From the Guidelines
PDE5 inhibitors should generally be avoided in patients with significant left-to-right cardiac shunts, as they can worsen the hemodynamic consequences of such shunts by causing pulmonary vasodilation, which increases pulmonary blood flow and potentially exacerbates the shunt. The primary concern is that PDE5 inhibitors reduce pulmonary vascular resistance, which can increase the shunt fraction and potentially lead to pulmonary overcirculation, volume overload, and worsening heart failure 1. This occurs because these medications preferentially dilate vessels in well-ventilated areas of the lungs, potentially worsening ventilation-perfusion mismatch.
In some specific clinical scenarios with pulmonary hypertension and left-to-right shunts that have become bidirectional or right-to-left due to Eisenmenger physiology, PDE5 inhibitors might be considered under close specialist supervision, but this represents an exception rather than the rule and should only be initiated by cardiologists with expertise in adult congenital heart disease or pulmonary hypertension 1. The use of PDE5 inhibitors in these cases should be guided by the results of invasive hemodynamic assessment and the evaluation of pulmonary vasoreactivity, which carries prognostic significance 1.
Some key points to consider when evaluating the use of PDE5 inhibitors in patients with left-to-right shunts include:
- The size and direction of the shunt, as well as the presence of any associated pulmonary hypertension or Eisenmenger physiology 1
- The results of invasive hemodynamic assessment, including the measurement of pulmonary vascular resistance and the evaluation of pulmonary vasoreactivity 1
- The potential risks and benefits of PDE5 inhibitor therapy, including the risk of worsening heart failure and the potential for improvement in symptoms and exercise tolerance 1
- The need for close specialist supervision and monitoring, particularly in patients with complex congenital heart disease or pulmonary hypertension 1
Overall, the use of PDE5 inhibitors in patients with left-to-right cardiac shunts should be approached with caution and should only be considered in specific clinical scenarios where the potential benefits outweigh the risks.
From the Research
PDE5 Inhibitors in Left to Right Shunts
- PDE5 inhibitors, such as tadalafil and sildenafil, have been studied for their efficacy in treating pulmonary arterial hypertension (PAH) related to left to right shunt lesions 2, 3.
- A study published in 2007 found that tadalafil improved exercise capacity, reduced pulmonary artery systolic pressure, and improved WHO functional class in patients with PAH related to congenital left to right shunt lesions 2.
- A systematic review published in 2019 found that PDE5 inhibitors improved WHO functional class, six-minute walk distance, and reduced mortality in patients with PAH, including those with left to right shunt lesions 3.
- Another study published in 2010 found that sildenafil combined with sitaxsentan prevented shunt-induced PAH more effectively than sitaxsentan alone in an animal model of left to right shunt-induced PAH 4.
Mechanism of Action
- PDE5 inhibitors work by increasing vasodilation and inhibiting proliferation, which can help to reduce pulmonary vascular resistance and improve exercise capacity 3.
- The combination of PDE5 inhibitors with other therapies, such as endothelin receptor antagonists, may be more effective in preventing shunt-induced PAH than either therapy alone 4.
Clinical Implications
- PDE5 inhibitors may be a useful treatment option for patients with PAH related to left to right shunt lesions, particularly those who are not responding to other therapies 2, 3.
- Further research is needed to fully understand the clinical implications of using PDE5 inhibitors in patients with left to right shunt lesions, including the potential risks and benefits of long-term treatment 3, 4.