group consisted of 62 patients with comparable left ventricular (LV) ejection fraction (EF) and diagnosis. All patients had several examinations (e.g., coronary angiography, right heart catheterization, biplane left ventriculography, electrocardiogram [ECG] at rest and exercise, echocardiography, late potential [LP], heart rate variability [HRV], and 24-h Holter ECG). The therapeutic follow-up was performed 3, 12, and 60 months after BMC therapy. RESULTS Three months after BMC therapy there was significant improvement of EF and stroke volume index. The infarct size was significantly reduced by 8%. Contraction velocities (lengths/second, volumes/second) increased significantly and the slope of the ventricular function curve (systolic pressure/end-systolic volume) became steeper. There was significant improvement of contractility in the infarct zone, as evidenced by a 31% increase of LV velocity of shortening (VCF), preferably in the border zone of the infarct zone. In contrast, the noninfarcted area showed no difference in VCF before and after BMC therapy. Furthermore, decreases of abnormal HRV, LP, and ectopic beats were documented after BMC therapy. Twelve and 60 months after BMC therapy the parameters of contractility, hemodynamic status, and geometry of the LV were stable. The exercise capacity of treated patients was significantly augmented, and the mortality was significantly reduced in comparison with the control group. CONCLUSIONS BMC therapy leads to significant and longstanding improvements of LV performance as well as quality of life and mortality of patients after AMI. After BMC therapy, no side effects were observed, showing that BMC therapy is safe.

Left Ventricular Hypertrophy and Diastolic Dysfunction in Healthy Pregnant Women

Objective: The purpose of this study was to examine which hemodynamic parameters change under the natural volume overload of pregnancy. Study Design: 46 healthy pregnant women were echocardiographically examined during the course of pregnancy. To evaluate left ventricular diastolic function, mitral inflow and pulmonary venous flow profiles were used. Fractional shortening and left ventricular muscle mass were calculated. Results: In the course of pregnancy the left ventricular muscle mass index increased (from 66 ± 6 to 96 ± 9 g/m2), fractional shortening decreased (from 38 ± 4 to 32 ± 6%) and a disturbed diastolic relaxation pattern was documented. Eight weeks after delivery, all left ventricular systolic and diastolic functional parameters returned to normal values. Conclusion: The natural volume overload in pregnancy leads to a reversible ‘physiological’ left ventricular hypertrophy, a short-term decrease in systolic function and a significant change in left ventricular diastolic function.

Left ventricular diastolic function in physiologic and pathologic hypertrophy

BACKGROUND Patients with hypertensive heart disease and left ventricular hypertrophy demonstrate an impaired left ventricular diastolic filling pattern. The aim of this study was to find out whether physiologic left ventricular hypertrophy induced by endurance training causes disturbances in left ventricular systolic and diastolic filling. METHODS We examined 49 athletes with left ventricular (LV) hypertrophy due to endurance training, 49 patients with LV hypertrophy due to arterial hypertension, and 26 untrained healthy control subjects by conventional echocardiography. Parameters of LV diastolic filling using pulse wave and color flow Doppler were also assessed. RESULTS All three study groups showed normal fractional shortening and mid-wall fractional shortening. Conventional echocardiography revealed a higher LV muscle mass index in the two study groups compared with the controls (athletes, 99 +/- 10 g; hypertensive patients, 95 +/- 11 g: controls: 52 +/- 7 g; P < .01 for athletes and hypertensive patients). In patients with arterial hypertension, a diastolic dysfunction consisting of a delayed relaxation pattern with a decrease in maximal early velocity of diastolic filling (0.44 +/- 0.1 m/sec) and a compensatory increase of the maximal late velocity of diastolic filling (0.53 +/- 0.1 m/sec) was demonstrated. In athletes with physiologic LV hypertrophy, a normal LV diastolic filling pattern was documented. CONCLUSIONS Doppler echocardiographic parameters of LV diastolic function can be of diagnostic importance for discrimination between pathologic and physiologic LV hypertrophy.

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 H2O) 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.

Hypertensive mikrovaskuläre Erkrankung

ZusammenfassungDie arterielle Hypertonie stellt einen relevanten kardiovaskulären Risikofaktor dar und führt sowohl zu vaskulären als auch zu myokardialen Manifestationen am Herzen. Besondere Bedeutung kommt der hypertensiv bedingten koronaren Mikroangiopathie zu. Das klinische Bild des Patienten mit hypertensiv bedingter koronarer Mikroangiopathie wird durch die Koronarinsuffizienz mit typischer Angina pectoris, aber auch Herzinsuffizienz (systolische und diastolische Dysfunktion) und Herzrhythmusstörungen bestimmt.Die Diagnose der hypertensiven mikrovaskulären Erkrankung kann durch nichtinvasive und invasive Verfahren vermutet werden; eine Sicherung der Diagnose ist nur durch Bestimmung der koronaren Flussreserve möglich.Primäres Therapieziel ist neben der effektiven Blutdrucknormalisierung die Rückführung der hypertensiv bedingten kardialen Veränderungen durch die Einleitung spezifischer Therapiemaßnahmen.AbstractArterial hypertension is a major cardiovascular risk factor and leads to vascular as well as to myocardial manifestations. Particularly hypertensive microvascular disease is of great importance. Major clinical manifestations of hypertensive heart disease are symptoms of coronary insufficiency with typical angina pectoris, but also heart failure (systolic or diastolic dysfunction) and arrhythmia.Different non-invasive and invasive procedures are available for screening. For ultimate quantitative assessment of the coronary reserve, invasive procedures are still required. Beside lowering blood pressure primary therapeutic target is to reverse cardiac manifestations of arterial hypertension using specific therapeutic algorithms.

Effect of implantable cardioverter/defibrillator lead placement in the right ventricle on defibrillation energy requirements. A combined experimental and clinical study

OBJECTIVES The effect of implantable cardioverter/defibrillator (ICD) lead placement in the right ventricle (RV) on defibrillation efficacy has not been thoroughly investigated. Therefore, the goal of this combined experimental and clinical study was to evaluate the effect of a septal and a non-septal position of the right ventricular endocardial spring lead on defibrillation energy. METHODS In 12 isoflurane-anaesthetized swine and subsequently in 8 patients who underwent ICD implantation, two different positions of the distal spring lead in the RV were investigated in randomized order: non-septal position (free wall of the RV) and septal position (interventricular septum). For each position, separate 50% probability determinations of energy (E50), peak voltage (V50) and peak current (A50) were calculated using the three reversal up/down defibrillation procedure. The E50, V50, A50 and impedance (I) were averaged and compared using the two-sided t-test for paired samples. RESULTS Both the experimental study and the clinical study demonstrated that placing the distal defibrillation lead near to the septum rather than near to the ventricular free wall resulted both in the swine and in the patients in significantly lower E50-31.6%/ - 37.1%, V50-16.1%/-20.9% and A50 -10.0%/ - 24.2%, respectively. Defibrillation impedances were significantly reduced only in the experimental study. CONCLUSIONS Defibrillation efficacy depends on the position of the distal spring electrode in the RV. A septal position significantly reduces the energy requirements compared to a non-septal position. The decrease in energy requirements might be explained by an increase in current flow through the septum and the posterolateral wall of the left ventricle. reserved

Hypertrophieregression als Therapieprinzip des Hochdruckherzens

Pathophysiologie und Therapie:Die linksventrikuläre Hypertrophie stellt einen wesentlichen, die Prognose des Hypertonikers bestimmenden Faktor dar. Eine elektrokardiographisch oder echokardiographisch determinierte Hypertrophie charakterisiert einen Patienten mit einem signifikant erhöhten Mortalitäts- und Arrhythmierisiko. Strukturell beruht die Hypertrophie der Ventrikelwände auf einer Hypertrophie der Kardiomyozyten, einer Mediahypertrophie der Widerstandsgefäße und einer interstitiellen Fibrose; dazu kommt es zur Einschränkung der koronaren Regulationsbreite, dem Auftreten von Ischämien und einer diastolischen Dysfunktion. Herzrhythmusstörungen sind das klinische Korrelat, das zur wiederholten kurzzeitigen Symptomatik oder zum plötzlichen fatalen Ereignis führen kann. Die antihypertensive Therapie führt zu einer Reduktion der Muskelmasse bei Therapie mit Betablockern und Diuretika von 5–8% und bei Therapie mit ACE-Hemmern und AT-Blockern bis zu 13%. Gerade unter ACEHemmung sind die oben beschriebenen pathologischen Umbauprozesse umkehrbar. Die optimale kausale Therapie bewirkt eine Blutdrucknormalisierung, eine Hypertrophieregression und eine Kardioreparation mit verbesserter linksventrikulärer Funktion, Abnahme einer mikrovaskulären Ischämiebelastung und Verminderung der Arrhythmien. Diese therapeutischen Ziele sind i. S. einer Prävention für das Hochdruckherz auch im prähypertrophierten Zustand sowie bei juveniler Hypertonie von Bedeutung.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.