The microcirculation in the pathogenesis of organ failure in patients with acute heart failure.

Microcirculation is the part of the circulation where nutrients, water, gases,
hormones, and waste products are exchanged between the blood and cells. The
microcirculation consists of a network of blood vessels less than 100 µm in
diameter (arterioles, capillaries and venules, respectively). An adequate blood
flow within these microvessels is a prerequisite for normal organ perfusion.
The microcirculation also functions as a volume reservoir for blood, so that
the microcirculation plays an important role in regulating preload and cardiac
output of the heart. Another major function of the microcirculation is to
regulate vascular resistance to maintain an adequate arterial pressure.
Regulation of vascular resistance to preserve the arterial pressure (by
constriction of the resistance vessels) and allowing each tissue to receive
sufficient blood flow to sustain metabolism are sometimes in conflict. Often
the temporary compromise is to preserve the mean arterial pressure by
increasing arterial resistance at the expense of reduced blood flow to most
organs; ultimately, however, the tissue exchange function must be restored. In
patients with circulatory failure ("shock"), blood flow is diverted from the
less important tissues (skin, subcutaneous, muscle, gastrointestinal tract) to
vital organs (heart, brain, kidneys). Multiple organ failure is common in these
patients, often despite correction of the alterations in, for example, heart
rate, arterial blood pressure and cardiac output. It is believed that
redistribution of blood flow away from the splanchnic area may result in
translocation of microorganisms from the gut into the blood and that may be one
of the factors contributing to the development of multiple organ failure.
Micro-circulatory blood flow alterations may play an important role in this
process.
Acute heart failure is classified into several clinical conditions. One of the
most threatening is cardiogenic shock. The European Society of Cardiology (ESC)
defines cardiogenic shock as evidence of tissue hypoperfusion induced by heart
failure after correction of preload. There is no clear definition for
hemodynamic parameters, but cardiogenic shock is usually characterized by
reduced blood pressure (mean arterial pressure <65 mmHg), a pulse rate >60
beats per min., cardiac output <2.2 l/min/m2 and low urine output (<0.5
ml/kg/hr). The most common cause of cardiogenic shock is a large acute
myocardial infarction. Mortality of patients with cardiogenic shock remains
high despite agressive revascularization procedures and modern hemodynamic and
respiratory support. Many of these patients experience either fatal arrhythmias
or die with a low cardiac index ("pump failure"). Furthermore, a substantial
number of patients with cardiogenic shock die with a normalized cardiac index
("normalized" with inotropes and/or an intra-aortic balloon pump). We
hypothesize that within these latter patients local microcirculatory blood flow
alterations play an important role in a process that finally leads to death.

We want to prove in at least 100 patients admitted with acute heart failure
that:
1. Microcirculatory blood flow alterations exist in the early course of disease
(i.e. preferably measured before the start of treatment).
2. SDF imaging is a useful bedside tool to evaluate the time course of
microvascular alterations.
3. There is a correlation between microcirculatory alterations and the degree
of organ failure.
4. Microcirculatory perfusion can be changed by common treatment strategies.

The final objective of the study is to investigate whether that the
microcirculation might be a new therapeutic target in patients with severe
heart failure and cardiogenic shock. The knowledge obtained from this pilot
project will result in the start of future trials, which should investigate
whether improvement of microcirculatory flow will have an effect on outcome.

An observational study will be performed at the Intensive Care Unit of the
Thoraxcenter of the Erasmus University Medical Center Rotterdam.

The study will be observational. SDF imaging is a noninvasive method and
recording of SDF sequences can be obtained within a few minutes. Collection of
the other parameters will be based on routine measurements as much as possible.