This lecture summarizes the chronology and rationale that led to the discovery of angiotensin-(1-... more This lecture summarizes the chronology and rationale that led to the discovery of angiotensin-(1-7) as a hormone that, in its own right, opposes the vasoconstrictor and proliferative actions of angiotensin II. The work discussed here additionally analyzes the newest findings on angiotensin-converting enzyme 2, the angiotensin-converting enzyme homologue that efficiently hydrolyzes angiotensin II into angiotensin-(1-7). Both components of this system may significantly influence our future perspective of the role of the renin–angiotensin system, not just in terms of its role in the regulation of cardiovascular and renal function but, moreover, as regulators of a vast array of disease processes in which inflammation and immune mechanisms play a role.
Pulmonary arterial hypertension (PAH) is an uncommon but lethal and progressive disease in which ... more Pulmonary arterial hypertension (PAH) is an uncommon but lethal and progressive disease in which prostacyclin, nitric oxide and endothelin-1 pathways are disturbed and contribute to the pathophysiology of this disease. Endothelin receptor antagonists are a class of drugs that have been approved as PAH therapy. Macitentan is a lipophilic, tissue specific, dual receptor antagonist with a higher potency than bosentan and a reduced risk of hepatic injury. Macitentan has shown a reduction in morbidity and mortality due to PAH at long-term follow-up and improvements in hemodynamics, exercise capacity and functional class at the short term. Its main adverse events are nasopharyngitis, bronchitis and an increased risk of anemia. We review the clinical data of macitentan and its use in PAH.
Pulmonary Circulation and Pulmonary Vascular Disease, 2017
Objective: To analyze data prospectively collected from Mexican-mestizo patients who participated... more Objective: To analyze data prospectively collected from Mexican-mestizo patients who participated in randomized clinical trials between 2000-2016 in Mexico City. Results: Only data from 100 patients is presented. Idiopathic (iPAH, 60%), connective tissue disease PAH (CTD, 15%) and congenital heart disease-PAH. The latter was divided in corrected(12%) and non-corrected patients(n=13). 2% of iPAH were vasoresponders. Median age at RHC was 29 years, but iPAH and CTD tended to be older. BMI was 23.84 with no differnece between groups. Thyroid disorders were most frequent co-morbidity. In RHC, mPAP was signficantly higher in congenital-PAH group than other types. iPAH had lowest median cardiac output. 22% of patients were diagnosed before 2000, but only 6.1% treated with nifedipine before 1998. All patients received PAH pharmacotherapy, but time from diagnostic RHC to first use of drug was significantly different between and within groups. Endothelin receptor antagonists were most frequent drug used, followed by PDE-5 inhibitor. Except for CTD-PAH, significant improvement in functional class was found for all groups within 1-year after treatment. 30-53% received combination therapy. Corrected congenital-PAH had longest median time until addition of second drug, followed by iPAH and CTD. 10-40% had a drug class switch due to lack of supply, end of randomized or extended open-label trial phase. Cumulative survival from drug start to death (or censored at last oupatient visit) for 1,3,5 and 10 years were as follows: iPAH excluding vasoresponders (100%,95%,93%,87%), CTD (77%,66%,55%,0%) and corrected-congenital PAH (100%,92%,83%,75%). All Eisenmenger9s remain alive.
Purpose of review The purpose of this review is to demonstrate advances in the medical treatment ... more Purpose of review The purpose of this review is to demonstrate advances in the medical treatment of pulmonary arterial hypertension (PAH). Reviewed will be the evidence that favors the use of risk assessment in the treatment of PAH. Optimization of combination therapy depending on the risk or worsening will be reviewed. Finally, recent advances in new treatment strategies will be mentioned. Recent findings The use of therapies in sequence or in combination for the treatment of PAH has been shown to decrease morbidity and mortality. Tailoring these treatment strategies to a risk of worsening has been shown to decrease mortality and time to clinical worsening because of PAH. In addition, there have been several advances in the development of other medications separate from the three known pathogenic pathways in PAH.
Despite advances in pharmacologic treatment, pulmonary arterial hypertension (PAH) remains a fata... more Despite advances in pharmacologic treatment, pulmonary arterial hypertension (PAH) remains a fatal disease. In recent years, surgical/interventional approaches including balloon dilation atrial septostomy and Potts anastomosis have been applied to improve the hemodynamic variables associated with right ventricular failure in the setting of PAH. These interventions may improve quality of life and prolong survival in this population. In this review, we will discuss the role of these 2 therapeutic alternatives in the management of PAH.
Pulmonary Arterial hypertension (PAH) is a chronic and progressive disease characterized by an in... more Pulmonary Arterial hypertension (PAH) is a chronic and progressive disease characterized by an increase in pulmonary vascular resistance due to severe remodeling of the small pulmonary arteries. In PAH, the endothelial cells fail to maintain their homeostatic balance, with the consequent impaired production of vasodilators and over-expression of vasoconstrictors and proliferators. Current treatment of PAH is based on the discovery of three main pathways of endothelial dysfunction (prostacyclin, nitric oxide and endothelin-1), and includes drugs such as prostacyclin analogs, phosphodiesterase-5 inhibitors and endothelin receptor antagonists (ERAs). Recently approved drugs that act through these classic pathways include riociguat (cyclic GMP stimulator) and macitentan (a tissue specific dual ERA). However, several new drugs and new pathways are under study. New targeted therapies include tyrosine kinase inhibitors, Rho kinase inhibitors and serotonin receptor blockers. There are now ten drugs approved for the treatment of PAH that, alone or in combination, have changed the natural history of this disease. The new drugs will allow us to further modified the patients' life expectancy and move towards a cure.
Archivos Peruanos de Cardiología y Cirugía Cardiovascular, 2021
Objetivos. El objetivo del estudio fue describir las características clínicas y la relación entre... more Objetivos. El objetivo del estudio fue describir las características clínicas y la relación entre la severidad de la hipertensión arterial pulmonar (HAP) y el grado de insuficiencia renal. Materiales y métodos. Se realizó un estudio observacional retrospectivo en el cual se analizaron las historias clínicas físicas y electrónicas de 60 pacientes mayores de 18 años con diagnóstico de hipertensión arterial pulmonar. Resultados. El 11,4% de pacientes con HAP severa empeoraron su función renal a los 6 meses y el 13,6% al año. En contraste, en el grupo de pacientes con HAP moderada, 18,8% empeoraron a los 6 meses y el 12,5% empeoraron al año. La TFG al año fue de 54,15 mL/min/1,73 m2 en pacientes con HAP moderada y en la HAP severa de 73,55 mL/min/1,73 m2. Conclusiones. Los resultados de esta investigación sugieren que el deterioro de la función renal tendría relación con la severidad de la hipertensión arterial pulmonar.
This lecture summarizes the chronology and rationale that led to the discovery of angiotensin-(1-... more This lecture summarizes the chronology and rationale that led to the discovery of angiotensin-(1-7) as a hormone that, in its own right, opposes the vasoconstrictor and proliferative actions of angiotensin II. The work discussed here additionally analyzes the newest findings on angiotensin-converting enzyme 2, the angiotensin-converting enzyme homologue that efficiently hydrolyzes angiotensin II into angiotensin-(1-7). Both components of this system may significantly influence our future perspective of the role of the renin–angiotensin system, not just in terms of its role in the regulation of cardiovascular and renal function but, moreover, as regulators of a vast array of disease processes in which inflammation and immune mechanisms play a role.
Pulmonary arterial hypertension (PAH) is an uncommon but lethal and progressive disease in which ... more Pulmonary arterial hypertension (PAH) is an uncommon but lethal and progressive disease in which prostacyclin, nitric oxide and endothelin-1 pathways are disturbed and contribute to the pathophysiology of this disease. Endothelin receptor antagonists are a class of drugs that have been approved as PAH therapy. Macitentan is a lipophilic, tissue specific, dual receptor antagonist with a higher potency than bosentan and a reduced risk of hepatic injury. Macitentan has shown a reduction in morbidity and mortality due to PAH at long-term follow-up and improvements in hemodynamics, exercise capacity and functional class at the short term. Its main adverse events are nasopharyngitis, bronchitis and an increased risk of anemia. We review the clinical data of macitentan and its use in PAH.
Pulmonary Circulation and Pulmonary Vascular Disease, 2017
Objective: To analyze data prospectively collected from Mexican-mestizo patients who participated... more Objective: To analyze data prospectively collected from Mexican-mestizo patients who participated in randomized clinical trials between 2000-2016 in Mexico City. Results: Only data from 100 patients is presented. Idiopathic (iPAH, 60%), connective tissue disease PAH (CTD, 15%) and congenital heart disease-PAH. The latter was divided in corrected(12%) and non-corrected patients(n=13). 2% of iPAH were vasoresponders. Median age at RHC was 29 years, but iPAH and CTD tended to be older. BMI was 23.84 with no differnece between groups. Thyroid disorders were most frequent co-morbidity. In RHC, mPAP was signficantly higher in congenital-PAH group than other types. iPAH had lowest median cardiac output. 22% of patients were diagnosed before 2000, but only 6.1% treated with nifedipine before 1998. All patients received PAH pharmacotherapy, but time from diagnostic RHC to first use of drug was significantly different between and within groups. Endothelin receptor antagonists were most frequent drug used, followed by PDE-5 inhibitor. Except for CTD-PAH, significant improvement in functional class was found for all groups within 1-year after treatment. 30-53% received combination therapy. Corrected congenital-PAH had longest median time until addition of second drug, followed by iPAH and CTD. 10-40% had a drug class switch due to lack of supply, end of randomized or extended open-label trial phase. Cumulative survival from drug start to death (or censored at last oupatient visit) for 1,3,5 and 10 years were as follows: iPAH excluding vasoresponders (100%,95%,93%,87%), CTD (77%,66%,55%,0%) and corrected-congenital PAH (100%,92%,83%,75%). All Eisenmenger9s remain alive.
Purpose of review The purpose of this review is to demonstrate advances in the medical treatment ... more Purpose of review The purpose of this review is to demonstrate advances in the medical treatment of pulmonary arterial hypertension (PAH). Reviewed will be the evidence that favors the use of risk assessment in the treatment of PAH. Optimization of combination therapy depending on the risk or worsening will be reviewed. Finally, recent advances in new treatment strategies will be mentioned. Recent findings The use of therapies in sequence or in combination for the treatment of PAH has been shown to decrease morbidity and mortality. Tailoring these treatment strategies to a risk of worsening has been shown to decrease mortality and time to clinical worsening because of PAH. In addition, there have been several advances in the development of other medications separate from the three known pathogenic pathways in PAH.
Despite advances in pharmacologic treatment, pulmonary arterial hypertension (PAH) remains a fata... more Despite advances in pharmacologic treatment, pulmonary arterial hypertension (PAH) remains a fatal disease. In recent years, surgical/interventional approaches including balloon dilation atrial septostomy and Potts anastomosis have been applied to improve the hemodynamic variables associated with right ventricular failure in the setting of PAH. These interventions may improve quality of life and prolong survival in this population. In this review, we will discuss the role of these 2 therapeutic alternatives in the management of PAH.
Pulmonary Arterial hypertension (PAH) is a chronic and progressive disease characterized by an in... more Pulmonary Arterial hypertension (PAH) is a chronic and progressive disease characterized by an increase in pulmonary vascular resistance due to severe remodeling of the small pulmonary arteries. In PAH, the endothelial cells fail to maintain their homeostatic balance, with the consequent impaired production of vasodilators and over-expression of vasoconstrictors and proliferators. Current treatment of PAH is based on the discovery of three main pathways of endothelial dysfunction (prostacyclin, nitric oxide and endothelin-1), and includes drugs such as prostacyclin analogs, phosphodiesterase-5 inhibitors and endothelin receptor antagonists (ERAs). Recently approved drugs that act through these classic pathways include riociguat (cyclic GMP stimulator) and macitentan (a tissue specific dual ERA). However, several new drugs and new pathways are under study. New targeted therapies include tyrosine kinase inhibitors, Rho kinase inhibitors and serotonin receptor blockers. There are now ten drugs approved for the treatment of PAH that, alone or in combination, have changed the natural history of this disease. The new drugs will allow us to further modified the patients' life expectancy and move towards a cure.
Archivos Peruanos de Cardiología y Cirugía Cardiovascular, 2021
Objetivos. El objetivo del estudio fue describir las características clínicas y la relación entre... more Objetivos. El objetivo del estudio fue describir las características clínicas y la relación entre la severidad de la hipertensión arterial pulmonar (HAP) y el grado de insuficiencia renal. Materiales y métodos. Se realizó un estudio observacional retrospectivo en el cual se analizaron las historias clínicas físicas y electrónicas de 60 pacientes mayores de 18 años con diagnóstico de hipertensión arterial pulmonar. Resultados. El 11,4% de pacientes con HAP severa empeoraron su función renal a los 6 meses y el 13,6% al año. En contraste, en el grupo de pacientes con HAP moderada, 18,8% empeoraron a los 6 meses y el 12,5% empeoraron al año. La TFG al año fue de 54,15 mL/min/1,73 m2 en pacientes con HAP moderada y en la HAP severa de 73,55 mL/min/1,73 m2. Conclusiones. Los resultados de esta investigación sugieren que el deterioro de la función renal tendría relación con la severidad de la hipertensión arterial pulmonar.
Uploads
Papers by Nayeli Zayas