C.F. Opitz

Impairment of Ventilatory Efficiency in Heart Failure Prognostic Impact

BACKGROUNDnImpairment of ventilatory efficiency in congestive heart failure (CHF) correlates well with symptomatology and contributes importantly to dyspnea.nnnMETHODS AND RESULTSnWe investigated 142 CHF patients (mean NYHA class, 2.6; mean maximum oxygen consumption [VO(2)max], 15.3 mL O(2) x kg(-1) x min(-1); mean left ventricular ejection fraction [LVEF], 27%). Patients were compared with 101 healthy control subjects. Cardiopulmonary exercise testing was performed, and ventilatory efficiency was defined as the slope of the linear relationship of V(CO(2)) and ventilation (VE). Results are presented in percent of age- and sex-adjusted mean values. Forty-four events (37 deaths and 7 instances of heart transplantation, cardiomyoplasty, or left ventricular assist device implantation) occurred. Among VO(2)max, NYHA class, LVEF, total lung capacity, and age, the most powerful predictor of event-free survival was the VE versus V(CO(2)) slope; patients with a slope </=130% of age- and sex-adjusted normal values had a significantly better 1-year event-free survival (88.3%) than patients with a slope >130% (54.7%; P<0.001).nnnCONCLUSIONSnThe VE versus V(CO(2)) slope is an excellent prognostic parameter. It is easier to obtain than parameters of maximal exercise capacity and is of higher prognostic importance than VO(2)max.

Effects of Iloprost Inhalation on Exercise Capacity and Ventilatory Efficiency in Patients With Primary Pulmonary Hypertension

BACKGROUNDnThe continuous infusion of prostacyclin has been shown to improve exercise capacity and survival in patients with primary pulmonary hypertension (PPH). Inhalation of iloprost, a stable analog of prostacyclin, might be an alternative therapy for PPH, selectively acting on the pulmonary vascular bed through ventilation-matched alveolar deposition of the drug. We investigated the short-term effects of iloprost inhalation on exercise capacity and gas exchange in patients with PPH.nnnMETHODS AND RESULTSnIn 11 patients with PPH, we performed 2 consecutive cardiopulmonary exercise tests before and after the inhalation of 17 microgram of iloprost. Patients had marked pulmonary hypertension (mean pulmonary artery pressure 65 mm Hg), and inhalation resulted in a decrease in pulmonary vascular resistance (1509 versus 1175 dyne. s(-1). cm(-5), P<0.05). Arterial blood gases remained unchanged (PaO(2) 69.3 versus 66.8 mm Hg; PaCO(2) 29.6 versus 28.8 mm Hg). Iloprost significantly (P<0.05) improved exercise duration (379 versus 438 seconds), peak oxygen uptake (12.8 versus 14.2 mL. kg(-1). min(-1)), VE-versus-V CO(2) slope (58 versus 51.4).nnnCONCLUSIONSnThe present data show that iloprost inhalation exerts pulmonary vasodilatation and improves symptoms and exercise capacity in patients with PPH. The data also suggest that iloprost inhalation is a suitable treatment for PPH. Whether these effects are maintained during long-term treatment and are paralleled by improvement in prognosis remains to be determined.

Reference values for cardiopulmonary exercise testing in healthy volunteers: the SHIP study

Cardiopulmonary exercise testing (CPET) is a widely applied clinical procedure. The aim of the present study was to acquire a comprehensive set of reference values for cardiopulmonary responses to exercise and to evaluate possible associations with sex, age and body mass index (BMI). A standardised progressive incremental exercise protocol on a cycle ergometer was applied to 1,708 volunteers of a cross-sectional epidemiologic survey, called “Study of Health in Pomerania”. Individuals with cardiopulmonary disorders, or echocardiographic or lung function pathologies, were excluded. The influence of potential confounding factors, such as smoking, taking β-blockers, hypertension, diastolic dysfunction, BMI and physical activity, were analysed for their influencing power. Reference values of CPET parameters were determined by regression analyses. Of the volunteers, 542 current smokers and obese individuals were excluded for not being representative of a healthy population. The final sample size was 534 (253 males), with age 25–80u2005yrs. The current study provides a representative set of reference values for CPET parameters based on age and weight. Sex and age have a significant influence on exercise parameters. While addressing the problem of a selection bias, the current study provides the first comprehensive set of reference values obtained in a large number of healthy volunteers within a population-based survey.

Assessment of the vasodilator response in primary pulmonary hypertension Comparing prostacyclin and iloprost administered by either infusion or inhalation

AIMSnTo directly compare the differential effects of oxygen, prostacyclin and iloprost (aerosolized and intravenous) in primary pulmonary hypertension.nnnMETHODS AND RESULTSnTwenty-one patients with severe primary pulmonary hypertension underwent right heart catheterization following oxygen inhalation, inhalation of aerosolized iloprost, intravenous prostacyclin or intravenous iloprost. The stability of the iloprost solution was tested for up to 4 weeks. Oxygen slightly decreased pulmonary vascular resistance. Intravenous prostacyclin (7.2+/-3.4 ng kg(-1) min(-1)) reduced pulmonary (1772+/-844 vs 1325+/-615 dyn s cm(-5), P<0.001) and systemic vascular resistance, and arterial and right atrial pressure, while cardiac output increased. Iloprost inhalation diminished pulmonary (1813+/-827 vs 1323+/-614 dyn s cm(-5), P<0.001) and systemic vascular resistance, and pulmonary artery (58+/-12 vs 50+/-12 mmHg,P<0.001) and right atrial pressure, while cardiac output increased. With intravenous iloprost (1.2+/-0.5 ng kg(-1) min(-1), n=8) a decrease in pulmonary (2202+/-529 vs 1515+/-356 dyn s cm(-5), P<0.05) and systemic vascular resistance and right a trial pressure occurred while cardiac output increased. Iloprost solution remained stable for 33 days while losing <10% (4 degrees C) of its active drug concentration.Conclusions Intravenous iloprost and prostacyclin have very similar haemodynamic profiles. In contrast, only inhaled iloprost exerted selective pulmonary vasodilation, reducing pulmonary vascular resistance and pulmonary artery pressure without systemic vasodilation. The longer half-life and extended stability despite lower costs render iloprost an attractive alternative to chronic prostacyclin treatment in primary pulmonary hypertension.

Acetylcholine but not sodium nitroprusside exerts vasodilation in pulmonary hypertension secondary to chronic congestive heart failure.

BACKGROUNDnReduced endothelium-dependent vasodilation contributes to the development of pulmonary hypertension in chronic congestive heart failure (CHF). We investigated pulmonary endothelium-dependent and independent vasodilation in patients with CHF.nnnMETHODSnWe studied 42 patients with CHF (age 55 +/- 10, NYHA Classes II-III, left ventricular ejection fraction 27 +/- 10%, mean PAP 29 +/- 12 mmHg). The endothelial vasodilator capacity of pulmonary resistance vessels was assessed by the infusion of acetylcholine into a pulmonary artery branch while measuring the blood flow velocity with a Doppler flow wire. For comparison endothelium-independent vasodilation was measured with the response to sodium nitroprusside. The conductance vessel diameter (4.4 +/- 0.2 mm) was determined by intravascular ultrasound. Acetylcholine was administered at concentrations of 10(-6) to 10(-4) mol/l, sodium nitroprusside was administered at concentrations of 0.125 and 0.25 microg/kg per min. The effects on conductance vessel diameter were investigated in 12 patients by the measurement of diameter and flow velocity following the administration of acetylcholine and sodium nitroprusside.nnnRESULTSnAcetylcholine markedly increased blood flow velocity (+39 +/- 7% at 10(-4) mol/l; p < .05). This correlated with the baseline PAP (r = 0.58; p < .05) and pulmonary vascular resistance (r = 0.58; p < .05). Sodium nitroprusside caused a small increase in the flow velocity (5 +/- 2% at 0.125, 12 +/- 4% at 0.25 microg/kg per minute; p < .05) that was accompanied by systemic vasodilation. The conductance vessel diameter was unchanged after acetylcholine was administered and was only marginally decreased after the administration of sodium nitroprusside.nnnCONCLUSIONSnIn CHF acetylcholine reveals preserved receptor-mediated endothelial vasodilation, that is positively correlated to pulmonary hypertension, and cannot be reproduced by sodium nitroprusside.

Resting Alveolar Gas Tensions as a Mortality Prognosticator in Chronic Heart Failure

BACKGROUNDnIncreased end-tidal oxygen (ET-O(2)) and decreased end-tidal carbon dioxide (ET-CO(2)) gas tensions are noninvasively measurable correlates of ventilatory inefficiency, leading to increased ventilatory requirements relative to gas exchange among patients with chronic heart failure (CHF). We investigated the prognostic value of ET-O(2) and ET-CO(2) as predictors of CHF mortality.nnnMETHODSnWe measured resting ET-O(2) and ET-CO(2) electrochemically in 134 patients with symptomatic CHF in the supine position. We used Kaplan-Meier analysis, Cox proportional hazard models, and receiver operating characteristic curves to test our hypothesis.nnnRESULTSnAt a median follow-up of 16.5 months, 32 patients had died. ET-O(2) levels were increased (P = .001) and ET-CO(2) levels decreased (P = .002) with increased New York Heart Association class (I-IV). Survivors showed lower ET-O(2) (121 vs 118 mm Hg; P = .021) and higher ET-CO(2) (33.2 vs 32.1 mm Hg; P = .032) levels than nonsurvivors. Patients with ET-O(2) values ≥121 mm Hg and/or ET-CO(2) values <31 mm Hg had an increased risk of death with hazard ratios of 2.93 (95% confidence interval [CI], 1.43-6.01) and 2.47 (95% CI, 1.23-4.97), respectively. Kaplan-Meier estimates for follow-up mortality with ET-O(2) ≥121 mm Hg and/or ET-CO(2) <31 mm Hg were 83.8% (vs 60.1%; P = .0014) and 80.3% (vs 60.2%; P = .0061), respectively. Areas under the receiver operating characteristic curves for prediction of death with ET-O(2) and ET-CO(2) were both significant and similar to that of echocardiographic left ventricular function.nnnCONCLUSIONSnIn CHF, high levels of ET-O(2) and low levels of ET-CO(2) are associated with increased mortality. We suggest that the measurements may be useful prognostic markers for risk stratification.

Pulmonary Interstitial and Vascular Abnormalities Following Cardiac Transplantation

Impairment of pulmonary diffusion (KCO) is frequently seen in patients following orthotopic heart transplantation (HTX). To assess potential histomorphological pulmonary causes of KCO abnormalities, we evaluated tissue samples from 73 patients who succumbed after HTX in the presence of KCO abnormalities, excluding those with infectious or primary pulmonary causes of death. In 97% of subjects, we observed considerable histomorphological changes in interstitial or vascular tissue or both. In 32% of samples, interstitial changes (eg, cell proliferation or fibrosis) were accompanied by vascular abnormalities, whereas more than two-thirds of the patients showed alterations in one of the two conditions. Hemosiderin-laden macrophages were observed in 48% of subjects. The mean alveolar-capillary wall thickness was significantly increased to 9.9 +/- 4.2 mum. The time of survival after HTX was not correlated with the incidence of pathological findings. The described vascular and interstitial pulmonary changes as well as the increased membrane thickness may cause the persistent impairment of KCO after HTX.

Medikamentöse Behandlung von Patienten mit chronischer Pulmonaler Hypertonie

Zusammenfassung Die Betreuung der Patienten mit Pulmonaler Hypertonie (PHT) umfasst die Beratung zur entsprechend des klinischen Bildes notwendigen körperlichen Schonung und den im Einzelfall möglichen chirurgischen und interventionellen Maßnahmen. Bei der Mehrzahl der Patienten wird als therapeutische Option lediglich eine medikamentöse Behandlung gegeben sein. Über alle Formen der PHT besteht diese aus Diuretika, Glykosiden und einer oralen Antikoagulation. Bei hypoxämischen Patienten sollte frühzeitig eine konsequente Sauerstoff-Langzeit-Behandlung eingeleitet werden. Bei unzureichender Stabilisierung und bestehender Funktionseinschränkung unter dieser Basistherapie werden unterschiedliche Vasodilatatoren zum Einsatz gebracht. Die Datenlage zur Anwendung bei PHT der aus mehreren Substanzgruppen (u.a. Kalziumkanalblocker und Prostanoide) stammenden Dilatatoren ist unterschiedlich. Dieses trifft auch für die verschiedenen in jüngster Zeit entwickelten Applikationsformen der Prostanoide zu. Durch die Einführung neuere Medikamente (u.a. Endothelin-Rezeptor-Antagonisten, Phosphodiesterase-Hemmer) sind in Zukunft weitere Fortschritte auf dem Gebiet der konservativen Behandlung der Patienten mit PHT zu erwarten.Summary The treatment of patients with pulmonary hypertension (PHT) includes advising them to avoid physical exertion and, in individual cases, surgical and interventional procedures. In the majority of patients only medicamentous treatment is indicated. For all forms of PHT this includes the administration of diuretics, glycosides and oral anticoagulation. In hypoxemic patients long-term oxygen treatment should be initiated at an early stage. If this basic therapy does not lead to satisfactory stabilization and existing physical limitations remain, various vasodilators may be administered. The data available on the use in PHT patients of different groups of substances, including calcium channel blockers and prostanoids, vary. This also applies to the different forms of prostanoid administration developed recently. Through the introduction of new drugs (e.g., endothelin receptor antagonists, phosphodiesterase inhibitors), further progress in the area of conservative treatment of patients with PHT may be expected in the future.

Prognosis in pulmonary arterial hypertension

To the Editors:nnWe read with interest the article by Humbert et al. 1 on the difference in prognosis in prevalent versus incident cohorts of patients with pulmonary arterial hypertension (PAH). The study highlights a survival bias in the prevalent cohort due to under-representation of more severely ill patients that might have died before inclusion in the registry. Humbert et al. 1 subsequently found a 1-yr and 3-yr survival rate of 89% and 69% for the prevalent cohort and 89% and 55% for the incident cohort of patients with idiopathic, familiar or anorexigen-associated PAH, respectively.nnAlthough we acknowledge that prevalent cohorts have a selection bias, it is surprising that this does not refer to a difference in mortality at 1-yr but only later during follow-up. If selection of the sickest patients would account for better survival one would expect the same phenomenon in the incident cohort. This would lead to …

Untersuchung mit dem Rechtsherzkatheter bei pulmonaler Hypertonie

ZusammenfassungVor genau 80xa0Jahren wurde in Deutschland die erste Untersuchung mit dem Rechtsherzkatheter (RHK) durchgeführt. Anfänglich zur Diagnostik bei Patienten mit erworbenen und angeborenen Herzfehlern genutzt, wird heute der RHK zusätzlich in der Intensivmedizin angewendet. Trotz der Entwicklung nichtinvasiver, bildgebender Verfahren ist auch heute die Diagnosestellung einer pulmonalen Hypertonie (PH) nur nach RHK-Diagnose akzeptiert. Während einer solchen Untersuchung wird häufig auch eine Testung der Gefäßreagibilität durchgeführt.Die Indikationen, technischen Besonderheiten sowie mögliche Komplikationen bei der Durchführung des RHK werden beschrieben. Zur Interpretation der RHK-Messwerte müssen das gesamte klinische Bild des Patienten sorgfältig einbezogen und mögliche Fehlerquellen berücksichtigt werden. Neben der Erstdiagnostik ist bei Patienten mit PH auch bei unklarer Verschlechterung der klinischen Situation sowie bei diskrepanten Befunden aus der nichtinvasiven Diagnostik eine RHK-Untersuchung im Verlauf sinnvoll.AbstractEighty years ago, the first right heart catheterization (RHC) was accomplished in Germany. Initially developed to assess patients with congenital and acquired heart defects, its spectrum of use has widened. Thus, RHC plays an important role in intensive care medicine and cardiopulmonary surgery. Despite recent progress in noninvasive hemodynamic monitoring facilities, RHC is still the gold standard for diagnosing pulmonary hypertension (PH). Furthermore, in this indication RHC is frequently used to assess pulmonary vasoresponsiveness.This overview emphasizes the indications, technical needs, and possible complications of RHC. Because RHC may be a source of technical and interpretational errors, the obtained results need to be assessed within the clinical picture. In PH patients, RHC does have unquestionable value in confirming the diagnosis as well as in assessing clinical worsening, and discrepancies between noninvasive investigations and the clinical picture can be clarified.