Jörg Honold

Transcoronary Transplantation of Functionally Competent BMCs Is Associated With a Decrease in Natriuretic Peptide Serum Levels and Improved Survival of Patients With Chronic Postinfarction Heart Failure: Results of the TOPCARE-CHD Registry

Although intracoronary administration of bone marrow–derived mononuclear progenitor cells (BMCs) may be associated with improved cardiac function in patients with chronic postinfarction heart failure, the impact on prognosis and clinical outcome of these patients is unknown. To identify potential predictors for a favorable clinical outcome, we assessed natriuretic peptide serum levels as objective markers of heart failure and the occurrence of cardiac death in relation to functional capacity of the infused cells in a consecutive series of 121 patients with chronic ischemic heart disease treated with intracoronary infusion of BMCs. Our analyses show that both N-terminal pro–brain natriuretic peptide (NT-proBNP) and N-terminal pro–atrial natriuretic peptide (NT-proANP) serum levels were significantly reduced in patients with established postinfarction heart failure 3 months after transcoronary progenitor cell administration. NT-proBNP serum levels greater than or equal to median (735 pg/mL) at baseline and a high number of infused progenitor cells with colony-forming capacity were the only independent predictors of a favorable response 3 months after intracoronary administration of BMCs. During extended clinical follow-up (577±442 days), a total of 14 deaths occurred in the overall patient population. Kaplan–Meier curves for both all cause and cardiac mortality showed that patients receiving a higher number of colony-forming cells were significantly less likely to die than those patients receiving low numbers of colony-forming cells (P=0.01). Most importantly, infusion of a high number of cells with colony-forming capacity was associated with a complete abrogation of increased mortality in patients with elevated NT-proBNP serum levels (≥735 pg/mL; median) at baseline (P<0.001). Taken together, our results show that patients with objective evidence of postinfarction heart failure demonstrate a significant reduction of both NT-proBNP and NT-proANP serum levels within 3 months following intracoronary infusion of BMCs. Importantly, infusion of progenitor cells with a high functional capacity is associated with a significantly lower mortality during further follow-up.

A Pilot Trial to Assess Potential Effects of Selective Intracoronary Bone Marrow–Derived Progenitor Cell Infusion in Patients With Nonischemic Dilated Cardiomyopathy Final 1-Year Results of the Transplantation of Progenitor Cells and Functional Regeneration Enhancement Pilot Trial in Patients With Nonischemic Dilated Cardiomyopathy

Background— Intracoronary administration of bone marrow–derived progenitor cells (BMC) was shown to improve coronary microvascular function in ischemic heart disease. Because coronary microvascular dysfunction is implicated in the pathogenesis and prognosis of nonischemic dilated cardiomyopathy (DCM), we investigated the effects of intracoronary BMC administration in patients with DCM. Methods and Results— Intracoronary infusion of BMC was performed in 33 patients with DCM by using an over-the-wire balloon catheter. Left ventricular contractility at baseline and after 3 months was assessed by analysis of left ventricular angiograms. Coronary hemodynamics were determined by intracoronary Doppler wire measurements. After 3 months, regional wall motion of the target area (contractility from −1.08±0.39 to −0.97±0.47 SD/chord, P =0.029) and global left ventricular ejection fraction (from 30.2±10.9 to 33.4±11.5%, P <0.001) were improved. Increase of regional contractile function was directly related to the functionality of the infused cells as measured by their colony-forming capacity. Minimal vascular resistance index was significantly reduced in the BMC-treated vessel after 3 months (from 1.53±0.63 to 1.32±0.61 mm Hg · s/cm; P =0.002, n=24), whereas no changes were observed in the reference vessel (from 1.60±0.45 to 1.49±0.45 mm Hg · s/cm; P =0.133, n=13). Twelve months after BMC infusion, N-terminal prohormone brain natriuretic peptide (NT-proBNP) serum levels were decreased, suggesting a beneficial effect on left ventricular remodeling processes (from 1610±993 to 1473±1147 pg/mL; P =0.038 for logNT-proBNP, n=26). Conclusions— Intracoronary administration of BMC seems to be associated with improvements in cardiac contractile and microvascular function in patients with DCM. Thus, randomized blinded studies are warranted to evaluate potential clinical benefits of intracoronary BMC administration in patients with DCM. Received August 26, 2008; accepted June 24, 2009.Background—Intracoronary administration of bone marrow–derived progenitor cells (BMC) was shown to improve coronary microvascular function in ischemic heart disease. Because coronary microvascular dysfunction is implicated in the pathogenesis and prognosis of nonischemic dilated cardiomyopathy (DCM), we investigated the effects of intracoronary BMC administration in patients with DCM. Methods and Results—Intracoronary infusion of BMC was performed in 33 patients with DCM by using an over-the-wire balloon catheter. Left ventricular contractility at baseline and after 3 months was assessed by analysis of left ventricular angiograms. Coronary hemodynamics were determined by intracoronary Doppler wire measurements. After 3 months, regional wall motion of the target area (contractility from −1.08±0.39 to −0.97±0.47 SD/chord, P=0.029) and global left ventricular ejection fraction (from 30.2±10.9 to 33.4±11.5%, P<0.001) were improved. Increase of regional contractile function was directly related to the functionality of the infused cells as measured by their colony-forming capacity. Minimal vascular resistance index was significantly reduced in the BMC-treated vessel after 3 months (from 1.53±0.63 to 1.32±0.61 mm Hg · s/cm; P=0.002, n=24), whereas no changes were observed in the reference vessel (from 1.60±0.45 to 1.49±0.45 mm Hg · s/cm; P=0.133, n=13). Twelve months after BMC infusion, N-terminal prohormone brain natriuretic peptide (NT-proBNP) serum levels were decreased, suggesting a beneficial effect on left ventricular remodeling processes (from 1610±993 to 1473±1147 pg/mL; P=0.038 for logNT-proBNP, n=26). Conclusions—Intracoronary administration of BMC seems to be associated with improvements in cardiac contractile and microvascular function in patients with DCM. Thus, randomized blinded studies are warranted to evaluate potential clinical benefits of intracoronary BMC administration in patients with DCM.

A Pilot Trial to Assess Potential Effects of Selective Intracoronary Bone Marrow–Derived Progenitor Cell Infusion in Patients With Nonischemic Dilated CardiomyopathyCLINICAL PERSPECTIVE

Background— Intracoronary administration of bone marrow–derived progenitor cells (BMC) was shown to improve coronary microvascular function in ischemic heart disease. Because coronary microvascular dysfunction is implicated in the pathogenesis and prognosis of nonischemic dilated cardiomyopathy (DCM), we investigated the effects of intracoronary BMC administration in patients with DCM. Methods and Results— Intracoronary infusion of BMC was performed in 33 patients with DCM by using an over-the-wire balloon catheter. Left ventricular contractility at baseline and after 3 months was assessed by analysis of left ventricular angiograms. Coronary hemodynamics were determined by intracoronary Doppler wire measurements. After 3 months, regional wall motion of the target area (contractility from −1.08±0.39 to −0.97±0.47 SD/chord, P =0.029) and global left ventricular ejection fraction (from 30.2±10.9 to 33.4±11.5%, P <0.001) were improved. Increase of regional contractile function was directly related to the functionality of the infused cells as measured by their colony-forming capacity. Minimal vascular resistance index was significantly reduced in the BMC-treated vessel after 3 months (from 1.53±0.63 to 1.32±0.61 mm Hg · s/cm; P =0.002, n=24), whereas no changes were observed in the reference vessel (from 1.60±0.45 to 1.49±0.45 mm Hg · s/cm; P =0.133, n=13). Twelve months after BMC infusion, N-terminal prohormone brain natriuretic peptide (NT-proBNP) serum levels were decreased, suggesting a beneficial effect on left ventricular remodeling processes (from 1610±993 to 1473±1147 pg/mL; P =0.038 for logNT-proBNP, n=26). Conclusions— Intracoronary administration of BMC seems to be associated with improvements in cardiac contractile and microvascular function in patients with DCM. Thus, randomized blinded studies are warranted to evaluate potential clinical benefits of intracoronary BMC administration in patients with DCM. Received August 26, 2008; accepted June 24, 2009.Background—Intracoronary administration of bone marrow–derived progenitor cells (BMC) was shown to improve coronary microvascular function in ischemic heart disease. Because coronary microvascular dysfunction is implicated in the pathogenesis and prognosis of nonischemic dilated cardiomyopathy (DCM), we investigated the effects of intracoronary BMC administration in patients with DCM. Methods and Results—Intracoronary infusion of BMC was performed in 33 patients with DCM by using an over-the-wire balloon catheter. Left ventricular contractility at baseline and after 3 months was assessed by analysis of left ventricular angiograms. Coronary hemodynamics were determined by intracoronary Doppler wire measurements. After 3 months, regional wall motion of the target area (contractility from −1.08±0.39 to −0.97±0.47 SD/chord, P=0.029) and global left ventricular ejection fraction (from 30.2±10.9 to 33.4±11.5%, P<0.001) were improved. Increase of regional contractile function was directly related to the functionality of the infused cells as measured by their colony-forming capacity. Minimal vascular resistance index was significantly reduced in the BMC-treated vessel after 3 months (from 1.53±0.63 to 1.32±0.61 mm Hg · s/cm; P=0.002, n=24), whereas no changes were observed in the reference vessel (from 1.60±0.45 to 1.49±0.45 mm Hg · s/cm; P=0.133, n=13). Twelve months after BMC infusion, N-terminal prohormone brain natriuretic peptide (NT-proBNP) serum levels were decreased, suggesting a beneficial effect on left ventricular remodeling processes (from 1610±993 to 1473±1147 pg/mL; P=0.038 for logNT-proBNP, n=26). Conclusions—Intracoronary administration of BMC seems to be associated with improvements in cardiac contractile and microvascular function in patients with DCM. Thus, randomized blinded studies are warranted to evaluate potential clinical benefits of intracoronary BMC administration in patients with DCM.

Elevated Levels of the Mediator of Catabolic Bone Remodeling RANKL in the Bone Marrow Environment Link Chronic Heart Failure with Osteoporosis

Background—Chronic heart failure (CHF) is associated with a 4-fold increased risk for osteoporotic fractures. Therefore, we sought to identify the pathophysiological link between chronic heart failure and catabolic bone remodeling. Methods and Results—In a total cohort of 153 subjects (123 patients with CHF, 30 patients with coronary artery disease and preserved cardiac function) as well as mice with heart failure, bone marrow (BM) plasma levels of the catabolic receptor activator of NF-&kgr;B ligand (RANKL), and its antagonist, osteoprotegerin were measured. The osteoclast inducing activity of BM plasma was tested in cell culture. BM plasma levels of RANKL and of the ratio RANKL/osteoprotegerin were significantly elevated in patients with CHF. On multivariate regression analysis, parameters of severity and duration of heart failure were independent determinants of elevated BM plasma RANKL levels. BM plasma levels of RANKL were directly correlated with the systemic marker of bone turnover C-telopeptide of type 1 collagen (r=0.6; P<0.001). Alterations in BM plasma levels of RANKL/osteoprotegerin were confirmed in a mouse model of postinfarction heart failure. Stimulation of human mesenchymal cells with BM plasma obtained from CHF patients increased the formation of osteoclasts, and this effect was blocked by the RANKL inhibition. Conclusions—CHF is associated with a profound and selective elevation of the bone resorption stimulating RANKL within the BM microenvironment. These data for the first time disclose a direct pathophysiological pathway linking CHF with catabolic bone remodeling associated with an increased osteoporotic fracture risk. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifiers: NCT 00289822, NCT 00284713, NCT 00326989, NCT 00962364.

Procedural Safety and Predictors of Acute Outcome of Intracoronary Administration of Progenitor Cells in 775 Consecutive Procedures Performed for Acute Myocardial Infarction or Chronic Heart Failure

Background—Cell-based therapies are a promising option in patients with acute myocardial infarction or chronic heart failure (CHF). However, administration of cells requires intracoronary or intracardiac instrumentation, which is potentially associated with periprocedural risks. Therefore, we analyzed periprocedural complications and 30-day outcome in 775 consecutive procedures of intracoronary administration of progenitor cells using the stop-flow technique. Methods and Results—Indications for cell administration were acute myocardial infarction (n=126) and CHF of ischemic (n=562) or nonischemic (n=87) etiology. Vessel injury was observed in a total of 9 procedures (1.2%) and could be promptly managed by additional progenitor cell injection (PCI) in all but 1 case. No procedural deaths were observed. A periprocedural increase in troponin T was observed in 3.2% of the CHF procedures, in which no concomitant PCI was performed and troponin levels were not elevated before the procedure. Independent significant predictors of troponin T increase were higher New York Heart Association (NYHA) class (NYHA I versus NYHA IV; P=0.01; NYHA I versus III; P=0.19; NYHA I versus II; P=0.55), concomitant revascularization (P<0.01), presence of elevated troponin T before the procedure (P<0.01), and peripheral occlusive disease (P=0.04). At 30 days, there were 4 deaths (0.5%), 1 stroke (0.13%), 8 acute myocardial infarctions (1%), and 5 hospitalizations for exacerbation of heart failure (0.64%). Conclusions—Intracoronary infusion of progenitor cells can be performed with adequate safety in patients with acute myocardial infarction or CHF, because the safety profile was similar to what is usually expected from a coronary angiogram in the present cohort. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00962364, NCT00284713, and NCT00289822.

MICRA Leadless Pacemaker on Autopsy

Two new leadless pacing systems were recently developed to avoid pocket- and lead-related complications [(1,2)][1]. There is very limited information regarding long-term healing-in of leadless pacemakers [(3)][2]. A 68-year-old man with a history of meningitis, type 2 diabetes mellitus,

A Pilot Trial to Assess Potential Effects of Selective Intracoronary Bone Marrow-Derived Progenitor Cell Infusion in Patients with Non-Ischemic Dilated Cardiomyopathy: Final 1-Year Results of the TOPCARE-DCM Trial

Background— Intracoronary administration of bone marrow–derived progenitor cells (BMC) was shown to improve coronary microvascular function in ischemic heart disease. Because coronary microvascular dysfunction is implicated in the pathogenesis and prognosis of nonischemic dilated cardiomyopathy (DCM), we investigated the effects of intracoronary BMC administration in patients with DCM. Methods and Results— Intracoronary infusion of BMC was performed in 33 patients with DCM by using an over-the-wire balloon catheter. Left ventricular contractility at baseline and after 3 months was assessed by analysis of left ventricular angiograms. Coronary hemodynamics were determined by intracoronary Doppler wire measurements. After 3 months, regional wall motion of the target area (contractility from −1.08±0.39 to −0.97±0.47 SD/chord, P =0.029) and global left ventricular ejection fraction (from 30.2±10.9 to 33.4±11.5%, P <0.001) were improved. Increase of regional contractile function was directly related to the functionality of the infused cells as measured by their colony-forming capacity. Minimal vascular resistance index was significantly reduced in the BMC-treated vessel after 3 months (from 1.53±0.63 to 1.32±0.61 mm Hg · s/cm; P =0.002, n=24), whereas no changes were observed in the reference vessel (from 1.60±0.45 to 1.49±0.45 mm Hg · s/cm; P =0.133, n=13). Twelve months after BMC infusion, N-terminal prohormone brain natriuretic peptide (NT-proBNP) serum levels were decreased, suggesting a beneficial effect on left ventricular remodeling processes (from 1610±993 to 1473±1147 pg/mL; P =0.038 for logNT-proBNP, n=26). Conclusions— Intracoronary administration of BMC seems to be associated with improvements in cardiac contractile and microvascular function in patients with DCM. Thus, randomized blinded studies are warranted to evaluate potential clinical benefits of intracoronary BMC administration in patients with DCM. Received August 26, 2008; accepted June 24, 2009.Background—Intracoronary administration of bone marrow–derived progenitor cells (BMC) was shown to improve coronary microvascular function in ischemic heart disease. Because coronary microvascular dysfunction is implicated in the pathogenesis and prognosis of nonischemic dilated cardiomyopathy (DCM), we investigated the effects of intracoronary BMC administration in patients with DCM. Methods and Results—Intracoronary infusion of BMC was performed in 33 patients with DCM by using an over-the-wire balloon catheter. Left ventricular contractility at baseline and after 3 months was assessed by analysis of left ventricular angiograms. Coronary hemodynamics were determined by intracoronary Doppler wire measurements. After 3 months, regional wall motion of the target area (contractility from −1.08±0.39 to −0.97±0.47 SD/chord, P=0.029) and global left ventricular ejection fraction (from 30.2±10.9 to 33.4±11.5%, P<0.001) were improved. Increase of regional contractile function was directly related to the functionality of the infused cells as measured by their colony-forming capacity. Minimal vascular resistance index was significantly reduced in the BMC-treated vessel after 3 months (from 1.53±0.63 to 1.32±0.61 mm Hg · s/cm; P=0.002, n=24), whereas no changes were observed in the reference vessel (from 1.60±0.45 to 1.49±0.45 mm Hg · s/cm; P=0.133, n=13). Twelve months after BMC infusion, N-terminal prohormone brain natriuretic peptide (NT-proBNP) serum levels were decreased, suggesting a beneficial effect on left ventricular remodeling processes (from 1610±993 to 1473±1147 pg/mL; P=0.038 for logNT-proBNP, n=26). Conclusions—Intracoronary administration of BMC seems to be associated with improvements in cardiac contractile and microvascular function in patients with DCM. Thus, randomized blinded studies are warranted to evaluate potential clinical benefits of intracoronary BMC administration in patients with DCM.

Takotsubo Cardiomyopathy Triggered by Venous Air Embolism During Craniotomy in the Sitting Position

BACKGROUND We present a case of stress-induced cardiomyopathy (Takotsubo cardiomyopathy) caused by a venous air embolism during a craniotomy performed in the sitting position. CASE DESCRIPTION A 69-year-old woman was admitted to the neurosurgical department and scheduled for elective resection of a cerebellar metastasis in the sitting position. After craniotomy and opening of the posterior fossa, a venous air embolism was detected via transesophageal echocardiography. The patient immediately presented with cardiac decompensation with signs of takotsubo or stress-induced cardiomyopathy. CONCLUSIONS Intensivists and anesthesiologists in the operating room and in intensive care units need to be aware of stress-induced cardiomyopathy as a probably underdiagnosed disease entity, especially as management differs significantly from other forms of cardiogenic shock. Diagnosis can be accomplished quickly by bedside echocardiography, emphasizing the need for availability of this tool and the integration of stress-induced cardiomyopathy in diagnostic algorithms in the intensive care unit.

TCT-677 Comparison of surgical versus interventional treatment of aortic valve stenosis in kidney transplant recipients

Surgical aortic valve replacement (SAVR) in kidney transplant recipients (KTR) with severe aortic stenosis (AS) is associated with high morbidity and mortality, especially due to cardiovascular and infectious complications, as well as an increased risk of postoperative kidney failure potentially