Left ventricular assist device for end-stage heart failure: results of the first LVAD destination program in the Netherlands.

PURPOSE: Mechanical circulatory support with a continuous-flow left ventricular assist device (LVAD) may be a valuable treatment in end-stage heart failure patients for an extended period of time. The purpose of this study was to evaluate the safety and efficacy of implantation of a continuous-flow LVAD in end-stage heart failure patients within the first destination program in the Netherlands. METHODS: A third-generation LVAD was implanted in 16 heart failure patients (age 61 ± 8; 81 % male; left ventricular ejection fraction 20 ± 6 %) as destination therapy. All patients were ineligible for heart transplant. At baseline, 3 and 6 months, New York Heart Association (NYHA) functional class, quality-of-life and exercise capacity were assessed. Clinical adverse events were registered. RESULTS: Survival at 30 days and 6 months was 88 and 75 %, respectively. In the postoperative phase, 6 (38 %) patients required continuous veno-venous haemofiltration for renal failure and 2 (13 %) patients required extracorporeal membrane oxygenation because of severe right ventricular failure. During follow-up, NYHA functional class and quality-of-life improved from 3.7 ± 0.1 to 2.3 ± 0.1 and 57 ± 5 to 23 ± 3 at 6 months (P < 0.001), respectively. The 6 min walking distance improved from 168 ± 42 m to 291 ± 29 m at 6 months (P = 0.001). CONCLUSION: Continuous-flow LVAD therapy is a promising treatment for patients with end-stage heart failure ineligible for heart transplant.

Treatment options in end-stage heart failure: where to go from here?

Chronic heart failure is a major healthcare problem associated with high morbidity and mortality. Despite significant progress in treatment strategies, the prognosis of heart failure patients remains poor. The golden standard treatment for heart failure is heart transplantation after failure of medical therapy, surgery and/or cardiac resynchronisation therapy. In order to improve patients' outcome and quality of life, new emerging treatment modalities are currently being investigated, including mechanical cardiac support devices, of which the left ventricular assist device is the most promising treatment option. Structured care for heart failure patients according to the most recent international heart failure guidelines may further contribute to optimal decision-making. This article will review the conventional and novel treatment modalities of heart failure.

Standardised pre-hospital care of acute myocardial infarction patients: MISSION! guidelines applied in practice.

Background. To improve acute myocardial infarction (AMI) care in the region 'Hollands-Midden' (the Netherlands), a standardised guideline-based care program was developed (MISSION!). This study aimed to evaluate the outcome of the pre-hospital part of the MISSION! program and to study potential differences in pre-hospital care between four areas of residency.Methods. Time-to-treatment delays, AMI risk profile, cardiac enzymes, hospital stay, in-hospital mortality, and pre-AMI medication was evaluated in consecutive AMI patients (n=863, 61±13years, 75% male) transferred to the Leiden University Medical Center for primary percutaneous coronary intervention (PCI).Results. Median time interval between onset of symptoms and arrival at the catheterisation laboratory was 150 (interquartile range [IQR] 101-280) minutes. The alert of emergency services to arrival at the hospital time was 48 (IQR 40-60) minutes and the door-to-catheterisation laboratory time was 23 (IQR 13-42) minutes. Despite significant regional differences in ambulance transportation times no difference in total time from onset of symptoms to arrival at the catheterisation room was found. Peak troponin T was 3.33 (IQR 1.23-7.04) µg/l, hospital stay was 2 (IQR 2-3) days and in-hospital mortality was 2.3%. Twelve percent had 0 known risk factors, 30% had one risk factor, 45% two to three risk factors and 13% had four or more risk factors. No significant differences were observed for AMI risk profiles and medication pre-AMI. Conclusions. This study shows that a standardised regional AMI treatment protocol achieved optimal and uniformly distributed pre-hospital performance in the region 'Hollands-Midden', resulting in minimal time delays regardless of area of residence. Hospital stay was short and in-hospital mortality low. Of the patients, 88% had ≥1 modifiable risk factor. (Neth Heart J 2010;18:408-15.).

Single-beat estimation of the left ventricular end-systolic pressure-volume relationship in patients with heart failure.

AIM: The end-systolic pressure-volume relationship (ESPVR) constructed from multiple pressure-volume (PV) loops acquired during load intervention is an established method to asses left ventricular (LV) contractility. We tested the accuracy of simplified single-beat (SB) ESPVR estimation in patients with severe heart failure. METHODS: Nineteen heart failure patients (NYHA III-IV) scheduled for surgical ventricular restoration and/or restrictive mitral annuloplasty and 12 patients with normal LV function scheduled for coronary artery bypass grafting were included. PV signals were obtained before and after cardiac surgery by pressure-conductance catheters and gradual pre-load reductions by vena cava occlusion (VCO). The SB method was applied to the first beat of the VCO run. Accuracy was quantified by the root-mean-square-error (RMSE) between ESPVR(SB) and gold-standard ESPVR(VCO). In addition, we compared slopes (E(ES)) and intercepts (end-systolic volume at multiple pressure levels (70-100 mmHg: ESV(70)-ESV(100)) of ESPVR(SB) vs. ESPVR(VCO) by Bland-Altman analyses. RESULTS: RMSE was 1.7 + or - 1.0 mmHg and was not significantly different between groups and not dependent on end-diastolic volume, indicating equal, high accuracy over a wide volume range. SB-predicted E(ES) had a bias of -0.39 mmHg mL(-1) and limits of agreement (LoA) -2.0 to +1.2 mmHg mL(-1). SB-predicted ESVs at each pressure level showed small bias (range: -10.8 to +9.4 mL) and narrow LoA. Two-way anova indicated that differences between groups were not dependent on the method. CONCLUSION: Our findings, obtained in hearts spanning a wide range of sizes and conditions, support the use of the SB method. This method ultimately facilitates less invasive ESPVR estimation, particularly when coupled with emerging noninvasive techniques to measure LV pressures and volumes.

Guidelines for heart transplantation.

Based on the changes in the field of heart transplantation and the treatment and prognosis of patients with heart failure, these updated guidelines were composed by a committee under the supervision of both the Netherlands Society of Cardiology and the Netherlands Association for Cardiothoracic surgery (NVVC and NVT).THE INDICATION FOR HEART TRANSPLANTATION IS DEFINED AS: 'End-stage heart disease not remediable by more conservative measures'.CONTRAINDICATIONS ARE: irreversible pulmonary hypertension/elevated pulmonary vascular resistance; active systemic infection; active malignancy or history of malignancy with probability of recurrence; inability to comply with complex medical regimen; severe peripheral or cerebrovascular disease and irreversible dysfunction of another organ, including diseases that may limit prognosis after heart transplantation.Considering the difficulties in defining end-stage heart failure, estimating prognosis in the individual patient and the continuing evolution of available therapies, the present criteria are broadly defined. The final acceptance is done by the transplant team which has extensive knowledge of the treatment of patients with advanced heart failure on the one hand and thorough experience with heart transplantation and mechanical circulatory support on the other hand. (Neth Heart J 2008;16:79-87.).

[Infusion of inotropic agents at home in patients with severe heart failure: an important role for the nurse practitioner]. / Thuisinfusie van inotropica bij ernstig hartfalen; een belangrijke rol voor de 'nurse practitioner'.

Patients with severe heart failure commonly require intravenous inotropic agents to stabilise their haemodynamics and improve the clinical symptoms. Continuous intravenous inotropic agents in a home-based setting under the direction of specialised nurses has been introduced in patients waiting for cardiac transplantation and also as destination therapy. Since 1982, several case reports and case series have described the use of ambulatory intravenous dobutamine, but almost none of the available studies included a control group. Moreover, most trials were small and short in duration, and thus have not been able to provide reliable information about the effect of treatment on the risk of serious cardiac events. However, these data consistently demonstrate the feasibility of home infusion as well as an improved quality of life and reduced costs. Therefore, home infusion of dobutamine guided by a specialised nurse may be desirable in patients waiting for heart transplantation or as destination therapy in the last weeks of life.

Different phenotypic expression in relatives with fabry disease caused by a W226X mutation.

Two male relatives with Fabry disease presented striking differences in clinical symptoms and age of onset. The propositus had retarded statural growth and skeletal dysplasia while his nephew suffered mainly from aggravating acroparesthesia and celiac disease. Fabry disease is an X-linked inborn error of glycosphingolipid metabolism resulting from deficient activity of the lysosomal hydrolase alpha-galactosidase A (alpha-Gal A) enzyme. The alpha-Gal A gene is located at Xq22.1. Efforts to establish genotype-phenotype correlations have been limited because most patients have private mutations. In previous clinical studies performed in families with Fabry disease, marked differences in phenotype are described between affected relatives. This family also demonstrates the difficulty in predicting the clinical phenotype in patients and relatives with the same alpha-Gal A mutation. Furthermore, in the absence of a family history, the diagnosis may be easily missed.

Enhanced susceptibility of low-density lipoproteins to oxidation in coronary bypass patients with progression of atheroscerosis.

Oxidation of low-density lipoprotein (LDL) may play a causal role in atherosclerosis. In this study we analyzed whether the severity of progression of coronary atherosclerosis is related to the susceptibility of LDL to oxidative modification. On the basis of repeated coronary angiography, 28 coronary bypass patients were divided into two groups: group A, 12 patients with, and group B, 16 patients without progression of coronary atherosclerosis. The lag time, reflecting the resistance of LDL to oxidative modification, was significantly smaller in group A as compared with group B (81 +/- 10 and 93 +/- 15 min, respectively). Besides differences in cholesterol and apolipoprotein B concentrations, the difference in susceptibility of LDL to oxidation significantly contributes to the differences between the progression and the non-progression group (P = 0.02). In the combined groups of patients, the lag phase of LDL for oxidation was positively correlated with LDL cholesterol ester to protein ratio (r = 0.53, P = 0.01). It is concluded that LDL samples obtained from coronary bypass patients differ with respect to their oxidizability depending on progression of atherosclerosis following coronary bypass surgery.

Too early for cardiac transplantation--the right decision?

In 109 out of 479 patients who were referred for cardiac transplantation it was considered to be too early to put them on the waiting list for a donor heart. The clinical course of these 109 patients was analysed in order to verify whether this decision had been right. The mean age of the patients was 43 years, half of them suffered from ischaemic heart disease. The systolic left ventricular function of the patients was severely depressed (mean left ventricular ejection fraction 21%) and the left ventricular cavity was markedly dilated (mean echocardiographic end diastolic dimension 73 mm). Functional capacity, measured by bicycle ergometry, was low: mean maximal workload 62% of the expected load for gender, height and age. The median follow-up duration was 31 months. The survival rate of the patients was better than that of 175 patients who were accepted for transplantation after referral, 92%, 87%, 81%, 71% and 73%, 73%, 71%, 68% after 1, 2, 3 and 4 years respectively. Re-assessment was necessary in 29% of the patients within 1 year and in 52% within 3 years. Twenty patients died: 12 patients died before re-assessment had been initiated (eight sudden deaths), six patients because of progressive heart failure before heart transplantation could be performed and two patients died after heart transplantation. Left ventricular ejection fraction, pulmonary capillary wedge pressure and transpulmonary gradient were not reliable predictors of the course of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Is diltiazem effective in treating the symptoms of (tardive) dyskinesia in chronic psychiatric inpatients? A negative, double-blind, placebo-controlled trial.

Calcium channel blockers, antiarrhythmic drugs, such as verapamil and diltiazem, may decrease the symptoms of tardive dyskinesia. The efficacy and safety of administering 60 mg diltiazem hydrochloride, four times daily for a period of 3 weeks, was studied in a random, double-blind, crossover trial in which the drug was compared with placebo in 17 neuroleptic-treated, chronic psychiatric inpatients of both genders with (tardive) dyskinesia. The severity of the dyskinesia was assessed using the Abnormal Involuntary Movement Scale. Neither diltiazem nor placebo produced a significant decrease in the severity of the dyskinesia. Diltiazem did not influence the psychiatric state of the patients, nor did it have a significant effect on either the blood pressure or electrocardiographic parameters. No significant adverse drug reactions were elicited.

MR imaging in assessment of cardiac transplant rejection in humans.

To evaluate the efficacy of myocardial T2 values in the assessment of allograft rejection, we performed magnetic resonance (MR) imaging at 0.5 T serially in seven cardiac transplant recipients and singly in seven normal volunteers. Cardiac-gated multi-echo spin echo images were obtained; T2 values were estimated by a two-point method from regions of interest in the myocardium. Patients underwent MR and cardiac biopsy at various times after transplantation. Forty-two patient exams were performed. All biopsies showed either no rejection or early stages of rejection: grade 0 in 8 examinations, grade 1 in 28, and grade 2 in 6. Myocardial T2 values in patients in early stages of cardiac rejection were slightly higher (but not statistically significant) than those in non-rejecting patients and normal volunteers. Although this study did not allow prospective detection of cardiac rejection in our patient group, it demonstrated a trend toward higher T2 values at higher biopsy grades that may indicate an ability to assess more severe stages of transplant rejection.

Retrospective analysis of drug treatment in epileptic patients.

An epidemiological analysis was performed of the adult, out-patient epilepsy clinic population of a university hospital during the period from 1 January 1981 through 30 June 1985. The number of patients that could be traced amounted to 590. An at random sample of 207 were retrospectively analysed. Gender distribution was male:female = 1.46. The mean age was 37.4 years. The diagnoses were classified according to the classification of the International League Against Epilepsy (ILAE). A preponderance of partial seizures was present, reflecting the selection in a university out-patient clinic of more difficult to treat forms of epilepsy. Antiepileptic drugs used in the treatment varied; monotherapy was obtained in 46% of the cases and carbamazepine was the most frequently prescribed drug (49%). Changes in seizure severity and factors associated with epilepsy are described. A discrepancy was found between the suspected drug levels, based upon the physician's judgement, and the plasma level measured in those patients in whom drug levels were monitored; factors interfering with clinical judgement are discussed.

Microcomputer-based system for 24-hour recording of oesophageal motility and pH profile with automated analysis.

A system developed for long-term simultaneous recording of oesophageal motility and pH in the ambulant patient is described. The system consists of a microprocessor based data-acquisition and preprocessing device, a personal computer for postprocessing, report generation and data storage, a miniature two-sensor pressure catheter and a pH electrode. Identification and classification of oesophageal contractions are performed in separate steps, using online preprocessing software for identification and offline postprocessing software for categorisation, classification and report generation. Contractions are categorised as peristaltic, simultaneous or nontransmitte and classified according to their amplitude, duration and propagation velocity. The method described reduces the amount of data from 870 kbyte to approximately 40 kbyte per 24 hours in a multiparameter recording device, and offers the opportunity for offline postprocessing with different sets of criteria. The system has been found to be accurate and reliable in 24-hour studies in both healthy volunteers and patients with non-cardiac chest pain.