This invention relates to a method of haemodynamic assessment of a patient and in particular to the assessment of patients undergoing major surgery, those with suspected cardiac dysfunction or with a mechanical circulatory support devices and for donor heart selection.

The circulatory system of a mammal consists of two pumps (left and right ventricles) and two vessel systems or resistances (systemic and pulmonary) in series. The outputs of the pumps and vessels must be the same for equilibrium to be maintained. Blood flow, volume and pressure are interactive and analysis of all these elements is required for an adequate interpretation of cardiovascular function. In order to characterise the circulatory system it is thus necessary to make measurements in at least two different points.

US 5,103,828 teaches a method and apparatus for the non-invasive diagnosis and therapeutic management of patients having systemic hypertension or other critical illnesses. The disclosure is directed mainly towards non-invasive measurement of the function of the left ventricle of a patient. In patients with good blood pressure (e.g. systemic hypertension) the difference between mean arterial pressure and pressure drop across the systemic circulation will be very small. In critically ill patients mean arterial pressure may be low, whereas the atrial pressure may be high and the use of the mean arterial pressure is not a suitable indication of the cardiovascular function. US 5,103,828 teaches the use of mean arterial pressure is thus unsuitable for use in a critical care environ, for example patients with Cardiogenic shock do not respond in the normal way to treatment, especially if cardiac output is low. There is thus a need for accurate objective data on the left and right ventricular function of an individual patient or donor.

According to a first aspect of the invention there is provided a method for the haemodynamic assessment of a patient comprising: providing coordinate axes for a graphical display of at least a selected one of the left or right ventricular functions with said axes respectively representing pressure drop and cardiac output of the relevant function; distinctively establishing in said display a target area representing normal ranges of coordinate values according to the individual patients parameters; and plotting in said display coordinate values for said patient. According to a second aspect of the invention there is provided apparatus for the haemodynamic assessment of a patient comprising: a graphical display means; means for selecting at least one of the left or right ventricular functions; said graphical display means having coordinate axes respectively representing pressure drop and cardiac output of the relevant function; said graphical display means also having means to establish a target area representing normal ranges according to the individual patients parameters; plotting means for Indicating on the graphical display means the coordinate values for said patient.

Using previously established minimal criteria for each patient 1t 1s possible to delineate a target area of optimum cardiac function. The invention provides a method by which both left and right ventricle pressure drops and cardiac output may be measured and data from such measurements may be used in calculating the ventricular functions of a patient. The disparity between a function at a point in time and the optimum function may be indicated, allowing the patient's response to clinical intervention over a period of time to be analysed and recorded.

The target area may be essentially polygonal and bounded by preselected ranges of pressure drop, cardiac output, resistance and cardiac power. The target area may be related to the patients size by adjusting the minimum criteria according to the individual patients parameters, e.g. with reference to body surface area and condition of the patient. The graphical display may display a nomogram of the left ventricular function, or a nomogram of the right ventricular function or two nomograms showing both left and right functions. The graphical display means may be a printer or a visual display unit (VDU).

The apparatus may include means for measuring the cardiac output, the systemic arterial pressure, right atrial pressure and means for calculating from the measured values the left ventricular function coordinate values for said patient. The apparatus may include means for measuring the cardiac output, the pulmonary arterial pressure and left atrial pressure and means for calculating from the measured values the right ventricular function coordinate values for said patient.

According to a third aspect of the invention there is provided a method for recording the haemodynamic state of a patient comprising: providing coordinate axes for a graphical display of at least one of the left or right ventricular functions with said axes respectively representing pressure drop and cardiac output of the relevant function; distinctively establishing in said display a target area representing normal ranges of coordinate values according to the individual patients parameters; and determining the coordinate values for said patient at a point in time plotting 1n said display coordinate values. According to a fourth aspect of the invention there is provided apparatus for recording the haemodynamic state of a patient comprising; a graphical display means ;

said graphical display means including coordinate axes respectively representing pressure drop and cardiac output of at least one of the left or right ventricular function; said graphical display means also having means to establish a target area representing normal ranges according to the individual patients parameters; means for determining the coordinate values for said patient at a point in time. plotting means for indicating on the graphical display means the coordinate values.

Embodiments of the invention will now be described with reference to the accompanying drawings using suggested minimum criteria and suggested normal ranges, in which:

Figure 1 is a diagram of a display showing minimum criteria of cardiac output and pressure drop across the systemic circulation,

Figure 2 is a diagram of a display showing normal ranges of constant systemic vascular resistance,

Figure 3 is a diagram of a display showing normal ranges of constant power output for the left ventricle,

Figure 4 Is a diagram of a display showing a target area representing normal ranges for the left ventricular function,

Figure 5 is a diagram of a display showing minimum criteria of cardiac output for the right ventricle, Figure 6 is a diagram of a display showing normal ranges of constant pulmonary vascular resistance,

Figure 7 is a diagram of a display showing normal ranges of constant power output for the right ventricle,

Figure 8 is a diagram of a display showing a target area representing normal ranges for the right ventricular function, Figure 9 is diagram of apparatus embodying the invention, Figure 10 illustrates the effects of particular interventions, Figures 11 to 14 illustrate examples 1 to 4.

The selection of minimum criteria will be appreciated by one skilled in the art to be dependent on the individual patient and list of suitable references from which the minimum criteria used in the following examples are selected are given at the end of the description. These minimum criteria are given as a guide to indicate the target area for an aseptic patient (such as a donor heart suitable for transplantation) at rest and other minimum criteria may be used for other patients (such as a patient in septic shock). Figures 1 to 4 illustrates the left ventricular function for a patient with a body surface area of 1.8 ² and show a target haemodynamic area for a patient with that body size. The pressure drop across the systemic circulation, calculated as the mean arterial pressure (AoP) minus the right atrial pressure (RAP), is plotted on the ordinate against cardiac output (CO) on the abscissa. In figure 1 a minimum value for the pressure drop across the systemic circulation of 48 mmHg. calculated from a previously determined minimum mean AoP of 60 mmHg and a maximum RAP of 12 mmHg, 1s Indicated by horizontal line 10. A minimum value of 3.8 1/mln (a cardiac Index of 2.1 1/min, suggested from previous mortality studies of Cardiogenic shock, multiplied by 1.8 m ² ) for the cardiac output is indicated by line 11. The shaded area 12 indicates the preferred state.

Figure 2 shows, plotted on the same axes as figure 1, lines indicating points of constant systemic vascular resistance (SVR), calculated from

SVR = AoP - RAP x 79.9 dynes.s.cm ^-5 CO Line 13 indicates a minimum constant SVR of 800 dynes.s.cm ^-5 and line 14 Indicates a maximum constant SVR of 1200 dynes.s.cm" ⁵ and the shaded area 15 indicates the preferred state.

Figure 3 shows lines, plotted on the same axes as figure 1, lines indicating points of constant mean left ventricular power (LVPo), calculated from

LVPo = (AoP - RAP) x CO x 2.2167 x 0.001 Watts The above mentioned criteria (AoP = 60 mmHg, RAP ^• = 12 mmHg and CO = 3.8 1/min) give a minimum constant LVPo of 0.4 Watts, line 16. A maximum constant LVPo of 1.0 Watt, suggested as the maximum for an aseptic patient at rest, is shown by line 17 and the shaded area 18 indicates the preferred area.

The nomogram of figure 4 is a combination of figures 1 to 3 and the shaded area 19 indicates the target area for the left ventricular function for a patient with a body size of 1.8 m ² , at rest.

Figures 5 to 8 illustrate the right ventricular function for a patient with a body surface area of 1.8 ² and show a target haemodynamic area for a patient with that body size. The pulmonary pressure drop, calculated as the Pulmonary artery pressure (PAP) minus the left atrial pressure (LAP), is plotted on the ordinate against cardiac output (CO) on the abscissa.

In figure 5 the previously determined minimum value of 3.8 1/min for the cardiac output is indicated by line 30. The resistance and therefore the pressure drop across normal lungs should be as low as possible and therefore no minimum criteria needs to be defined. The shaded area 31 indicates the preferred state.

Figure 6 shows, plotted on the same axis as figure 5, lines indicating points of constant pulmonary vascular resistance (PVR), calculated from

PVR •= PAP - LAP x 79.9 dynes.s.cm ^-5 CO Line 32 indicates a maximum constant PVR of 200 dynes.s.cm ^-5 and the shaded area 33 indicates the preferred state. Above such a value, the right ventricle may struggle to support the circulation.

Figure 7 shows lines, plotted on the same axes as figure 5, lines Indicating points of constant mean right ventricular power (RVPo), calculated from

RVPo = (PAP - LAP) x CO x 2.2167 x 0.001 Watts The minimum constant RVPo (at rest), calculated from an estimated minimum pressure drop of 1 mmHg across the lungs, is 0.01 Watts and is shown by line 34. The maximum constant RVPo (at rest), calculated from an estimated maximum pressure drop of 15 mmHg across the lungs, is 0.125 Watts and is shown by line 35. The shaded area 36 indicates the preferred area.

Figure 8 1s a combination of figures 5 to 7 and the shaded area 37 Indicates the target area for the right ventricular function for a patient with a body size of 1.8 m ² , at rest.

The arterial pressure can be monitored invasively or non-invas1vely. In critically ill patients, with or without cardiac dysfunction, the blood pressure is commonly measured invasively. The pulmonary artery pressure (PAP), right atrial pressure (RAP) and left atrial pressure (LAP) are most commonly monitored with a pulmonary artery flotation catheter (i.e. Swan-Ganz catheter). This catheter has two lumens for pressure monitoring and a small balloon near the tip. The catheter is inserted into the Internal jugular vein and the balloon is inflated. The balloon carries the tip of the catheter through the right atrium and ventricle of the right heart and into the pulmonary artery where the balloon becomes wedged. With the balloon deflated the pressure monitoring from the tip measures the PAP. The radial port of the catheter 1s situated in the right atrium and measures RAP. With the balloon inflated one branch of the pulmonary artery is obstructed and therefore the pressure measured at the tip of the catheter, which is in the pulmonary capillaries, is the pulmonary capillary wedge pressure (PCWP) This pressure has been shown in the literature to be closely related to the LAP and may be used in place of the LAP. PAP and LAP may alternatively be measured by monitoring lines left in situ after surgery. A venous catheter in situ may be used to measure the central venous pressure, which is closely related to the RAP and may alternatively be used in place of the RAP. Cardiac output can be measured either invasively , using

the pulmonary artery flotation device as described above by thermal dilution, thermal conductivity, Doppler, ultrasound and other techniques being explored, or non-invasively. Alternatively, during surgery these techniques or others may be used on a directly exposed heart.

Figure 9 shows apparatus including a central processing unit 50 for processing the data collected from the patient 51. The cardiac output (CO), the right atrial pressure (RAP), the pulmonary arterial pressure (PAP) and the left arterial pressure (LAP) are measured by a pulmonary artery flotation catheter (52) and the the arterial pressure (AoP) measured by a catheter 53 in an artery e.g. in the arm, of the patient. The processing unit may be connected to a printer 57 or a visual display unit (VDU) 58 which can produce a graphical display of the either the left or the right ventricular function or both functions simultaneously. The VDU and the printed display may be arranged to display coordinate axes 60 representing pressure drop and cardiac output for each ventricular function and a target area 61 representing normal ranges of coordinate values. The VDU and the printed display may be arranged to plot the status point 62, representative of a single set of coordinate values at any point in time, on the coordinate axis or a series of status points at sampled over a period of time. Thus the changing haemodynamic state of the patient may be recorded and both the magnitude and the direction of any abnormalities may be illustrated. Alternatively, the apparatus may be arranged to indicate that the status point has left the target area, for example by sounding an alarm or making a visual indicator on the screen or printer.

Following the correction of any gross abnormalities in the haemodynamic state of a patient it may be possible to monitor only the left ventricular function. Any patient with primary or secondary right sided failure must have the failure corrected before monitoring the left ventricular function alone. One skilled 1n the art will be able to assess the haemodynamic state of a patient, apply treatment strategies and monitor the

subsequent response to such treatments. The treatments which may be applied will depend upon the position of the status point in each nomogram and the nomograms may be arranged to display suggested treatment strategies. In tables 1 and 2 the letters refer to areas of the left and right sided nomograms (figures 4 and 8) and the suggested treatments are given in order of priority, as will be appreciated by one skilled in the art.

Left Ventricular Function Nomogram - figure 4

Haemodynamic Territory Suggested Treatment

A Normalise Pre-load bounded by lines 10 and 11 Increase Inotropes

B Vasodilate bounded by lines 10 and 16 Normalise Pre-load Increase Inotropes

C Vasodilate bounded by lines 11 and 16 Normalise Pre-load

D Vasodilate bounded by lines 11 and 14

E Reduce Inotropes bounded by line 17 Reduce Pre-load

F Vasoconstrict bounded by lines 10 and 17

G Vasoconstrict bounded by lines 10 and 16 Normalise Pre-load j

H ^' Vasoconstrict bounded by lines 11 and 16 Normalise Pre-load _j Increase Inotropes j

Table 1

Right Ventricular Function Nomogram - Figure 8

Haemodynamic Territory Sugσested Treatment

S Normalise Pre-load bounded by line 34 Increase Inotropes

T Normalise Pre-load bounded by lines 30, 32 and 34

U Pulmonary Dilation bounded by lines 32, 34 and 35 Normalise Pre-load

V Pulmonary Dilation bounded by lines 32 and 35 Reduce Inotropes Reduce Pre-load

W Reduce Inotropes bounded by lines 32 and 35 Reduce Pre-load

Table 3

There are three specific interventions that will have particular effects. These effects are Illustrated on figure 10 and are:-

1. Adjustment of the left or right atrial pressure will tend to move the status point across the lines of constant ventricular power, along line 65. The angle and magnitude of the movement will depend on the functional integrity of the heart.

2. The addition of withdrawal of inotropes which alter the contractility of the heart will also produce a similar movement but will also depend on the receptor status of the myocardium.

3. Adjustments to the pulmonary or systemic vascular resistance by the use of dilators or constrictors will tend to move the status point along the lines of constant ventricular power, along line 66. The magnitude and direction of the movement will depend on the compliance of the vascular beds.

Any heart which is producing more than the minimum power output should be capable of moving inside the target area by judicious use of dilators and constrictors alone, but optimisation of the pre-load may also be beneficial. Gross abnormalities of the vascular resistance will often influence the power output by altering the myocardial supply/demand ratio, so that optimisation may cause shifts of the status point across power bands in the first instance. If the minimum power outputs are unattainable at maximum pre-loads of 12 to 15 mmHg, then the use of inotropes may be indicated. Myocardial overdrive (for example where the left ventricular power output exceeds 1.0 Watt at rest) may enable inotropes to be reduced and pre-load lowered.

There are a number of clinical settings where the use of the invention can be helpful in patient management and in the objective assessment of cardiac function, for exa ple:-

1. Cardiogenic shock is usually complicated by inappropriate physiological responses to a low output state. Use of the invention may also be helpful when determining that the implementation of a circulatory mechanical assist is required. 2. Un1 or biventricular failure is often difficult to quantify. Use of the left and right sided nomograms may be helpful 1n determining and quantifying the interaction between ventricles. Right sided failure may be indicated by a steep positive curve, whilst left sided failure may be indicated by a marked negative curve, on the right sided nomogram in response to an increased pre-load. 3. Impedance matching between the ventricle and it's load can be aided by the invention. It should be borne in mind that the impedance is frequency dependent and impedance matching requires a dynamic measurement of the ventricular power, which can be achieved by measuring dynamic pressure and flow waveforms and performing the appropriate calculations on the harmonics of the waveforms.

4. Donor heart function is complicated by the humeral and hormonal effects of brain death in the donor. This may give rise to abnormal haemodynamics and the invention may be used to provide objective data upon which to base preoperative management and donor heart selection.

The following examples are taken from donors being considered for retrieval of their hearts for transplantation and indicate the changes in the haemodynamic state following an alteration in treatment between readings. The examples indicate the type of assessment that may be made by a skilled clinician using the objective data assimilated according to the invention; it will be appreciated that the skilled clinician will use more that the nomograms to make a diagnosis.

Example 1 - Figure 11

A 25 year old male had been admitted and ventilated for 30 hours following a subarachnoid haemorrhage. He had a chest infection and ECG changes including 'T' wave inversion in lead 1 and AVL. The patient required 6 mcg/kg/min of Dopamine and 6 mcg/kg/min of Dobutamine and had a PCWP (measured In place of LAP) of 17 mmHg at status point 1 in figures 11 and 11a. The patient demonstrated Inotrope dependency on temporary withdrawal of all inotropes, at point 2, and the heart was therefore deemed unsuitable for transplantation because the LVPo dropped below the acceptable level on withdrawal of the inotropes.

Example 2 - Figure 12

A 48 year old female with massive extra-dural haemorrhage and right inter-cranial haemorrhage following a fall. The patient had a PCWP of 4 mmHg and no inotropic support, although the SVR wa:T 2,000 dynes.s.cπr ⁵ , status point 1, figure 12 and 12a. Sodium nitroprusside was initiated at 1.4 mcg/kg/min and prostacyclin initiated at 4.8 ng/kg/min. The SVR reduced to 870 dynes.s.cm ^-5 , status point 2, with a slight improvement in power. The sodium nitroprusside was reduced to 0.9 mcg.kg/min

and the SVR increased to 1,000 dynes.s.cm---', status point 3, again with a slight improvement in power. Vasodilation in this case caused movement down the line of constant power with some minimal increase in power due to an improved supply/demand ratio.

Example 3 - Figure 13

A 17 year old male had been admitted for 80 hours with a fractured skull following a road traffic accident. On full monitoring it was found that the PCWP was 23 mmHg with the heart at the top of the function curve, status point 1, figure 13 and 13a. Overenthusiastic venesection reduced the PCWP to 9 mmHg, status point 2. Additional volume increased the PCWP to 11 mmHg and the status point moved into the middle of the optimum area, status point 3.

Example 4 - Figure 14

A 19 year old female had been involved in a road traffic accident and had required resuscitation by the ambulance crew. Extensive haemorrhaging had occurred due to a lacerated liver and 12 units of blood and fresh frozen plasma were transfused. On inspection the RAP was 25 mmHg, the PCWP was 11 mmHg and the PVR was 240 dynes.s.cm ^"* - ^* , status point 1, figure 14 and 14a. Arterial saturation was 79% when ventilated with 100% oxygen. There was obvious right ventricular failure secondary to an elevated PVR, probably due to hypoxia. The airway was cleared resulting in an increase in arterial saturation to 99.8% leading to a dramatic drop in PVR to 80 dynes.s.cm-- ^*5 , status point 2. Right ventricular function improved dramatically with an RAP of 13 mmHg and PCWP of 10 mmHg. Table 3 indicates the raw data used to construct the nomograms for the above examples.

Example Point RAP PAP PCHP/LAP AoP CO

1 1 11 22 17 76 7.13

2 13 23 17 46 3.93

2 1 2 11 4 117 4.50

2 5 14 6 90 7.80

3 5 14 5 97 7.2

3 1 10 32 23 92 8.60

2 8 16 9 62 3.79

3 7 20 11 69 4.72

4 1 25 27 11 60 5.23

2 13 16 10 78 5.86

Table 3

References for determining maximum and minimum criteria.

Cardiac Output

Braunwald E. Heart Disease. A textbook of cardiovascular medicine. Saunders, Third edition, Vol 2, Ch 38. Forrester OS et al . Medical therapy of acute myocardial infarction by application of haemodynamic subsets. N. Engl. 0. Med. 1976; 295, 1404.

Left Ventricular Pressures and Resistances

Cooper DKC, Novltzky D. The Transplantation and Replacement of Thoracic Organs. Kluwer Academic Publishers 1990, Ch 6. Mackersie RC, Bronsther OL, Shackford SR. Organ Procurement in Patients with Fatal Head Injuries. Ann. Surg. 1991; 213(2), 143.

Canivet OL et al . Fluid Management and Plasma Renin Activity in Organ Donors. Transplant Int. 1989; 2, 129.

Right Ventricular Pressures

Erlkson KW et al . Influence of Pre-operative Transpulmonary Gradient on Late Mortality after Orthotropic Heart Transplantation. 3 Heart Transplant 1990; 9,526. Kells CM et al . Cardiac Function after Domino-Donor Heart Transplantation. Am. 0. Cardiol. 1992; 69, 113.