CC Cardiol Croat Cardiologia Croatica Cardiol. Croat. 1848-543X 1848-5448 Croatian Cardiac Society CC_13(11-12)_366 10.15836/ccar2018.366 Extended Abstract Significance of platelet function in pulmonary hypertension secondary to chronic systolic heart failure Važnost funkcije trombocita u sekundarnoj plućnoj hipertenziji uzrokovanoj kroničnim sistoličkim popuštanjem srca http://orcid.org/0000-0002-3197-2190PašalićMarijan*http://orcid.org/0000-0002-9346-6402SamardžićJurehttp://orcid.org/0000-0001-5979-2346SkorićBoškohttp://orcid.org/0000-0002-4772-5549ČikešMajahttp://orcid.org/0000-0001-7171-2206Ljubas MačekJanahttp://orcid.org/0000-0002-5052-6559LovrićDanielhttp://orcid.org/0000-0002-2599-553XJurinHrvojehttp://orcid.org/0000-0001-9101-1570MiličićDavor Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia ADDRESS FOR CORRESPONDENCE: Marijan Pašalić, Klinika za bolesti srca i krvnih žila, Klinički bolnički centar Zagreb, Kišpatićeva 12, HR-10000 Zagreb, Croatia. / Phone: +385-1-2367-467 / E-mail: marijan.pasalic@yahoo.com 112018 13 11-12 366 367 2510201805112018 2018 Croatian Cardiac Society KLJUČNE RIJEČI: plućna hipertenzijakronično sistoličko popuštanje srcapopuštanje lijeve klijetkefunkcija trombocita KEYWORDS: pulmonary hypertensionchronic systolic heart failureleft ventricular dysfunctionplatelet function

Background: Role of platelets in the pathogenesis of primary pulmonary hypertension is well established. Platelets act as mediators of vasoconstriction, inflammation, coagulation and vascular remodeling, all of which result in changes to the pulmonary circulation. (1-3) Although being a more common entity, data on pathogenesis of pulmonary hypertension (PH) secondary to heart disease remain scarce. The aim of this study was to shed light on the importance platelets have in the pathogenesis of PH secondary to chronic systolic heart failure (CSHF).
Patients and Methods: Measurement of platelet function was performed on 160 patients (57±10 years; 65% male) with CSHF admitted to University Hospital Centre Zagreb from October 2011 till October 2016. All patients were candidates for advanced treatment modalities and underwent right heart catheterization. Following the invasive measurement of hemodynamic parameters (including pulmonary artery pressure-PAP and vasoreactivity testing using alprostadil), blood samples were obtained from the pulmonary artery. Platelet aggregation induced by acetylsalicylic acid (ASPI), adenosine diphosphate (ADP), collagen (COL) or thrombin receptor activating peptide-6 (TRAP), was measured using Multiplate Analyzer.

Results: Most common causes of CSHF were ischemic and dilated cardiomyopathy (ICMP 45% vs DCMP 43%). As expected, all patients presented with decreased cardiac index and PH due to elevated left ventricular filling pressure (PCWP) (Table 1). Baseline aggregation tests showed reduced platelet activity, with ASPI being lower in patients with ICMP (p <0.001, due to acetylsalicylic acid therapy). COL test values were found to correlate significantly with PAP and PCWP (Figure 1). Vasoreactivity testing was performed in 26% of patients, and positive in 53% of cases (Table 2). Changes in PAP and PCWP correlated significantly with changes in ASPI and ADP tests (Figure 2).

Baseline hemodynamic parameters and aggregation tests.
Mean ± Standard Deviation
CVP 11.4 ± 5.8 mmHg
Mean PAP 34.9 ± 10.9 mmHg
PCWP 24.2 ± 8.4 mm Hg
CI 1.8 ± 0.5 L/min/m2
TPG 10.8 ± 5.3 mmHg
PVR 3.4 ± 2.0 Wood Units
ASPI 49.7 ± 33.4 U
ADP 51.7 ± 26.6 U
COL 42.9 ± 24.5 U
TRAP 73.7 ± 37.7 U
CVP – central venous pressure; PAP – pulmonary artery pressure; PCWP – pulmonary capillary wedge pressure; CI – cardiac index; TPG – transpulmonary pressure gradient; PVR – pulmonary vascular resistance; ASPI – acetylsalicylic acid induced aggregation test; ADP – ADP induced aggregation test; COL – collagen induced aggregation test; TRAP – thrombin receptor activating peptide-6 aggregation test

Regression plots showing linear interrelation between collagen induced aggregation (COL) and mean pulmonary artery pressure (PAP), i.e. left ventricular filling pressure (PCWP).

 Changes in hemodynamic parameters and aggregation tests following vasoreactivity testing with alprostadil.
Mean ± Standard Deviation
ΔMean PAP -8.8 ± 6.1 mmHg
ΔPCWP -6.3 ± 4.9 mm Hg
ΔCI +0.6 ± 0.8 L/min/m2
ΔTPG -2.9 ± 3.7 mmHg
ΔPVR -1.7 ± 1.5 Wood Units
ΔASPI -6.4 ± 17.1 U
ΔADP -10.7 ± 22.1 U
ΔCOL -6.7 ± 15.7 U
ΔTRAP -7.5 ± 19.4 U
TRAP 73.7 ± 37.7 U
CVP – central venous pressure; PAP – pulmonary artery pressure; PCWP – pulmonary capillary wedge pressure; CI – cardiac index; TPG – transpulmonary pressure gradient; PVR – pulmonary vascular resistance; ASPI – acetylsalicylic acid induced aggregation test; ADP – ADP induced aggregation test; COL – collagen induced aggregation test; TRAP – thrombin receptor activating peptide-6 aggregation test

Regression plots showing linear interrelation between changes in acetylsalicylic acid induced aggregation (ASPI) and in mean pulmonary artery pressure (PAP), i.e. changes in ADP induced aggregation (ADP) and in left ventricular filling pressure (PCWP), following vasoreactivity testing with alprostadil.

Conclusion: Platelets seems to play an important role in pathogenesis of PH secondary to CSHF. Further research on mechanisms and potential clinical significance of this interaction is warranted.

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