cardiovascular-agents and Familial-Primary-Pulmonary-Hypertension

Pulmonary arterial hypertension (PAH) is a complex disease characterized by elevated pulmonary arterial pressure, pulmonary vascular remodelling and occlusive pulmonary vascular lesions, leading to right heart failure. Evidence from recent epidemiological studies suggests the influence of gender on the development of PAH with an approximate female to male ratio of 4:1, depending on the underlying disease pathology. Overall, the therapeutic strategy for PAH remains suboptimal with poor survival rates observed in both genders. Endogenous sex hormones, in particular 17β oestradiol and its metabolites, have been implicated in the development of the disease; however, the influence of sex hormones on the underlying pathobiology remains controversial. Further understanding of the influence of sex hormones on the normal and diseased pulmonary circulation will be critical to our understanding the pathology of PAH and future therapeutic strategies. In this review, we will discuss the influence of sex hormones on the development of PAH and address recent controversies.

Topics: Androgens; Animals; Cardiovascular Agents; Disease Susceptibility; Drug Resistance; Estrogens; Evidence-Based Medicine; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Incidence; Lung; Male; Models, Biological; Pulmonary Circulation; Receptors, Estrogen; Sex Characteristics; Vascular Resistance

Here we give an overview over treatment recommendations propagated by the European League Against Rheumatism (EULAR), EULAR Scleroderma Trials and Research Group, the German Network for Systemic Sclerosis, the European Respiratory Society, and the International Society of Heart and Lung Transplantation. As response to immunosuppressant (IS) therapy is usually weaker in systematic sclerosis (SSc) compared to other connective tissue disorders IS should be considered with caution. To prevent scleroderma renal crisis steroid doses should not exceed 15 mg/d. The definitive role of a number of new immunosuppressant drugs and the effects of autologous stem cell transplantation in systemic clerosis (SSc) have to be elucidated. Prostanoids, especially iloprost, are widely used as intravenous formulas for the treatment of severe Raynaud's phenomenon (RP) and digital ulcers (DU). Calcium antagonists are of limited therapeutic value. Bosentan, an oral endothelin receptor antagonists (ETRA), was shown to prevent new DU, but failed to heal existing DU, while the oral phopshodiesterase inhibitor (PDI) Sildenafil reduces the occurrence of RP and might be effective in ulcer healing. Combination therapies of PDI with ETRA are currently evaluated. Therapy of pulmonary arterial hypertension (PAH) is usually started as oral monotherapy, frequently using an ETRA. When this first-line therapy is not tolerated ETRA is substituted by PDI. If treatment goals are not reached with monotherapy combinationtherapy is started, for example by adding a PDI to an existing ETRA. In general, treatment of PAH in patients with connective tissue disease follows the same algorithms as in idiopathic PAH.

Topics: Antihypertensive Agents; Cardiovascular Agents; Drug Therapy, Combination; Europe; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Immunosuppressive Agents; Practice Guidelines as Topic; Raynaud Disease; Scleroderma, Systemic; Societies, Medical; Stem Cell Transplantation; Treatment Outcome; Ulcer

Levosimendan has anti-ischaemic effects, improves myocardial contractility and increases systemic, pulmonary and coronary vasodilatation. These properties suggest potential advantages in high-risk cardiac valve surgery patients where cardioprotection would be valuable. The present study investigated the peri-operative haemodynamic effects of prophylactic levosimendan infusion in cardiac valve surgery patients with low ejection fraction and/or severe pulmonary arterial hypertension.. Between May 2006 and July 2007, 20 consecutive patients with severe pulmonary arterial hypertension (systolic pulmonary artery pressure ≥ 60 mmHg) and/or low ejection fraction (< 50%) who underwent valve surgery in our clinic were included in the study and randomised into two groups. Levosimendan was administered to 10 patients in group I and not to the 10 patients in the control group. Cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (MPAP) were recorded for each patient preoperatively and for 24 hours following the operation.. CO and CI values were higher in the levosimendan group during the study period (p < 0.05). MPAP and PVR values were significantly lower in the levosimendan group for the 24-hour period (p < 0.05) and SVR values were significantly lower after 24 hours in both groups. When clinical results were considered, no difference in favour of levosimendan was detected regarding the mortality and morbidity rates between the groups.. Levosimendan improved the haemodynamics in cardiac valve surgery patients with low ejection fraction and/or severe pulmonary arterial hypertension, and facilitated weaning from cardiopulmonary bypass in such high-risk patients when started as a prophylactic agent.

Topics: Arterial Pressure; Cardiopulmonary Bypass; Cardiovascular Agents; Drug Administration Schedule; Familial Primary Pulmonary Hypertension; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemodynamics; Humans; Hydrazones; Hypertension, Pulmonary; Infusions, Parenteral; Pulmonary Artery; Pyridazines; Severity of Illness Index; Simendan; Stroke Volume; Time Factors; Treatment Outcome; Turkey; Vascular Resistance

Topics: Bosentan; Cardiovascular Agents; Dose-Response Relationship, Drug; Familial Primary Pulmonary Hypertension; Fingers; Humans; Hypertension, Pulmonary; Scleroderma, Systemic; Skin Ulcer; Sulfonamides; Treatment Outcome

Topics: Cardiovascular Agents; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Immunosuppressive Agents; Predictive Value of Tests; Raynaud Disease; Scleroderma, Systemic; Treatment Outcome; Ulcer

Intravenous periodic Iloprost is proven effective in the treatment of Raynaud phenomenon (RP) related to connective tissue disorder (CTD). It's well known that synthetic prostaglandins are effective drugs for the treatment of pulmonary arterial hypertension (PAH), and that PAH is frequently associated with CTD.. The aim of the study is to evaluate in the chronic effect of cyclic intravenous Iloprost on pulmonary arterial pressure.. We studied 17 consecutive patients with CTD (14 systemic sclerosis, 3 mixed CTD) and RP, at the entry and after at least 6months of treatment of RP with cyclic Iloprost. On both occasions, in all patients we performed transthoracic Doppler echocardiography and we determined NT-proBNP plasma levels, NYHA functional class, 6 Minute-Walk Distance (6MWD).. At follow-up (8.2±1.9months; range 6-12) mean values of pulmonary arterial systolic pressure (PASP) significantly decreased (from 32.2±9.2 to 29.2±7.6mmHg, p<0.04) and mean values of 6MWD significantly increased (from 407.5±101.5 to 448.3±89.9m, p<0.01). Moreover, we observed a significant direct correlation between PASP and NT-proBNP values and a significant inverse correlation both between NT-proBNP and 6MWD values and between PASP and 6MWD values.. Our results suggest that cyclic intravenous Iloprost may protect against the development or worsening of PAH in patients with CTD and RP.

Topics: Adult; Aged; Cardiovascular Agents; Connective Tissue Diseases; Dose-Response Relationship, Drug; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Male; Middle Aged; Pulmonary Wedge Pressure; Retrospective Studies; Time Factors; Treatment Outcome