Implantable devices in heart failure : studies on biventricular pacing and continuous hemodynamic monitoring

Chronic heart failure is a highly symptomatic syndrome associated with increasing prevalence, frequent hospital admissions and high treatment costs. Despite recent advances in drug therapy, morbidity and mortality are still high. Thus, there is a clear need for additional therapeutic options and better diagnostic tools in order to improve the management of patients with heart failure. This thesis investigated two novel device techniques for the treatment and management of patients with chronic heart failure.

Biventricular pacing: Approximately 30% of patients with heart failure have wide QRS complexes on the surface ECG as a sign of disturbed intraventricular conduction. This leads to asynchronous ventricular contraction and relaxation with impaired systolic and diastolic function and increased mitral regurgitation. Biventricular pacing aims to resynchronize the ventricular activation by simultaneous stimulation of the right and left ventricle.

Study I evaluated effects of this therapy on functional status and quality of life (QoL) in 16 patients with NYHA III-IV heart failure. After 6 months of biventricular pacing, NYHA-class, the 6-minute walking distance and QoL had improved significantly. This clinical improvement translated into a marked decrease in the need for hospital care the year after pacemaker implantation.

Study II, a European multicenter study, confirmed these findings in 75 NYHA III heart failure patients. The clinical benefits of biventricular pacing were sustained over 12 months of treatment both in patients with sinus rhythm and atria] fibrillation. In addition, an improvement in left ventricular ejection fraction and a reduction in mitral regurgitation was observed.

Study III investigated the effects of a 2-week treatment cessation of long term biventricular pacing. Myocardial blood flow (MBF) and oxygen consumption (MV02) was assessed by 11-C-acetate positron emission tomography at rest and during low dose dobutamine stress in 6 responders to biventricular pacing. Although MBF was unchanged by biventricular pacing there was significant less increase of MV02 during stress, when the pacemaker had been switched off for 2 weeks.

Continuous hemodynamic monitoring: An implantable hemodynamic monitor (IHM) continuously records central hemodynamic information from a pressure lead in the right ventricle. The system is implanted similar to a pacemaker. In study IV, 32 heart failure patients with an IHM were followed during 9 months. Retrospective analysis of hemodynamic trends showed significant (>20%) pressure changes in 9/12 cases of volume overload exacerbation requiring in-hospital treatment. These changes occurred 4±2 days prior to the clinical event. Hospitalizations decreased when the hemodynamic information was used for clinical decision making.

Study V evaluated the potential usefulness of the IHM for the optimization of diuretic treatment in 4 patients with stable heart failure. Diuretics were decreased by 50% during the first week, completely withdrawn during the second and reinstituted in the initial dose during the third. In parallel with other clinical measures, the IHM was a sensible tool for detecting changes in volume load and was useful to find the optimal diuretic dose.

In study VI an IHM was used to investigate the relationship between N-terminal pro brain natriuretic peptide (NTproBNP) and cardiac filling pressures. NT-proBNP plasma. levels measured on a single occasion varied largely between patients and were only weakly correlated with filling pressures. However, serial measurements of NT-proBNP in the same individual correlated significantly to hemodynamic parameters and reflected individual changes in cardiac filling pressures over time.

Conclusions: Biventricular pacing improves symptoms and exercise tolerance in patients with heart failure and intraventricular conduction delay and favorably impacts the need for hospitalizations. Clinical improvement is sustained over 12 months follow-up and may in part depend on changes in myocardial oxygen metabolism. Continuous hemodynamic monitoring is potentially useful to indicate impending volume exacerbations and to tailor diuretic therapy, which may prevent hospitalizations for heart failure. Serial measurements of NT-proBNP are correlated with hemodynamic changes in the individual patient and may be useful to guide outpatient treatment. In the future, a hemodynamic sensor may be incorporated in pacemakers or defibrillators implanted in patients with heart failure, serving as an integrated heart failure management device.

List of scientific papers

I. Braunschweig F, Linde C, Gadler F, Ryden L (2000). Reduction of hospital days by biventricular pacing. Eur J Heart Fail. 2(4): 399-406.
https://pubmed.ncbi.nlm.nih.gov/11113717

II. Linde C, Leclercq C, Rex S, Garrigue S, Lavergne T, Cazeau S, McKenna W, Fitzgerald M, Deharo JC, Alonso C, Walker S, Braunschweig F, Bailleul C, Daubert JC (2002). Long-term benefits of biventricular pacing in congestive heart failure: results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study. J Am Coll Cardiol. 40(1): 111-8.
https://pubmed.ncbi.nlm.nih.gov/12103264

III. Braunschweig F, Sorensen J, von Bibra H, Olsson A, Ryden L, Langstrom B, Linde C (2002). Effects of biventricular pacing on myocardial blood flow and oxygen consumption in patients with heart failure. A study using carbon-11 acetate positron emission tomography. [Submitted]

IV. Adamson PB, Magalski A, Braunschweig F, Bohm M, Reynolds D, Stenius D, Luby A, Linde C, Ryden L, Stablein A, Takle T, Bennet T (2002). Chronic right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system. [Submitted]

V. Braunschweig F, Linde C, Eriksson MJ, Hofman-Bang C, Ryden L (2002). Continuous haemodynamic monitoring during withdrawal of diuretics in patients with congestive heart failure. Eur Heart J. 23(1): 59-69.
https://pubmed.ncbi.nlm.nih.gov/11741363

VI. Braunschweig F, Fahrleitner A, Manghiavacci M, Ghio S, Fotuhi P, Hoppe UC, Linde C (2002). Serial measurements of N-terminal pro brain natriuretic peptide correlate to ambulatory cardiac filling pressures in outpatients with chronic heart failure. [Manuscript]