Kurt Kochsiek

Myocardial Phosphocreatine-to-ATP Ratio Is a Predictor of Mortality in Patients With Dilated Cardiomyopathy

BACKGROUND In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class. METHODS AND RESULTS Thirty-nine patients with dilated cardiomyopathy were followed up for 928+/-85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal phosphocreatine-to-ATP ratio (>1.60; mean+/-SE, 1.98+/-0.07; n=19; healthy volunteers: 1.94+/-0.11, n=30) and one with a reduced phosphocreatine-to-ATP ratio (<1.60; 1.30+/-0.05; n=20). At re-evaluation (mean, 2.5 years), 8 of 20 patients with reduced phosphocreatine-to-ATP ratios had died, all of cardiovascular causes (total and cardiovascular mortality, 40%). Of the 19 patients with normal phosphocreatine-to-ATP ratios, 2 had died (total mortality, 11%), one of cardiovascular causes (cardiovascular mortality, 5%). Kaplan-Meier analysis showed significantly reduced total (P=.036) and cardiovascular (P=.016) mortality for patients with normal versus patients with low phosphocreatine-to-ATP ratios. A Cox model for multivariate analysis showed that the phosphocreatine-to-ATP ratio and NYHA class offered significant independent prognostic information on cardiovascular mortality. CONCLUSIONS The myocardial phosphocreatine-to-ATP ratio, measured noninvasively with 31P-MR spectroscopy, is a predictor of both total and cardiovascular mortality in patients with dilated cardiomyopathy.

Effect of Intravenous and Intracoronary Nifedipine on Coronary Blood Flow and Myocardial Oxygen Consumption

The effect of intravenous and intracoronary nifedipine on coronary sinus blood flow, coronary vascular resistance, and myocardial oxygen consumption was studied in 20 patients with coronary artery disease. An intravenous infusion of 1.0 mg nifedipine resulted in a decrease in mean aortic pressure, an increase in heart rate and coronary blood flow, and no significant change in myocardial, oxygen consumption. In contrast, the intracoronary injection of 0.1 mg nifedipine led to a moderate reduction in mean aortic pressure, no change in heart rate, an increase in coronary blood flow, and a significant reduction in myocardial oxygen consumption. During rapid atrial pacing before and approximately 6 minutes after the intracoronary nifedipine injection, coronary blood flow and myocardial oxygen consumption reached identical levels. Thus, only intracoronary injection of nifedipine increases coronary flow in the presence of reduced myocardial oxygen consumption. After intravenous administration, reflex tachycardia counteracts the direct myocardial effect of nifedipine and the potential oxygen-saving effect of afterload reduction. There is no evidence of a prolonged oxygen-sparing effect after cessation of the immediate effects.

Clinical cardiac magnetic resonance spectroscopy - present state and future directions

MR spectroscopy opens a window to the non-invasive evaluation of various aspects of cardiac metabolism. Experimentally, the method has extensively been used since 1970’s. 31P-MR allows the registration of cardiac high-energy phosphate metabolism to non-invasively estimate the energetic state of the heart: ATP, phosphocreatine, inorganic phosphate, monophosphate esters and intracellular pH can all be quantitated. In conjunction with extracellular shift reagents such as [DyTTHA]3- or [TmDOTP]5-, 23Na- and 39K-MR allow the measurement of intra- and extra-cellular cation pools. 1H-MR spectroscopy allows the detection of a large number of metabolites such as, e.g. creatine, lactate, or carnitine.

Coronary hemodynamic and metabolic effects of nifedipine in patients with coronary artery disease treated with beta-blocking drugs

In humans, reflex sympathetic nerve activation modulates the direct cardiac action of nifedipine after systemic administration and results in a positive chronotropic and inotropic response. The coronary hemodynamic and metabolic effects of nifedipine were evaluated after propranolol-induced acute beta-receptor blockade in 12 patients with angiographically documented coronary artery disease. The intravenous injection of propranolol led to a decrease in heart rate, coronary blood flow and myocardial oxygen consumption and an increase in coronary vascular resistance and the coronary arteriovenous oxygen difference. Mean aortic pressure did not change. The subsequent intravenous administration of nifedipine resulted in a transient increase in coronary blood flow and a reduction in coronary vascular resistance and the coronary arteriovenous oxygen difference and a sustained decrease in mean aortic pressure and myocardial oxygen consumption without significant changes in heart rate. Thus, in the presence of beta-receptor blockade, the positive chronotropic response to nifedipine is attenuated and nifedipine reduces myocardial oxygen consumption significantly. The vasodilatory effect of nifedipine is maintained and a potential propranolol-related inappropriate vasoconstriction may be reversed. The combination of nifedipine and beta-receptor blocking agents may be useful in the treatment of patients with both effort-induced angina and angina related to changes in coronary vasomotor tone.

Exogenous Surfactant Application in Respiratory Failure due to Chronic Obstructive Pulmonary Disease

Recent results of basic research on regulation of surfactant secretion and surfactant physiology not only in the alveolus but also in peripheral small airways allow the conclusion that disorders in surfactant homeostasis may contribute to the pathophysiology of airway obstruction and hyperinflation. We therefore hypothesized that patients with respiratory failure due to obstructive lung disease may benefit from exogenous surfactant. Here we report a case that indicates the clinical situation to be considered for treatment with exogenous surfactant. The benefit for the patient was successful weaning from the ventilator. Improvements in effective compliance, resistance and blood gas parameters were observed following surfactant application.

Left Ventricular Function During VVI and DVI Pacing at Different Rates as Assessed by M-Mode and Two-Dimensional Echocardiography, Gated Single Photon Emission Computerized Tomography (GASPECT) and Thermodilution

The influence of heart rate and pacing mode (ventricular pacing (VVI) versus atrial synchronous pacing (DVI)) on left ventricular volumes, cardiac index (CI) and ejection fraction (EF) was analyzed with M-mode and two-dimensional echocardiography, gated single photon emission computerized tomography (GASPECT) and compared to stroke volume indices (SVI) and CI obtained by simultaneous thermodilution measurements.