Mariam Nikfardjam

Right Ventricular Load at Exercise Is a Cause of Persistent Exercise Limitation in Patients With Normal Resting Pulmonary Vascular Resistance After Pulmonary Endarterectomy

BACKGROUND Pulmonary endarterectomy (PEA) provides a potential cure for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, successfully operated patients can continue to suffer from a limitation of exercise capacity, despite normalization of pulmonary vascular resistance (PVR). The purpose of the present study was to explore the cardiopulmonary exercise test (CPET) profile and the pulmonary hemodynamic response to exercise in these patients. METHODS Thirteen successfully operated patients with CTEPH and persistent dyspnea and control subjects underwent a CPET and a right-sided heart catheterization at rest and during exercise. RESULTS The CPET profile of the patients was characterized by mild hyperventilation and decreased peak oxygen uptake (VO2). While there were no differences in resting hemodynamics between patients and control subjects, PVR was higher in the patients after 10 min of exercise (111 ± 46 dynes/s/cm(5) vs 71 ± 42 dynes/s/cm(5), P = .04), and pulmonary arterial compliance (Ca) was lower (5.5 ± 2.3 mL/mm Hg vs 8.1 ± 3.5 mL/mm Hg, P = .048). Ca under exercise correlated with peak VO2 in the patients (R(2) = 0.825, P = .022). CONCLUSIONS After successful PEA, patients with persistent exertional dyspnea display an abnormal pulmonary hemodynamic response to exercise, characterized by increased PVR and decreased Ca. Decreased Ca under exercise is a strong predictor of limited exercise capacity in these patients.

Cell therapy for human ischemic heart diseases: Critical review and summary of the clinical experiences

A decade ago, stem or progenitor cells held the promise of tissue regeneration in human myocardium, with the expectation that these therapies could rescue ischemic myocyte damage, enhance vascular density and rebuild injured myocardium. The accumulated evidence in 2014 indicates, however, that the therapeutic success of these cells is modest and the tissue regeneration involves much more complex processes than cell-related biologics. As the quest for the ideal cell or combination of cells continues, alternative cell types, such as resident cardiac cells, adipose-derived or phenotypic modified stem or progenitor cells have also been applied, with the objective of increasing both the number and the retention of the reparative cells in the myocardium. Two main delivery routes (intracoronary and percutaneous intramyocardial) of stem cells are currently used preferably for patients with recent acute myocardial infarction or ischemic cardiomyopathy. Other delivery modes, such as surgical or intravenous via peripheral veins or coronary sinus have also been utilized with less success. Due to the difficult recruitment of patients within conceivable timeframe into cardiac regenerative trials, meta-analyses of human cardiac cell-based studies have tried to gather sufficient number of subjects to present a statistical compelling statement, reporting modest success with a mean increase of 0.9-6.1% in left ventricular global ejection fraction. Additionally, nearly half of the long-term studies reported the disappearance of the initial benefit of this treatment. Beside further extensive efforts to increase the efficacy of currently available methods, pre-clinical experiments using new techniques such as tissue engineering or exploiting paracrine effect hold promise to regenerate injured human cardiac tissue.

Outcome and functional capacity after prolonged intensive care unit stay.

ZusammenfassungSTUDIENHINTERGRUND: Viele kritisch kranke Patienten, die ihre akute Erkrankung überleben, verbleiben in einem abhängigen Zustand und benötigen für Wochen bis Monate eine Behandlung an der Intensivstation. Die Datenlage betreffend die Spitalsletalität und insbesondere betreffend die Langzeit-Letalität bzw. die -Morbidität bei überlebenden Patienten ist jedoch noch spärlich. Ziel dieser Studie war es, den klinischen Verlauf und Prognosefaktoren bei Langzeit-kritisch kranken Patienten zu untersuchen. METHODEN: Diese retrospektive Beobachtungs-Kohorten-Studie wurde an unserer gemischten kardiologischen 8-Betten-Intensivstation in einem 2200-Betten-Universitätsspital durchgeführt. Patientendaten wurden zwischen dem 1. März 1998 und dem 31. Dezember 2003 analysiert. Patienten mit einer Stations-Aufenthaltsdauer von ≥30 Tagen bildeten die Studiengruppe. Die Evaluation der Morbidität und funktionellen Kapazität wurde mittels Telefoninterview unter Verwendung des Barthel Mobilitäts-Scores durchgeführt. ERGEBNISSE: Die Anzahl der Patienten mit einer Stations-Aufenthaltsdauer ≥30 Tagen betrug 135 (10% der Gesamtpatienten). Diese Gruppe belegte 5962 Bettentage, welches 40,9% der gesamten Bettenkapazität entsprach. Im Vergleich zu Patienten mit einer Stations-Aufenthaltsdauer < 30 Tagen hatten die Patienten in der Langzeitgruppe einen signifikant höheren SAPS II Score innerhalb von 24 Stunden nach Aufnahme (54 [IQR 41–65] vs. 38 [IQR 27–56], p < 0,001). Trendmäßig überwogen die Männer in der Langzeitgruppe (98/135 [82,6%] vs. 782/1215 [64,4%], p = 0,05). Unterschiede in der Intensivstations- und Hospitalsletalität waren nicht signifikant (28/135 [20,7%] vs. 295/1215 [24,3%], p = 0,620, und 46/135 [34,1%] vs. 360/1215 [29,6%], p = 0,285). Die Sterblichkeit bei Patienten, die den Spitalsaufenthalt überlebten, betrug nach einem bzw. nach vier Jahren 14% und 26% in der Kurzzeitgruppe verglichen mit 31% und 61% in der Langzeitgruppe. Ein log-rank-Test erbrachte eine signifikant höhere Überlebenswahrscheinlichkeit in der Kurzzeitgruppe nach Spitalsentlassung (log rank = 34,3, p < 0,001). Eine multivariate Datenanalyse zeigte, dass die Notwendigkeit zu einer Nierenersatztherapie während des Intensivstationsaufenthaltes der einzig unabhängige Prädiktor für das Versterben im Krankenhaus und innerhalb eines Jahres nach Intensivstations-Entlassung war (OR = 2,88; 95%CI 1,12–7,41, p = 0,028 und OR = 3,66, 95%CI 1,36–9,83, p = 0,01). In 28/31 der Langzeit-Überlebenden Patienten (90%) mit einem Intensivstationsaufenthalt ≥30 Tagen zeigte der Barthel Index keine oder nur mäßige Einschränkungen bei Alltagstätigkeiten. SCHLUSSFOLGERUNG: Die Hospitals-Letalität bei kritisch kranken Patienten mit einer Intensivstationsaufenthaltsdauer <30 oder ≥30 Tagen ist vergleichbar. Die Notwendigkeit zu einer Nierenersatztherapie war der einzige unabhängige Prädiktor für das Versterben im Krankenhaus und für die 1-Jahres-Letalität bei Langzeit-Patienten. Kritisch kranke Patienten mit einer Intensivstationsaufenthaltsdauer ≥30 Tagen haben ein hohes und anhaltendes Sterberisiko nach Spitalsentlassung. Dennoch, eine bedeutsame Anzahl von diesen Patienten sind LangzeitÜberlebende mit keinen oder nur mäßigen Einschränkungen bei Alltagstätigkeiten.SummaryBACKGROUND: An important proportion of critically ill patients who survives their acute illness remains in a critical state requiring intensive care management for weeks to months. Nevertheless, data on risk factors for in-hospital mortality and especially for long-term mortality and functional capacity are scarce. This study investigated outcome and prognostic factors in long-term critically ill patients. METHODS: This retrospective observational cohort study was performed at our mixed adult 8-bed cardiologic ICU at a 2200-bed University Hospital. Patient data from our local database connected to an Austrian multicenter program for quality assurance in intensive care were analyzed. Data were collected between March 1st, 1998 and December 31st, 2003. Patients with an ICU stay ≥30 days formed the long-term study group. Morbidity and functional capacity were assessed using the Barthel mobility index in telephone interviews. RESULTS: Patients spending ≥30 days in the ICU numbered 135 (10%) and occupied 5962 bed-days, representing 40.9% of the total bed-days. Compared with patients with an ICU stay <30 days, patients in the long-term group had a significantly higher SAPS II score during the first 24 hours after ICU admission (54 [IQR 41–65] vs. 38 [IQR 27–56], p < 0.001). There was a trend towards male preponderance in the long-term group (98/135 [82.6%] vs. 782/1215 [64.4%], p = 0.05). Differences in ICU and in-hospital mortality were not significant (28/135 (20.7%) vs. 295/1215 (24.3%), p = 0.620 and 46/135 [34.1%] vs. 360/1215 [29.6%], p = 0.285, respectively). After 12 and 48 months, the overall cumulative rates of death in hospital survivors were 14% and 26%, respectively in the short-term ICU group and 31% and 61% in the long-term group. A log-rank test revealed a significantly higher probability of survival in the short-term group after hospital discharge (log rank = 34.3, p < 0.001). Multivariate analysis of hospital survivors and non-survivors in the long-term group showed that the need for renal replacement therapy during the ICU stay was the sole independent predictor for in-hospital death and death within 1 year after ICU discharge (OR = 2.88; 95%CI 1.12–7.41, p = 0.028 and OR = 3.66, 95%CI 1.36–9.83, p = 0.01, respectively). In 28/31 long-term survivors (90%) in the long-term ICU group, the Barthel index indicated no or only moderate disability during daily activities. CONCLUSION: Hospital mortality rates in critically ill patients with a stay <30 or ≥30 days were comparable. The necessity for renal replacement therapy was the sole independent predictor for in-hospital and 1-year mortality in long-term ICU patients. Critically ill patients with a stay ≥30 days have a high and ongoing risk of death after hospital discharge; however, a substantial number of these patients are long-term survivors with no or only moderate disability during daily activities.

Predictive value of plasma plasminogen activator inhibitor‐1 for coronary restenosis: dependence on stent implantation and antithrombotic medication

Summary.  Background: The plasmin activation system is involved in the development of restenosis after percutaneous coronary interventions (PCI). Conflicting data exist concerning the role of plasminogen activator inhibitor‐1 (PAI‐1) and its predictive value for restenosis. Objectives: To evaluate the fibrinolytic response to injury after PCI with or without stent implantation on different antithrombotic medications and its relation to late restenosis. Patients and methods: Eighty consecutive patients with successful PCI without (balloon only; n = 37) or with stent implantation (stent; n = 43) on different antithrombotic regimes (balloon only, aspirin; stent, aspirin/coumadin/dipyridamole vs. aspirin/ticlopidine). Blood samples were taken at baseline and up to 7 days after PCI and PAI‐1 active antigen and tissue plasminogen activator (t‐PA) antigen were determined. Restenosis was angiographically determined after 6 months. Results: PCI increased both t‐PA and PAI‐1 levels (P < 0.001), with a significant prolonged and pronounced increase in stent vs. balloon‐only patients (P < 0.05). Restenosis (stent 26%; balloon 38%) was significantly correlated to an attenuated PAI‐1 increase after 24 h in the ticlopidine group (P = 0.007; restenosis, relative Δ PAI‐1 + 50 ± 28%; non‐restenosis, + 139 ± 50%), but not in the coumadin group. In the balloon‐only group late restenosis (ISR) was associated with a trend for an augmented PAI‐1 increase after 24 h. Conclusions: Coronary stent implantation significantly increases t‐PA and PAI‐1 plasma levels up to 1 week compared with balloon angioplasty alone. ISR in ticlopidine‐treated patients was associated with an attenuated early PAI‐1 active antigen increase. A less than 50% increase 24 h after stent implantation under ticlopidine treatment may identify patients at risk for the development of ISR.

Inhaled iloprost for patients with precapillary pulmonary hypertension and right-side heart failure.

Background Pulmonary hypertension (PH) can lead to right-side heart failure (RHF) and death. There are no therapeutic recommendations for patients experiencing acute RHF in the course of PH. This study aimed to examine the safety and efficacy of inhaled iloprost in patients with precapillary PH and RHF. Methods and Results Between October 2007 and December 2008, 7 patients with precapillary PH and RHF were enrolled. Per protocol, iloprost was inhaled hourly for a minimum of 12 hours during a 24-hour period. The starting dose of 2.5 μg was increased hourly by 2.5 μg as long as the increases were tolerated. Safety and efficacy were determined by continuous invasive monitoring of systemic and pulmonary hemodynamic parameters. Systemic pressures remained stable during inhalation (66.1 ± 6.9 mm Hg at baseline and 69.1 ± 6.4 mm Hg immediately after inhalation therapy, P = 0.48). Cardiac index increased from 2.4 ± 0.7 L/min/m2 to 2.9 ± 0.9 L/min/m2 (P = .008). Pulmonary vascular resistance decreased from 634.6 ± 218.3 dyn·s·cm−5 to 489.6 ± 173.8 dyn·s·cm−5 (P = .044), and N-terminal B-type natriuretic peptide levels decreased from 13,591 ± 10,939 pg/mL to 9,944 ± 8,569 pg/mL (P = .051). Conclusion Blood pressure-guided hourly inhalation of iloprost may offer a safe and effective strategy for the treatment of PH patients with RHF.

Role of amiodarone on the systemic inflammatory response induced by cardiac surgery : proinflammatory actions

Objectif On a demontre que l’amiodarone (AMIO), un medicament anti-arythmique tres utilise, reduit l’incidence de fibrillation auriculaire apres la chirurgie cardiaque et qu’il exerce une action immunomodulatrice in vitro ainsi que des effets pronflammatoires in vivo. Cette etude a observe les proprietes immunomodulatrices de l’AMIO dans la reaction inflammatoire provoquee par la chirurgie cardiaque avec circulation extracorporelle (CEC).PurposeAmiodarone (AMIO), a widely used anti-arrhythmic drug, has been shown to reduce the incidence of atrial fibrillation after cardiac surgery and also to exert immunomodulatory actionsin vitro and proinflammatory effectsin vivo. The present study investigated the immunomodulatory properties of AMIO in the inflammatory response induced by cardiac surgery with cardiopulmonary bypass (CPB).MethodsIn this double-blind, placebo-controlled trial, 20 patients undergoing elective coronary artery bypass graft were randomized to receive placebo or AMIO 600 mg·day-1 orally for seven days before surgery and 45 mg hr-1 intravenously for 48 hr postoperatively. Plasma levels of the proinflammatory markers Ceactive protein (CRP), fibrinogen (FBG), tumour necrosis factor (TNF)-α, interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and the antiinflammatory marker IL-10, were compared before and after surgery.ResultsNinety-six hours after start of surgery, plasma levels of FBG had more than doubled (2.2 ± 0.5-fold increase, P < 0.0001). Overall, FBG formation was significantly increased in the AMIO group (P = 0.048). Monocyte chemoattractant protein 1 secretion transiently increased four hours after start of surgery (6.6 ± 4.5-fold increase) but rapidly declined thereafter, (P < 0.0001). There was a trend toward higher MCP-1 plasma concentrations in the AMIO group (P = 0.13). The plasma levels of CRP, TNF-α, IL-6 and Il-10 changed significantly over time, but were not altered by AMIO treatment.ConclusionIn the inflammatory response induced by cardiac surgery with CPB, our data suggest that AMIO treatment is associated with a selective trend toward proinflammatory actions.RésuméObjectifOn a démontré que l’amiodarone (AMIO), un médicament anti-arythmique très utilisé, réduit l’incidence de fibrillation auriculaire après la chirurgie cardiaque et qu’il exerce une action immunomodulatrice in vitro ainsi que des effets pronflammatoires in vivo. Cette étude a observé les propriétés immunomodulatrices de l’AMIO dans la réaction inflammatoire provoquée par la chirurgie cardiaque avec circulation extracorporelle (CEC).MéthodeDans cette étude à double insu et contrôlée par placebo, vingt patients devant subir un pontage aortocoronarien ont été randomisés à recevoir oralement soit un placebo, soit de l’AMIO 600 mg·jour-1 les sept jours précédant la chirurgie et 45 mg·h-1 en intraveineux durant les 48 h suivant l’opération. Les niveaux plasmatiques des marqueurs pro-inflammatoires suivants ont été comparés avant et après l’opération: protéine C-réactive (CRP), fibrinogène (FBG), facteur nécrosant des tumeurs (TNF)- α, interleukine (IL)-6 et protéine chimioattractive monocytaire (MCP1), et le marqueur antinflammatoire IL-10.RésultatsLes niveaux plasmatiques de FBG avaient plus que doublé 96 h après le début de la chirurgie (augmentation par 2,2 ± 0,5 fois, P < 0,0001). De façon générale, la formation de FBG s’est accrue de façon significative dans le groupe AMIO (P = 0,048). La sécrétion de la MCP-1 a momentanément augmenté quatre heures après le début de la chirurgie (de 6,6 ± 4,5 fois), mais a rapidement diminué ensuite (P < 0,0001). Une tendance vers des concentrations plasmatiques de MCP-1 plus élevées a été observée dans le groupe AMIO (P = 0,13). Les niveaux plasmatiques de CRP, TNF-α, IL-6 et IL-10 se sont modifiés de façon significative durant le temps de l’étude, mais le traitement à l’AMIO ne les a pas influencés.ConclusionDans le cas de la réaction inflammatoire provoquée par une chirurgie cardiaque avec CEC, nos données suggèrent que le traitement à l’AMIO est associé à une tendance sélective vers des propriétés pronflammatoires.

Premature compared with late onset of coronary artery disease: young patients show a severe defect in fibrinolytic response to venous occlusion.

Inflammatory processes play a role in the onset of acute cardiovascular events associated with activation of the coagulation system whereas the fibrinolytic system may prevent local thrombus formation. We compared 25 patients with premature coronary artery disease (CAD) (first ST-elevation myocardial infarction, < 55 years old) with 25 sex-matched patients older than 55 years at their first myocardial infarction. Six months after the acute event, patients with late onset of CAD showed a significantly higher increase of tissue-type plasminogen activator activity during venous occlusion compared with patients with premature CAD (P < 0.005). Prothrombin fragment 1+2 was higher in patients with late-onset CAD (P < 0.05), whereas the inflammatory markers C-reactive protein and soluble intercellular cell adhesion molecule-1 were not different in both groups. A multivariate analysis including cardiovascular risk factors showed that the tissue-type plasminogen activator response to venous occlusion was independently associated with patient age at onset of first ST-elevation myocardial infarction. Although in our series high age was associated with a prothrombotic state, a high fibrinolytic capacity might have some beneficial effect and contribute to a delayed onset of adverse cardiovascular events in these patients.

Cost-effectiveness of percutaneous coronary intervention with drug-eluting stents in patients with multivessel coronary artery disease compared to coronary artery bypass surgery five-years after intervention

Cost‐effectiveness of percutaneous coronary intervention (PCI) using drug‐eluting stents (DES), and coronary artery bypass surgery (CABG) was analyzed in patients with multivessel coronary artery disease over a 5‐year follow‐up.

Decreasing Incidence of Critical Limb Ischemia After Intra-aortic Balloon Pump Counterpulsation

The authors investigated the incidence of critical limb ischemia (CLI) in 187 patients with intra-aortic balloon pump (IABP) support during a 6-year study period and determined risk factors and long-term outcome (median 5 years) after discharge from a cardiac intensive care unit. Cardiogenic shock following acute myocardial infarction was the predominant cause of IABP support. CLI occurred in 10% of the patients after IABP implantation. Nevertheless, in light of the overall high mortality in this patient population, CLI seems not a primary concern. Furthermore, its incidence significantly decreased during recent years. Duration of IABP support was a significant predictor for CLI.

Rôle de l’amiodarone sur la réaction inflammatoire systémique provoquée par la chirurgie cardiaque : Sactions pro-inflammatoires

Objectif On a demontre que l’amiodarone (AMIO), un medicament anti-arythmique tres utilise, reduit l’incidence de fibrillation auriculaire apres la chirurgie cardiaque et qu’il exerce une action immunomodulatrice in vitro ainsi que des effets pronflammatoires in vivo. Cette etude a observe les proprietes immunomodulatrices de l’AMIO dans la reaction inflammatoire provoquee par la chirurgie cardiaque avec circulation extracorporelle (CEC).PurposeAmiodarone (AMIO), a widely used anti-arrhythmic drug, has been shown to reduce the incidence of atrial fibrillation after cardiac surgery and also to exert immunomodulatory actionsin vitro and proinflammatory effectsin vivo. The present study investigated the immunomodulatory properties of AMIO in the inflammatory response induced by cardiac surgery with cardiopulmonary bypass (CPB).MethodsIn this double-blind, placebo-controlled trial, 20 patients undergoing elective coronary artery bypass graft were randomized to receive placebo or AMIO 600 mg·day-1 orally for seven days before surgery and 45 mg hr-1 intravenously for 48 hr postoperatively. Plasma levels of the proinflammatory markers Ceactive protein (CRP), fibrinogen (FBG), tumour necrosis factor (TNF)-α, interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and the antiinflammatory marker IL-10, were compared before and after surgery.ResultsNinety-six hours after start of surgery, plasma levels of FBG had more than doubled (2.2 ± 0.5-fold increase, P < 0.0001). Overall, FBG formation was significantly increased in the AMIO group (P = 0.048). Monocyte chemoattractant protein 1 secretion transiently increased four hours after start of surgery (6.6 ± 4.5-fold increase) but rapidly declined thereafter, (P < 0.0001). There was a trend toward higher MCP-1 plasma concentrations in the AMIO group (P = 0.13). The plasma levels of CRP, TNF-α, IL-6 and Il-10 changed significantly over time, but were not altered by AMIO treatment.ConclusionIn the inflammatory response induced by cardiac surgery with CPB, our data suggest that AMIO treatment is associated with a selective trend toward proinflammatory actions.RésuméObjectifOn a démontré que l’amiodarone (AMIO), un médicament anti-arythmique très utilisé, réduit l’incidence de fibrillation auriculaire après la chirurgie cardiaque et qu’il exerce une action immunomodulatrice in vitro ainsi que des effets pronflammatoires in vivo. Cette étude a observé les propriétés immunomodulatrices de l’AMIO dans la réaction inflammatoire provoquée par la chirurgie cardiaque avec circulation extracorporelle (CEC).MéthodeDans cette étude à double insu et contrôlée par placebo, vingt patients devant subir un pontage aortocoronarien ont été randomisés à recevoir oralement soit un placebo, soit de l’AMIO 600 mg·jour-1 les sept jours précédant la chirurgie et 45 mg·h-1 en intraveineux durant les 48 h suivant l’opération. Les niveaux plasmatiques des marqueurs pro-inflammatoires suivants ont été comparés avant et après l’opération: protéine C-réactive (CRP), fibrinogène (FBG), facteur nécrosant des tumeurs (TNF)- α, interleukine (IL)-6 et protéine chimioattractive monocytaire (MCP1), et le marqueur antinflammatoire IL-10.RésultatsLes niveaux plasmatiques de FBG avaient plus que doublé 96 h après le début de la chirurgie (augmentation par 2,2 ± 0,5 fois, P < 0,0001). De façon générale, la formation de FBG s’est accrue de façon significative dans le groupe AMIO (P = 0,048). La sécrétion de la MCP-1 a momentanément augmenté quatre heures après le début de la chirurgie (de 6,6 ± 4,5 fois), mais a rapidement diminué ensuite (P < 0,0001). Une tendance vers des concentrations plasmatiques de MCP-1 plus élevées a été observée dans le groupe AMIO (P = 0,13). Les niveaux plasmatiques de CRP, TNF-α, IL-6 et IL-10 se sont modifiés de façon significative durant le temps de l’étude, mais le traitement à l’AMIO ne les a pas influencés.ConclusionDans le cas de la réaction inflammatoire provoquée par une chirurgie cardiaque avec CEC, nos données suggèrent que le traitement à l’AMIO est associé à une tendance sélective vers des propriétés pronflammatoires.