Authors

• Marijan Pašalić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-3197-2190
• Jure Samardžić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-9346-6402
• Boško Skorić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0001-5979-2346
• Maja Čikeš — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-4772-5549
• Jana Ljubas Maček — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0001-7171-2206
• Daniel Lovrić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-5052-6559
• Hrvoje Jurin — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-2599-553X
• Davor Miličić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0001-9101-1570

Abstract

**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 2 | | 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 FIGURE 1. Regression plots showing linear interrelation between collagen induced aggregation (COL) and mean pulmonary artery pressure (PAP), i.e. left ventricular filling pressure (PCWP). ### TABLE 2: 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 FIGURE 2. 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.

Keywords

pulmonary hypertension, chronic systolic heart failure, left ventricular dysfunction, platelet function

DOI

Literature

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