Microcirculatory Dysfunction in Acute Heart Failure

Abstract

Several conceptual frameworks have been proposed to explore the underlying pathogenesis of acute heart failure (AHF), and recently emerging evidence has suggested a potential impact of microcirculatory dysfunction. Numerous experimental and clinical studies have reported that microcirculation is altered in patients with AHF and cardiogenic shock (CS), and the extent of micro-vascular abnormalities has been correlated with organ dysfunction and mortality in AHF.

Although, the clinical consequences of macro-circulatory abnormalities, congestion or hypoperfusion, can lead to organ injury and failure of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain), the intermediary link between central hemodynamics and organ failure is represented by microcirculatory dysfunction. Multiple organ failure is common in AHF and CS patients, despite correction of mean arterial pressure and cardiac output. Furthermore, using global hemodynamic markers as target to therapy in AHF may not be sufficient to avoid subsequent organ failure. Direct monitoring of the microcirculation by using currently available techniques, in conjunction with global hemodynamic data can be expected to help in the understanding of the pathophysiology of microcirculatory dysfunction during AHF decompensation.

Although different treatment strategies, including pharmacological interventions and mechanical circulatory support (MCS), may theoretically improve microcirculatory dysfunction, AHF patients may present with distinct clinical condition, varying from hypertensive heart failure to CS, and the severity of microcirculatory alterations and the response to therapy may differ among these clinical conditions. Understanding the time-course of microcirculatory abnormalities during AHF decompensation may assist to guide the therapies, and may help to identify the optimal timing for MCS implant.

Clinical Case

A 68 year-old male presented in ED for prolonged chest pain and shortness of breath. Onset of pain was 4 h before admission with crescendo intensity.

Vital signs collected in ED showed: SBP = 80 mmHg, HR = 100/min, Respiratory rate = 28/min, T = 36.8 °C and peripheral O² saturation of 92%. Clinical examination focused on cardiovascular system revealed systolic murmur of mitral regurgitation 4/6 and S3 sound, pulmonary rales on both pulmonary fields, cold extremities and altered mental status.

No relevant medical history has been found for the patient, except a previous diagnosis of hypercholesterolemia and a recent Echocardiography documenting a moderate mitral regurgitation (MR).

ECG showed sinus rhythm (96/min) elevation of J point and ST elevation in V1–V5, with maximum of 8 mm in V2 (Fig. 13.5a) findings suggesting of anterior wall ST elevation myocardial infarction. Panel of biomarkers, available in 15 min since presentation, shows NT-pro-BNP = 3400 pg/ml, Hs-Troponin I = 885 ng/l and venous lactate of 5.2 mmol/l. Focus Echocardiography revealed LV global akinesia with severe MR, preserved RV function and did not detect other alternative causes of myocardial ischemia.

Fig. 13.5

(a) ST elevation in V3 lead before and after 90 min post PCI; (b) Coronary angiography before and after stenting (arrow shows the site of LAD occlusion); (c) Echocardiography showing dilated LV, apical akinesia, severe mitral regurgitation. (d) Chest X-ray showing moderate cardiomegaly, redistribution with upper vessel enlargement, perihilar haze, and bilateral pulmonary infiltrates

At this moment the diagnosis was anterior STEMI Killip IV class, and a loading dose of 180 mg Ticagrelor and 325 mg Aspirin were given to the patient.

We decided to activate the Heart Team for Cardiogenic Shock (CS) and to transfer the patient to Cath Lab. Due to hypoxia (SaO₂ = 92% under 4 L Oxygen flow) and high respiratory rate (30/min), and in the context of low SBP (75–80 mmHg), we considered first of all mechanical ventilation via IOT concomitant with administration of Dobutamine 5 mcg/kg/min. Furthermore, because of persistent low SBP, Heart Team decision was to implant a short-term mechanical circulatory support before coronary intervention, and only available option in that moment was Intra-Aortic Balloon Pump (IABP). Coronary angiography revealed occlusion of the first segment of LAD and interventionist performed direct stenting on culprit lesion with TIMI 3 flow (Fig. 13.5b). After angioplasty, the patient is transferred in Intensive care Unit (ICU) with IABP support 1:1 and mechanical ventilation. ECG performed at 90 min post angioplasty revealed resolution with more than 50% of ST elevation in V2 (Fig. 13.5a). BP was 85/45 mmHg and urinary output (via bladder catheter) was 30 ml/h. In ICU, information provided by Echocardiography confirmed severe MR, with LVEF 25% and good RV function (Fig. 13.5c). Blood lactate was 5.8 mmol/l and the result of other blood sample collected in ED showed Hemoglobin = 12.9 g/dl, WBC = 12,400/mm³, CK-MB = 76 serum creatinine = 1.9 mg/dl, ALT = 45UI/L, AST = 58UI/L, GGT = 71UI/L. A Swann-Ganz catheter was inserted and this option was determined by the need to adequately monitor hemodynamic parameters in a STEMI with IABP and persistent hypoperfusion secondary to CS. Invasive hemodynamic data showed Cardiac Index (CI) = 1.7 l/min/m², Pulmonary Capillary Wedge Pressure (PCWP) = 24 mmHg, Systemic Vascular Resistances (SVR = 21 Wood units) and Central Venous Pressure (CVP) = 14 mmHg (Fig. 13.6). IV vasoactive treatment included Dobutamine 7 mcg/kg/min and Furosemide 4 mg/h and it was continued for the next 18 h.

Fig. 13.6

Time course of the hemodynamic abnormalities and markers of organ dysfunction during the first 6 days of hospitalization. ALT alanine amin-transferaza, CI cardiac index, GGT gama glutamil transpeptidaza, IABP Intra-Aortic Baloon Pump, PCWP pulmonary capillary wedge pressure, SVR systemic vascular resistance

Chest X-ray detected moderate cardiomegaly, redistribution with upper vessel enlargement, perihilar haze, and bilateral pulmonary infiltrates (Fig. 13.5d).

In the day 2 in ICU, hemodynamic data showed increased of CI, but a substantial decrease in SVR (10 Wood units). This finding, in conjunction with worsening of multi-organ injury and radiological findings were supportive for the occurrence of Systemic Inflammatory Syndrome (SIRS) and dictated initiation of IV vasoconstrictor Norepinephrine at doses of 0.3 and then 0.5 mcg/kg/min. In the day 3, SBP was constantly higher than 95 mmHg with urinary output of 100 ml/h, CI increased at 2.4 l/min/m² and PCWP ranged between 15 and 17 mmHg (Fig. 13.6). Furthermore, blood lactate decreased at 2.2 mmol/l. TTE reported decreasing severity of MR. Dobutamine dose decreased at 5 mcg/kg/min. However, despite of the improving of the hemodynamics and of the global metabolic deficit, multi-organ injury remains persistent. During day 4, SBP and urinary output increased comparative with previous days and SVR increased toward normal value (1–14 Wood units) (Fig. 13.6). Blood lactate was 1.7 mmol/l. Norepinephrine dose was decreased and then stopped while Dobutamine dose has remained unchanged. Even if multi-organ injury continued to evolve, IABP assistance was switched from 1:1 to 2:1, without significant variations in SBP and without decrease of sub-aortic velocity time integral (VTI) at Echo. In the day 5, clinical examination reported no evident clinical signs of hypoperfusion and only mild congestion (basal pulmonary rales). All hemodynamic parameters have entered in normal range and to note, markers of organ dysfunction improved. IABP was switched at 3:1 during the next 6 h and then stopped. Dobutamine dose decreased at 2 mcg/kg/min. In the day six patient was transferred in Cardiology Unit. In Cardiology, the patient has been monitored clinically, ECG and biologic. Echocardiography demonstrated a substantial improvement in global contractility with EF = 35–37% and MR remained moderate. The markers of organ injury further decreased during hospitalization, but without attaining the normal values. The therapies with ACE-inhibitors and beta-blocker was initiated as soon as the patient became stable.

The patient was discharged in day 13 without signs of residual congestion and with a very good mobility. The patient and family have been instructed for effort and dietetic regimen, and a follow up visit at 2 weeks post discharge has been planned.

Comments

The clinical case is very illustrative for the in-hospital course of post MI-CS associated with SIRS and multi-organ injury (kidney, liver and lung). Multi-organ injury is the consequence of the various degree of microvascular abnormalities, and actually microcirculatory dysfunction is the main facilitator of organ injury/failure in CS.

In this case, the time course of microcirculatory alterations during hospitalization was longer than abnormalities in macro-hemodynamics, and tissue perfusion remained altered even after achievement of within-target cardiac index and SBP. In D3, D4 and D5 was a disconnection between improving in hemodynamic measurements and markers of organ injury.

Notably, although in this case revascularization has been associated to re-establishing of coronary microcirculatory perfusion, suggested by TIMI 3 flow and a >50% resolution of ST elevation, recovery of LV function is a long term process, unable to prevent early occurrence of multi-organ injury. In addition, the microcirculatory dysfunction initiated by systemic hypoperfusion to other organs may evolve independent of central hemodynamics.

Mechanical circulatory support (MCS) device has been used to reverse hemodynamic abnormalities and to maintain organ perfusion. Despite of the recent evidences showing limited outcome benefit, IABP remained the most utilized MCS. IABP has shown to improve coronary blood flow by augmenting coronary diastolic blood pressure and increasing cardiac index by reducing left ventricular afterload. These effects have been proved very useful in a patient with large anterior MI, where a substantial area of stunning may be responsible of persistent LV dysfunction despite of prompt revascularization, and furthermore in conditions of severe MR, potentially improved by decreasing afterload.

However, correction of global hemodynamic parameters by IABP did not cause a parallel improvement in microcirculatory perfusion and oxygenation of the organ systems, a condition referred to as a loss of hemodynamic coherence between macro- and microcirculation.

Beyond of technical success, reflected by improvement of macro-hemodynamics, preventing or limiting progression of microcirculatory dysfunction by MCS devices is a key factor responsible for improvement of outcome in patients with CS, and preservation of microcirculation with adequate tissue perfusion rather than maintenance of more normal arterial pressure is the crucial determinant of outcome.