Stefan Perings

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.

Incidence and clinical outcome of iatrogenic femoral arteriovenous fistulas: Implications for risk stratification and treatment

OBJECTIVES We sought to determine the incidence of arteriovenous fistulas (AVF), identify risk factors for AVF, and follow up the clinical outcome of femoral AVF. BACKGROUND Arteriovenous fistulas are a potential harmful complication of cardiac catheterization. Incidence and clinical outcome of iatrogenic AVF are unknown so far, although important for risk stratification and treatment. METHODS A total of 10,271 consecutive patients undergoing cardiac catheterization were followed up prospectively over a period of three years. Diagnosis of AVF was performed by duplex sonography. RESULTS The incidence of AVF was 0.86% (n = 88). The following significant and independent risk factors for AVF were identified: high heparin dosage (odds ratio [OR]) = 2.88), coumadin therapy (OR = 2.34), puncture of the left groin (OR = 2.21), arterial hypertension (OR = 1.86), and female gender (OR = 1.84). Within 12 months 38% of all AVF closed spontaneously. No signs of cardiac volume overload or limb damage were observed in patients with persisting AVF. None of the risk factors for AVF influenced the incidence or the rate of AVF closure. Only intensified anticoagulation showed a tendency to extend AVF persistence. CONCLUSIONS Almost 1% of patients undergoing cardiac catheterization acquire femoral AVF, for which patient- and procedure-related risk factors could be identified. One-third of iatrogenic AVF close spontaneously within one year. Cardiac volume overload and limb damage are highly unlikely with AVF persistence. Thus, a conservative management for at least one year seems to be justified.

Nitric oxide induced contractile dysfunction is related to a reduction in myocardial energy generation

OBJECTIVE It has been suggested that nitric oxide (NO) is involved in the regulation of myocardial function in a variety of diseases such as dilated cardiomyopathy, myocarditis, heart transplant rejection, and septic shock. However, the underlying mechanism of NO mediated reduction of cardiac contractility has not been clearly established so far. Therefore, we studied the effects of authentic NO on left ventricular function and myocardial energy status in the isolated heart. METHODS In 43 isolated perfused guinea pig hearts quantitative and kinetic changes in coronary flow (CF), left ventricular developed pressure (LVDP), the cardiac release of adenosine, lactate, cyclic GMP, and norepinephrine were measured during infusion of authentic NO. In parallel, myocardial phosphocreatine (PCr), ATP and the free energy change of ATP-hydrolysis (delta GATP) were measured using 31P nuclear magnetic resonance spectroscopy. RESULTS At low concentrations (0.01 to 1.0 mumol/L) NO increased CF only; at higher concentrations (1 to 100 mumols/L) CF remained elevated and LVDP was significantly reduced. Onset and offset of changes in LVDP occurred always within 2 to 5 s after start and cessation of NO infusion. Contractile dysfunction was significantly correlated to a pronounced increase in adenosine formation (> 70-fold), a significant decrease in myocardial PCr (-78%), ATP (-25%) and a decrease in delta G(ATP) from -61.76 kJ/mol to -50.75 kJ/mol. This was paralleled by a significant decrease in myocardial oxygen consumption (-65%) and a tenfold increase in lactate production. Coronary vasodilation (NO: 0.001 to 1.0 mumol/L) significantly correlated with the increase in cGMP release, whereas at negative inotropic concentrations (NO: 10 to 100 mumols/L) a clear quantitative and kinetic dissociation between NO-induced changes in cGMP and LVDP was observed. Contractile dysfunction was not related to cardiac release of norepinephrine. CONCLUSIONS In the isolated heart NO can potently depress myocardial energy generation thus being an effective modulator of cardiac contractility. This effect of NO may be of pathophysiological significance in cardiac muscle disorders in vivo.

A prospective study on incidence and risk factors of arteriovenous fistulae following transfemoral cardiac catheterization

BACKGROUND A potentially harmful complication of cardiac catheterization is the arteriovenous fistula. Precise knowledge of possible factors predisposing for acquisition of iatrogenic AV-fistulae could enable cardiologists to perform a risk stratification for cardiac patients prior to catheterization. METHODS Over a period of 2 years, 10,271 consecutive patients who underwent cardiac catheterization were included in this study. Auscultation of a new femoral bruit was followed by a duplex scan to confirm the suspected diagnosis of an AVF. Every patient was investigated on the day after catheterization. RESULTS The incidence of iatrogenic AVF was 0.86%. A multivariate regression analysis revealed five significant and independent risk factors: (1) procedural heparin dosage >or=12,500 IU (Odds Ratio (OR)=2.88), (2) coumadin therapy (OR=2.34), (3) puncture of the left groin (OR=2.21), (4) arterial hypertension (OR=1.86) and (5) female gender (OR=1.84). Coronary angioplasty (instead of diagnostic procedure), size and number of sheaths, age and body mass index did not significantly affect the incidence of AVF. CONCLUSIONS The overall incidence of AV-fistulae following cardiac catheterization approximates 1%. Determination of significant risk factors will facilitate identification of patients at risk for iatrogenic arteriovenous fistulae prior to cardiac catheterization and thus help to develop strategies to reduce the incidence of AV-fistulae.

Comparison of Right Ventricular Functional Response to Exercise in Hypertrophic Versus Idiopathic Dilated Cardiomyopathy

Although the biventricular nature of the disease has been confirmed by morphologic studies, information on right ventricular (RV) function in hypertrophic cardiomyopathy (HC) is lacking. The aim of the study was to hemodynamically characterize RV performance in HC versus idiopathic dilated cardiomyopathy (IDC) during exercise. The hemodynamic data of 63 patients with HC who underwent hemodynamic exercise testing with thermodilution-derived assessment of RV ejection fraction were analyzed. The results were compared to a healthy control group (n = 20) and to patients with IDC (n = 86). The baseline RV ejection fraction was increased in the patients with HC compared to those with IDC (39 +/- 10% vs 33 +/- 12%; p = 0.002), but did not differ compared to controls (42 +/- 7% vs 39 +/- 10%; p = NS). An increase in end-diastolic volume from rest to exercise contributed to stroke volume augmentation in those with HC (121 +/- 38 vs 136 +/- 55 ml/m(2); p = 0.01) and control subjects (116 +/- 34 vs 138 +/- 31 ml/m(2); p = 0.002) but not in those with IDC (117 +/- 47 vs 120 +/- 52 ml/m(2); p = NS). At peak exercise the RV ejection fraction in those with HC was reduced compared to that in the controls (45 +/- 11% vs 59% +/- 9%; p <0.001), but it was increased compared to that in those with IDC (45 +/- 11% vs 35% +/- 11%; p <0.001). In conclusion, the extent of the pulmonary pressure increase was more pronounced in those with HC than in those with IDC, but the degree of functional impairment of the right ventricle was less severe, probably owing to its ability to recruit preload and contractile reserve with exercise.

Age-related decline of PCr/ATP-ratio in progressively hypertrophied hearts of spontaneously hypertensive rats

Abstract Although the ultimate cause for the myocardial dysfunction of hypertensive heart disease is still unclear, a crucial role of the myocardial energy metabolism has been suggested. Therefore, the aim of the present study was to investigate whether age-related myocardial dysfunction in hearts of spontaneously hypertensive rats (SHR) is associated with an impaired myocardial energy metabolism. Isolated hearts of SHR and Wistar Kyoto rats (WKY) aged about 40, 60, and 80 weeks, respectively (each n = 4–5), were perfused according to the working heart technique. Cardiac work and coronary flow were monitored online. Myocardial energy metabolism was evaluated by calculating the ratio of phosphocreatine (PCr) and adenosine triphosphate (ATP) which were measured by nuclear magnetic resonance (31P-NMR) spectroscopy. All hearts were subjected to work for 30 min at baseline conditions (low afterload), followed by another 30 min under a moderate pressure load (high afterload). Each SHR group showed a higher heart weight/body weight ratio than the age-matched WKY controls. The SHR showed a progressive age-dependent reduction of cardiac work (40 weeks = 5.1 ± 0.3, 60 weeks = 4.0 ± 0.3, 80 weeks = 3.8 ± 0.2 (mW/g) at baseline conditions) and PCr/ATP-ratio (40 weeks = 1.82 ± 0.06, 60 weeks = 1.69 ± 0.05, 80 weeks = 1.59 ± 0.09 (PCr/ATP) at baseline conditions). Similar results were found for hearts of SHR at high afterload. In WKY no significant decline in cardiac work or PCr/ATP-ratio was found under either low or under high afterload. The cardiac work capacity of hearts of SHR progressively decreases with increasing age and left ventricular hypertrophy. This myocardial dysfunction is closely associated with an impaired PCr/ATP-ratio, suggesting a decreased energy reserve.

Disproportionate shortening of left ventricular diastolic duration in patients with dilated cardiomyopathy

ZusammenfassungHintergrund und Ziel:Das Verhältnis von Systolen- und Diastolendauer wird als eine wichtige Determinante der Herzfunktion angesehen. Bei Kindern mit dilatativer Kardiomyopathie (DCM) konnte eine abnorme Verkürzung der Diastolendauer beobachtet werden. In der vorliegenden Studie wurde untersucht, ob sich dieser Befund bei Erwachsenen reproduzieren lässt und welches Verhalten der diastolische Anteil des Herzzyklus unter stufenweiser ergometrischer Belastung zeigt.Patienten und Methodik:Die Untersuchung schloss konsekutiv 61 Patienten mit DCM im NYHA-Stadium (New York Heart Association) II–III ein. Bei diesen wurde unter ergometrischer Belastung eine Radionuklidventrikulographie mit hoher zeitlicher Auflösung durchgeführt. Aus der Zeit-Aktivitäts-Kurve wurde neben der linksventrikulären Ejektionsfraktion die Dauer von linksventrikulärer Systole und Diastole abgeleitet. Als Vergleichskollektiv dienten 26 Patienten, bei denen eine normale linksventrikuläre Pumpfunktion mittels Radionuklidangiographie vor geplanter Chemotherapie sichergestellt wurde.Ergebnisse:Der Vergleich der relativen Systolendauer ergab bei Patienten mit DCM bereits in Ruhe eine signifikante Verlängerung gegenüber Herzgesunden (23,9 vs. 21,5 s/min; p = 0,006). Dieser Befund blieb unter maximaler Belastung signifikant (29,2 vs. 26,7 s/min; p = 0,01), obwohl der Herzfrequenzanstieg in der Patientengruppe vermindert war (118 vs. 127/min; p = 0,04). Um den Einfluss der Herzfrequenz auf die Diastolendauer der DCM-Patienten zu eliminieren, wurden die beobachteten Werte mit den rechnerisch aus der Regressionsgleichung Herzgesunder ermittelten Werten verglichen. Dieses Vorgehen bestätigte eine signifikante Verkürzung der Diastolendauer auf maximaler Belastungsstufe und eine Zunahme des Verlusts an diastolischer Zeit pro Herzschlag gegenüber dem Ruhewert.Schlussfolgerung:Patienten mit fortgeschrittener DCM weisen eine abnorme Verkürzung der linksventrikulären Diastolendauer auf. Diese ist unter körperlicher Belastung besonders ausgeprägt und kann die kardiale Effizienz durch Restriktion von ventrikulärer Füllung und Perfusion beeinträchtigen.AbstractBackground and Purpose:Cardiac performance can be characterized in terms of the relative duration of systole and diastole. In pediatric patients with dilated cardiomyopathy (DCM), a disproportionate shortening of left ventricular diastole was observed. The present study was intended to reproduce these findings in an adult patient group and to evaluate exercise-related changes of both time intervals.Patients and Methods:Exercise radionuclide angiography was used in 61 patients with DCM NYHA (New York Heart Association) stage II–III. The phases of the cardiac cycle were derived from a radionuclide time-activity curve with high temporal resolution. The control group consisted of 26 patients referred for ventricular function assessment with radionuclide angiography before cardiotoxic cancer treatment.Results:When the duration of systole was expressed as the product of systolic time and heart rate, DCM patients exhibited a significant increase in left ventricular systolic time at rest (23.9 vs. 21.5 s/min; p = 0.006) and during peak exercise (29.2 vs. 26.7 s/min; p = 0.01). The prolongation of left ventricular systole at peak exercise was evident, although the peak heart rate was significantly lower in the patient group than in the control group (118 vs. 127/min; p = 0.04). In DCM patients the diastolic time loss per beat was further quantified using a regression equation obtained from the healthy control group. A significant shortening of left ventricular diastolic time was confirmed during peak exercise. Furthermore, a progressive loss in diastolic time per beat from rest to peak exercise was noted.Conclusion:Cardiac cycle abnormalities of patients with DCM are characterized by a prolongation of left ventricular systole and an abnormal shortening of left ventricular diastole. The systolic-diastolic mismatch is accentuated during exercise and has the potential to impair the cardiac reserve in these patients by restricting ventricular filling and perfusion.

Comparative Evaluation of Thermodilution and Gated Blood Pool Method for Determination of Right Ventricular Ejection Fraction at Rest and during Exercise

Background: Since the development of a Swan-Ganz thermodilution ejection fraction catheter several studies have been published which compare this technique for obtaining right ventricular ejection fraction (RVEFTD) with alternative methods. However, the reliability of RVEFTD measurements under exercise conditions remains undetermined. Therefore, the aim of the present study was a comparative evaluation of RVEFTD with the established gated blood pool method (RVEFGBP) under exercise conditions. Methods and Results: Twenty-two patients with different cardiac diseases underwent right heart catheterization, including RVEFTD and simultaneous RVEFGBP determination at rest and during supine bicycle exercise. Linear regression analysis showed a significant correlation between RVEFTD and RVEFGBP at rest (r = 0.73, p ≤ 0.0005) and during exercise (r = 0.74, p ≤ 0.0005). A Wilcoxon analysis showed a high probability of agreement of RVEFTD and RVEFGBP at rest and exercise (level of significance for error of the 0 hypothesis of 95.9/73.3%). Conclusion: The thermodilution ejection fraction catheter provides a useful device for reliable, repetitive and safe RVEF measurements, not only at rest but also under exercise conditions. This seems to be clinically important, because by it means RVEF, as a sensitive parameter of primary or secondary right ventricular dysfunction, can be determined in the course of standard right heart catheterization.

Improvement of Left Ventricular Function under Cardiac Resynchronization Therapy Goes along with a Reduced Incidence of Ventricular Arrhythmia

Objectives The beneficial effects of cardiac resynchronization therapy (CRT) are thought to result from favorable left ventricular (LV) reverse remodeling, however CRT is only successful in about 70% of patients. Whether response to CRT is associated with a decrease in ventricular arrhythmias (VA) is still discussed controversially. Therefore, we investigated the incidence of VA in CRT responders in comparison with non-responders. Methods In this nonrandomized, two-center, observational study patients with moderate-to-severe heart failure, LV ejection fraction (LVEF) ≤35%, and QRS duration >120 ms undergoing CRT were included. After 6 months patients were classified as CRT responders or non-responders. Incidence of VA was compared between both groups by Kaplan-Meier analysis and Cox regression analysis. ROC analysis was performed to determine the aptitude of LVEF cut-off values to predict VA. Results In total 126 consecutive patients (64±11years; 67%male) were included, 74 were classified as responders and 52 as non-responders. While the mean LVEF at baseline was comparable in both groups (25±7% vs. 24±8%; P = 0.4583) only the responder group showed an improvement of LVEF (36±6% vs. 24±7; p<0.0001) under CRT. In total in 56 patients VA were observed during a mean follow-up of 28±14 months, with CRT responders experiencing fewer VA than non-responders (35% vs. 58%, p<0.0061). Secondary preventive CRT implantation was associated with a higher likelihood of VA. As determined by ROC analysis an increase of LVEF by >7% was found to be a predictor of a significantly lower incidence of VA (AUC = 0.606). Conclusions Improvement of left ventricular function under cardiac resynchronization therapy goes along with a reduced incidence of ventricular arrhythmia.

Abnorme Verkürzung der linksventrikulären Diastolendauer unter körperlicher Belastung bei Patienten mit dilatativer Kardiomyopathie

ZusammenfassungHintergrund und Ziel:Das Verhältnis von Systolen- und Diastolendauer wird als eine wichtige Determinante der Herzfunktion angesehen. Bei Kindern mit dilatativer Kardiomyopathie (DCM) konnte eine abnorme Verkürzung der Diastolendauer beobachtet werden. In der vorliegenden Studie wurde untersucht, ob sich dieser Befund bei Erwachsenen reproduzieren lässt und welches Verhalten der diastolische Anteil des Herzzyklus unter stufenweiser ergometrischer Belastung zeigt.Patienten und Methodik:Die Untersuchung schloss konsekutiv 61 Patienten mit DCM im NYHA-Stadium (New York Heart Association) II–III ein. Bei diesen wurde unter ergometrischer Belastung eine Radionuklidventrikulographie mit hoher zeitlicher Auflösung durchgeführt. Aus der Zeit-Aktivitäts-Kurve wurde neben der linksventrikulären Ejektionsfraktion die Dauer von linksventrikulärer Systole und Diastole abgeleitet. Als Vergleichskollektiv dienten 26 Patienten, bei denen eine normale linksventrikuläre Pumpfunktion mittels Radionuklidangiographie vor geplanter Chemotherapie sichergestellt wurde.Ergebnisse:Der Vergleich der relativen Systolendauer ergab bei Patienten mit DCM bereits in Ruhe eine signifikante Verlängerung gegenüber Herzgesunden (23,9 vs. 21,5 s/min; p = 0,006). Dieser Befund blieb unter maximaler Belastung signifikant (29,2 vs. 26,7 s/min; p = 0,01), obwohl der Herzfrequenzanstieg in der Patientengruppe vermindert war (118 vs. 127/min; p = 0,04). Um den Einfluss der Herzfrequenz auf die Diastolendauer der DCM-Patienten zu eliminieren, wurden die beobachteten Werte mit den rechnerisch aus der Regressionsgleichung Herzgesunder ermittelten Werten verglichen. Dieses Vorgehen bestätigte eine signifikante Verkürzung der Diastolendauer auf maximaler Belastungsstufe und eine Zunahme des Verlusts an diastolischer Zeit pro Herzschlag gegenüber dem Ruhewert.Schlussfolgerung:Patienten mit fortgeschrittener DCM weisen eine abnorme Verkürzung der linksventrikulären Diastolendauer auf. Diese ist unter körperlicher Belastung besonders ausgeprägt und kann die kardiale Effizienz durch Restriktion von ventrikulärer Füllung und Perfusion beeinträchtigen.AbstractBackground and Purpose:Cardiac performance can be characterized in terms of the relative duration of systole and diastole. In pediatric patients with dilated cardiomyopathy (DCM), a disproportionate shortening of left ventricular diastole was observed. The present study was intended to reproduce these findings in an adult patient group and to evaluate exercise-related changes of both time intervals.Patients and Methods:Exercise radionuclide angiography was used in 61 patients with DCM NYHA (New York Heart Association) stage II–III. The phases of the cardiac cycle were derived from a radionuclide time-activity curve with high temporal resolution. The control group consisted of 26 patients referred for ventricular function assessment with radionuclide angiography before cardiotoxic cancer treatment.Results:When the duration of systole was expressed as the product of systolic time and heart rate, DCM patients exhibited a significant increase in left ventricular systolic time at rest (23.9 vs. 21.5 s/min; p = 0.006) and during peak exercise (29.2 vs. 26.7 s/min; p = 0.01). The prolongation of left ventricular systole at peak exercise was evident, although the peak heart rate was significantly lower in the patient group than in the control group (118 vs. 127/min; p = 0.04). In DCM patients the diastolic time loss per beat was further quantified using a regression equation obtained from the healthy control group. A significant shortening of left ventricular diastolic time was confirmed during peak exercise. Furthermore, a progressive loss in diastolic time per beat from rest to peak exercise was noted.Conclusion:Cardiac cycle abnormalities of patients with DCM are characterized by a prolongation of left ventricular systole and an abnormal shortening of left ventricular diastole. The systolic-diastolic mismatch is accentuated during exercise and has the potential to impair the cardiac reserve in these patients by restricting ventricular filling and perfusion.