Peter Bo Hansen

Incidence of ventricular arrhythmias in patients on long-term support with a continuous-flow assist device (HeartMate II).

The incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients supported with a continuous-flow left ventricular assist device (LVAD) has not been investigated in detail. In 23 consecutive recipients of a HeartMate II, we analyzed the incidence of VT/VF during a total of 266 months of follow-up. Sustained VT or VF occurred in 52% of the patients, with the majority of arrhythmias occurring in the first 4 weeks after LVAD implantation. VT/VF requiring implantable cardioverter-defibrillator (ICD) shock or external defibrillation occurred in 8 patients and significant hemodynamic instability ensued in 3 patients. There were no clear predictors of VT/VF, and it is argued that prophylactic ICD implantation should be considered in patients supported with a continuous-flow LVAD.

Central and Peripheral Blood Flow During Exercise With a Continuous-Flow Left Ventricular Assist DeviceClinical Perspective

Background— End-stage heart failure is associated with impaired cardiac output (CO) and organ blood flow. We determined whether CO and peripheral perfusion are maintained during exercise in patients with an axial-flow left ventricular assist device (LVAD) and whether an increase in LVAD pump speed with work rate would increase organ blood flow. Methods and Results— Invasively determined CO and leg blood flow and Doppler-determined cerebral perfusion were measured during 2 incremental cycle exercise tests on the same day in 8 patients provided with a HeartMate II LVAD. In random order, patients exercised both with a constant (≈9775 rpm) and with an increasing pump speed (+400 rpm per exercise stage). At 60 W, the elevation in CO was more pronounced with increased pump speed (8.7±0.6 versus 8.1±1.1 L · min−1; mean±SD; P=0.05), but at maximal exercise increases in CO (from 7.0±0.9 to 13.6±2.5 L · min−1; P<0.01) and leg blood flow [0.7 (0.5 to 0.8) to 4.4 (3.9 to 4.8) L · min−1 per leg; median (range); P<0.001] were similar with both pumping modes. Normally, middle cerebral artery mean flow velocity increases from ≈50 to ≈65 cm · s−1 during exercise, but in LVAD patients with a constant pump speed it was low at rest (39±14 cm · s−1) and remained unchanged during exercise, whereas in patients with increasing pump speed, it increased by 5.2±2.8 cm · s−1 at 60 W (P<0.01). Conclusions— With maximal exercise, the axial-flow LVAD supports near-normal increments in cardiac output and leg perfusion, but cerebral perfusion is poor. Increased pump speed augments cerebral perfusion during exercise.

Reduction of digoxin-induced inotropism during quinidine administration

A kinetic and dynamic study of digoxin was performed in 6 healthy subjects, and repeated in the same subjects after administration of quinidine for 1 wk. Myocardial performance evaluated by systolic time intervals increased in parallel with plasma digoxin concentration, whereas left ventricular end‐diastolic diameter on echocardiography and arterial blood pressure remained constant. The positive inotropic effect of digoxin was abolished during concomitant treatment with quinidine. Quinidine has been reported to increase the risk of digitoxicity, and therefore the treatment with digoxin and quinidine in combination should be reconsidered.

Amiloride‐induced changes in digoxin dynamics and kinetics: Abolition of digoxin‐induced inotropism with amiloride

Digoxin dynamics and kinetics were studied in six healthy subjects with and without amiloride. Amiloride increased mean renal digoxin clearance from 1.3 to 2.4 ml · kg−1 · min−1 (p < 0.001) due to increased tubular secretion of digoxin, while the glomerular filtration rate was unchanged. This might be caused by an increase in intracellular potassium concentration in the tubular cells provoked by amiloride. In contrast, the extrarenal clearance of digoxin was almost blocked by amiloride; it fell from a mean of 2.1 to 0.2 ml · kg−1 · min −1 (p < 0.025). Total body clearance tended to fall, but the decrease was not statistically significant. Evaluation of myocardial contractility by systolic time intervals revealed a concentration‐response relationship between digoxin and changes in preejection period index when digoxin was given alone (rs = 0.750, p < 0.001). Pretreatment with amiloride abolished this relationship (rs = 0.307, p = NS). Blood pressure and echocardiographically determined left ventricular end‐diastolic diameter measurements indicated no changes in the left ventricular post‐ and preload. It is concluded that amiloride suppressed digoxin‐induced inotropism.

Central and Peripheral Blood Flow During Exercise With a Continuous-Flow Left Ventricular Assist Device Constant Versus Increasing Pump Speed: A Pilot Study

Background— End-stage heart failure is associated with impaired cardiac output (CO) and organ blood flow. We determined whether CO and peripheral perfusion are maintained during exercise in patients with an axial-flow left ventricular assist device (LVAD) and whether an increase in LVAD pump speed with work rate would increase organ blood flow. Methods and Results— Invasively determined CO and leg blood flow and Doppler-determined cerebral perfusion were measured during 2 incremental cycle exercise tests on the same day in 8 patients provided with a HeartMate II LVAD. In random order, patients exercised both with a constant (≈9775 rpm) and with an increasing pump speed (+400 rpm per exercise stage). At 60 W, the elevation in CO was more pronounced with increased pump speed (8.7±0.6 versus 8.1±1.1 L · min−1; mean±SD; P=0.05), but at maximal exercise increases in CO (from 7.0±0.9 to 13.6±2.5 L · min−1; P<0.01) and leg blood flow [0.7 (0.5 to 0.8) to 4.4 (3.9 to 4.8) L · min−1 per leg; median (range); P<0.001] were similar with both pumping modes. Normally, middle cerebral artery mean flow velocity increases from ≈50 to ≈65 cm · s−1 during exercise, but in LVAD patients with a constant pump speed it was low at rest (39±14 cm · s−1) and remained unchanged during exercise, whereas in patients with increasing pump speed, it increased by 5.2±2.8 cm · s−1 at 60 W (P<0.01). Conclusions— With maximal exercise, the axial-flow LVAD supports near-normal increments in cardiac output and leg perfusion, but cerebral perfusion is poor. Increased pump speed augments cerebral perfusion during exercise.

Interactions between digoxin and potassium‐sparing diuretics

A kinetic and hemodynamic study of digoxin was performed in six healthy subjects and similar studies were performed during digoxin with spironolactone and with triamterene. Spironolactone reduced renal tubular secretion of digoxin and attenuated its positive inotropic effect (evaluated by systolic time intervals and echocardiography) and triamterene reduced the extrarenal elimination of digoxin, but induced no changes in digoxin‐elicited inotrophy. It is suggested that the renal handling of digoxin is influenced by the intracellular potassium concentration in the renal tubular cell. The results indicate a drug‐receptor interaction between spironolactone metabolites and digoxin at the hypothetical inotropic digitalis receptor. Amiloride has been reported to suppress digoxin inotropism, whereas spironolactone induces minor inhibition and triamterene does not affect digoxin inotropism.

First-in-Human Case of Transfemoral CardiAQ Mitral Valve Implantation

Major advancements have been made in transcatheter aortic and pulmonary valve implantation during the past decade. However, transcatheter mitral valve implantation (TMVI) poses different challenges because of the complexity of the mitral valve apparatus. Although several companies are attempting to develop transcatheter approaches for mitral valve repair, these technologies may have limited applicability because of the heterogeneous nature of the disease and, to date, this strategy has had a difficult time demonstrating the efficacy that is equivalent to surgical approaches. In this report, we describe the first-in-human percutaneous transfemoral-TMVI, which was performed at Rigshospitalet in Copenhagen, Denmark on June 12, 2012 using a dedicated device.nnAn 86-year-old male with symptomatic mitral regurgitation (MR) was referred for interventional treatment. Transesophageal echocardiography showed severe MR (grade, 3+ to 4) because of mitral annular dilatation and a severely restricted posterior mitral leaflet in a dilated left ventricle (LV) with ejection fraction 40%. The patient was declined for mitral valve surgery (Society of Thoracic Surgeons score, 31.9%) and for MitraClip treatment because of a too large systolic coaptation gap. An informed consent from the patient and approval from the Danish National Board of Health were obtained for this first-in-human TMVI procedure using the first-generation CardiAQ valve (CardiAQ Valve Technologies, Irvine, CA; Figure 1).nnnnFigure 1. nCardiAQ prosthesis consists of a self-expanding nitinol frame, which has 3 leaflets of bovine pericardial tissue and is covered with a polytetrafluoroethylene membrane to minimize paravalvular leakage. The frame design features 2 sets of opposing left ventricular anchors and allows for annular attachment without radial force. The frame engages and preserves the native subvalvular apparatus and features a 40-mm anchoring region and a 30-mm inflow region. A , First-generation device, as used in the first-in-human transfemoral CardiAQ case. B , Second-generation device, which offers improved load distribution, optimized flow properties …

Long-term outcome in patients treated with combined heart and liver transplantation for familial amyloidotic cardiomyopathy.

The amyloidogenic transthyretin (ATTR) mutation Leu111Met causes a primarily cardiac amyloidosis: Familial amyloidotic cardiomyopathy (FAC). Combined heart–liver transplantation (CHLTx) is the preferred treatment for patients with heart failure due to familial amyloidosis, but information on outcome of patients with Leu111Met mutation is limited. The aim of this study was to evaluate the long‐term outcome of CHLTx in patients with FAC.

Driveline infections in patients supported with a HeartMate II: Incidence, aetiology and outcome

Abstract Objectives. To investigate the incidence and outcome of driveline infections in patients supported with a continuous flow left ventricular assist device (HeartMate II (HMII)) and to study the microbiological aetiology. Design. Retrospective analysis of 31 patients who received an implantation of a HMII. Follow-up was from implantation to either device explantation, death or closure of the study. Clinical signs of infections were divided into superficial, deep or systemic and compared to culture and gram stain, the clinical course and infectious parameters. Results. The incidence of driveline infections was 1.65 episodes per patient per year. Staphylococcus aureus and Escherichia coli were the most common bacterial aetiology. More than two weeks of treatment was required in 81% of the patients. In terms of detecting superficial driveline infections, leucocyte count demonstrated a sensitivity of 27% and C-reactive protein (CRP) a sensitivity of 28%. In 22 cases of driveline infections plasma pro-calcitonin was found to be normal. Conclusion. Driveline infections are common in HMII recipients but primarily remain superficial and are reasonably easy to manage. Infectious agents mostly originate from the skin and gastrointestinal tract. Blood biomarkers did not appear to be helpful in detecting driveline infections.

Renal digoxin clearance: Dependence on plasma digoxin and diuresis

SummaryThe renal handling of digoxin in animals involves glomerular filtration, tubular secretion and tubular reabsorption, while only glomerular filtration and tubular secretion have been described in humans. The influence of plasma digoxin and urine flow on the renal handling of digoxin was investigated in 6 healthy volunteers. Non-glomerular renal excretion of digoxin (tubular secretion minus tubular reabsorption) was inversely correlated with plasma digoxin concentration and directly with urine flow. Hence, the present study demonstrated the occurrence of tubular reabsorption in addition to glomerular filtration and tubular secretion of digoxin. The results suggest that renal clearance of digoxin should be increased by increased urine flow, which might be of importance during digoxin toxicity.