Cardiac Contractility II. In vivo assessment Tams Radovits MD, PhD - PowerPoint PPT Presentation

Cardiac Contractility II. In vivo assessment Tamás Radovits MD, PhD associate professor Heart and Vascular Center Semmelweis University Budapest 2018.

Anatomy of the heart

Anatomy of the heart II. Atrioventricular valve Semilunar valve

Anatomy of the heart III. Excitatory and conductive system

Cardiac biomechanics • Basic rules: – Liquid (blood) is incompressible – Direction of flow is determined by the pressure gradient – Valves open/close passively, depending on the pressure on both sides – Valves prevent backflow of blood • Cardiac cycle: – alternation of systole (contraction) and diastole (relaxation) – Cardiac events occuring from the beginning of one heartbeat till the beginning of the next one

Cardiac cycle I. 1. (Double) diastole (passive diastolic filling) • after repolarisation, the atrium (A) and the ventricle (V) are relaxed for 0.4s • P central veins >P atrium > P ventricle  atrioventricular valve is open  blood flows continually from veins to A then to V (passive diastolic filling of V, 80% of total V filling). • Semilunar valve is closed • Volume of ventricle increases, pressure of ventricle remains low • phases: 1: rapid filling, 2: diastasis (slow filling) • 2. Atrial systole • action potential of sinus node  depolarization spreads to the atrial myocardium  atrial contraction (ECG: p-wave) • V is still in diastole  inflow of blood into V (20% of total V filling) • P atrium increases (+5mmHg, „a” wave), P ventricle increases (+4mmHg) • Volume of atrium decreases, volume of ventricle increases (at the end of diastole: end-diastolic volume , EDV: 120ml)

Cardiac cycle II. 3. Systole (of the ventricle) 0.27s • Atrial systole is followed by the depolarisation of the ventricular myocardium (ECG: QRS-complex)  contraction of the ventricle At the beginning of ventricular systole, the ventricular pressure rises  • closing of the atrioventricular valve  1st heart sound • Aortic diastolic pressure keeps the semilunar valve closed •  1st phase of systole: isovolumic contraction (or pre-ejection phase, 0.05s) P ventricle rises rapidly, (+70mmHg), ventricular volume is unchanged • P ventricle rises and reaches the aortic diastolic pressure (80mmHg) •  semilunar valve opens  2nd phase of systole: ejection (0.22s) • Parallel rise of ventricular and aortic pressure • Decrease of ventricular volume (ejection of 70ml blood into the aorta: stroke volume , SV) • 2 phases of ejection: period of rapid ejection (first third, 70% of SV), period of slow ejection (30% of SV) • At the end of ejection, 50ml blood remains in the ventricle ( end-systolic volume , ESV)

Cardiac cycle III. 3. Systole (of the ventricle) cont. • Ejection fraction (EF): the fraction of the end-diastolic volume that is ejected during systole • EF= SV/EDV ( EF= 0.5-0.7, or 50-70% ) • Pressure rise in the aorta depends on – Stroke volume – Elasticity/distensibility of the aorta – Rate of blood flow to the periphery • Aortic systolic pressure: 120-130 mmHg, Pulmonary artery systolic pressure: 24 mmHg • The whole SV ejected into the aorta does not flow towards the periphery during systole. The aorta distends during systole and acts as an elastic reservoir, and recoils during diastole (Windkessel effect)  continuous blood flow towards the periphery during the whole cardiac cycle • Repolarization begins suddenly (ECG: T wave)  relaxation of ventricular myocardium starts  P ventricle falls rapidly  P aorta > P ventricle  closing of semilunar valve  2nd heart sound

Cardiac cycle IV. 4. Ventricular diastole Both the semilunar and atrioventricular valves are closed  ventricle is a • closed chamber, no volume change, pressure falls rapidly  Isovolumic relaxation • P atrium increases due to the continuous inflow of blood from the central veins, P ventricle falls  P atrium > P ventricle  atrioventricular valve opens  ventricular filling

Cardiac cycle V. – Summary of the phases 1. Systole (0.27s) Isovolumic contraction (0.05s) Ejection (0.22s) Period of rapid ejection Period of slow ejection 2. Diastole (0.53s) Isovolumic relaxation (0.08s) Ventricular filling (0.45s) Passive diastolic filling Rapid inflow Diastasis Atrial systole

Left ventricular pressure-volume loop

Basic hemodynamic parameters I. Heart rate (HR) 70/min Left ventricular (LV) pressures LV maximal systolic pressure (LVSP) 120mmHg LV end-systolic pressure (LVESP) 100mmHg LV end-diastolic pressure (LVEDP) 8mmHg LV volumes LV end-diastolic volume (LVEDV) 120ml LV end-systolic volume (LVESV) 50ml Stroke volume (SV=LVEDV-LVESV) 70ml Cardiac Output (CO=SV* HR) 5 l/min Cardiac index (CI=CO/body surface area) 2.6-4.2 l/min/m 2 Ejection fraction (EF=SV/LVEDV) 0.5-0.7, or 50-70% Left atrial pressure (estimated by pulmonary capillary wedge pressure, PCWP) 5-12mmHg

Basic hemodynamic parameters II. Systolic aortic (arterial) pressure 120mmHg Diastolic aortic (arterial) pressure 80mmHg Mean arterial pressure (MAP ≈ 1/3 systol ic + 2/3 diastolic arterial pressure) 90-100mmHg Total peripheral resistance (TPR= perfusion pressure/CO; TPR ≈ MAP/CO) 18mmHg/(l/min) Stroke work (or external work, area of the P-V loop) (SW ≈ LVESP*SV) Right ventricle and pulmonary circulation: analogue to the left heart, but lower pressures Right ventricular (RV) pressures RV maximal systolic pressure (RVSP) 24mmHg RV end-diastolic pressure (RVEDP) 4mmHg Right atrial pressure ( ≈ central venous pressure, CVP) 1-6mmHg Systolic pulmonary arterial pressure 24mmHg Diastolic pulmonary arterial pressure 9mmHg SV values of the LV and RV are equal on average

Regulation of cardiac pump function

Regulation of cardiac pump function • 1.: PRELOAD (~filling) - Frank-Starling mechanism the degree of tension on the myocardium when it begins to contract - the greater is the myocardium is stretched during filling, the greater is the force of contraction and the greater is the SV - possible subcellular explanations: -optimal sarcomere-length (Ca 2+ -sensitivity depends on sarcomere length) -mechanosensitive Ca 2+ -channels

Regulation of cardiac pump function • 2.: AFTERLOAD (~ aortic pressure) the load against which the myocardium exerts its contractile force - increase of afterload leads to a transient decrease of SV (dotted loop) - due to the unchanged inflow of blood EDV increases, resulting in stronger contraction and normalisation of SV (red loop)

Regulation of cardiac pump function • 3.: HEART RATE - Bowditch effect (Treppe phenomenon) – Heart rate↑  force of contractions↑  cardiac output ↑ – At extreme high HR force of contractions ↓ – Mechanism: inability of the Na + /K + -ATPase to keep up with influx of Na + at higher heart rates  higher ic. Ca 2+  stronger contractions

Regulation of cardiac pump function • 4.: CONTRACTILITY - intrinsic ability of the myocardium to contract -increased contractility -increased force and velocity of contractions -increased pressure generation by the ventricle -increased SV and CO Inotropic effect : change of force of contractions Cellular mechanisms: -increased Ca 2+ transient -increased Ca 2+ sensitivity of the contractile apparatus

Regulation of cardiac pump function Contractility is influenced by: • Structure of the myocardium • Metabolic state of the myocardium • Ion concentrations • Neurohumoral effects • Sympathetic and • Parasympathetic activation • Temperature • Drugs • …

Regulation of cardiac pump function • Sympathetic and parasympathetic activation alters contractility

Regulation of cardiac pump function • Beta-adrenergic agonists increase contractility - mechanisms:

Assessment of contractility in vivo • … is difficult! • No exact parameters • No proper non-invasive approaches • Ideal contractility parameter is: – independent of preload – independent of afterload – independent of heart rate – sensitive to inotropic effects

Conventional contractility parameters • Ejection fraction (EF) - SV/EDV - dependent on preload and afterload - widely used in the clinical routine for determining contractility - advantage: easy to measure (echocardiography) • Maximal rate of systolic pressure increment in the LV (dP/dt max ) - requires ventricular catheterisation - refers to the isovolumic contraction phase - dependent on loading conditions

Precise assessment of contractility LV pressure-volume analysis during preload reduction (caval vein occlusion)

Load-independent contractility parameters I. ESPVR (End-Systolic-Pressure-Volume-Relationship) Slope of the line connecting end-systolic points of P-V loops during caval vein occlusion maneuver Independent of pre- and afterload Control Increased contractility

Load-independent contractility parameters II. PRSW (Preload-Recruitable-Stroke-Work) • Slope of the linear relationship between stroke work and end- diastolic volume during caval vein occlusion maneuver • Independent of pre- and afterload • Very sensitive to inotropic changes • This relationship is always linear • Gold standard index of LV contractility in vivo