Elevated Pulmonary Venous Pressure Research Articles

Haemodynamic contributors to pulmonary hypertension across the spectrum of adult congenital heart disease.

Adult congenital heart disease (ACHD) includes multiple disease states that predispose to pulmonary hypertension (PH). Haemodynamically, PH depends on abnormalities in three components: pulmonary blood flow (Qp), pulmonary vascular resistance (PVR) and pulmonary venous pressure (PVP). We sought to evaluate the prevalence and prognostic impact of individual haemodynamic abnormalities in ACHD. Retrospective study of ACHD patients undergoing cardiac catheterization at Mayo Clinic between 1999 and 2022 who were followed for the combined endpoint of death/heart transplantation. Among 1005 patients, 37% had mean pulmonary artery pressure (mPAP) ≥25 mmHg with more systemic ventricular disease, cyanotic disease and shunt lesions, highest N-terminal pro-B-type natriuretic peptide and worse right heart remodelling/dysfunction. Among those with biventricular circulation, elevated PVP, PVR and mPAP were associated with prognosis, but not increased Qp >8 L/min. However, risk of death/transplant increased for PVR only at ≥3 Wood units (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.17-4.15; p < 0.0001) and for mPAP only at ≥25 mmHg (HR 3.15, 95% CI 2.17-4.58; p < 0.0001), not at current recommended lower cutpoints. Combined abnormalities in PVP and PVR were associated with worst outcome (HR 5.20, 95% CI 3.55-7.63; p < 0.0001) with intermediate risk with either abnormality (HR 2.11, 95% CI 1.46-3.04; p < 0.0001). Findings were consistent across type of biventricular ACHD. Only with the Fontan (univentricular) circulation was a lower mPAP threshold (20 mmHg) associated with adverse outcomes. Elevation of mPAP ≥25 mmHg in ACHD with a biventricular circulation is prognostically important regardless of disease phenotype, but milder PH of 21-25 mmHg is not associated with adverse outcome unless associated with Fontan circulation. Elevation in PVP >15 mmHg and PVR ≥3 Wood units were each individually associated with mortality with combined abnormalities associated with greatest risk. Categorizing PH in ACHD by haemodynamic mechanism (PVR, PVP or Qp) allows meaningful prognostication, and may allow more unified study of targeted therapies across heterogeneous disease states in ACHD.

Grace Under Pressure.

Grace Under Pressure.

Abstract 14324: Low Pulmonary Venous Flow Drives Cpc-PH Development in a Pulmonary Venous Banding Swine Model of Cpc-PH

Introduction: Combined pre- and post-capillary pulmonary hypertension (Cpc-PH) is the most severe form of PH-LHF. While the impact of elevated left atrial and consequently elevated pulmonary venous (PV) pressure on Cpc-PH progression is well studied, little is known about how compromised PV flow secondary to LHF affects disease progression. To assess the hypothesis that decreased PV flow induces Cpc-PH, we developed a large animal model of Cpc-PH by decreasing PV flow independent of LHF. Methods: Survival pulmonary venous banding (PVB) surgery was performed on a large white male pig (9kg), which was then followed for 16 weeks. A pig of the same sex and weight underwent a sham operation as control. Both animals underwent cardiac 4D flow MRI and right heart catheterization (RHC) in a terminal study. Results: At 16 weeks post-surgery, MR imaging demonstrated that PVB decreased mean flow and peak velocity in the right (RIPV) and left inferior pulmonary veins (LIPV) and MPA (figure and table). PVB also decreased MPA relative area change (RAC) (table). RHC demonstrated elevated PCWP, mPAP, PVR, and decreased RV EF (table). Also, Fulton index was increased demonstrating RV hypertrophy (table). Discussion: In conclusion, this study utilized PVB to demonstrate the ability of decreased PV flow to drive Cpc-PH development in the absence of LHF. Our preliminary data suggest a low flow state in the lung can increase RV afterload and induce RV dysfunction. Further studies with a larger sample size are needed to confirm this pathomechanical mechanism. Figure. MRI image of PV confluence narrowing from the PVB. Insert shows flow rates from RIPV and LIPV (blue), across PVB (red), and into LA (green).

Two to Tango: Kidney-Lung Interaction in Acute Kidney Injury and Acute Respiratory Distress Syndrome.

Acute Kidney Injury (AKI) is an independent risk factor for mortality in hospitalized patients. AKI syndrome leads to fluid overload, electrolyte and acid-base disturbances, immunoparalysis, and propagates multiple organ dysfunction through organ “crosstalk”. Preclinical models suggest AKI causes acute lung injury (ALI), and conversely, mechanical ventilation and ALI cause AKI. In the clinical setting, respiratory complications are a key driver of increased mortality in patients with AKI, highlighting the bidirectional relationship. This article highlights the challenging and complex interactions between the lung and kidney in critically ill patients with AKI and acute respiratory distress syndrome (ARDS) and global implications of AKI. We discuss disease-specific molecular mediators and inflammatory pathways involved in organ crosstalk in the AKI-ARDS construct, and highlight the reciprocal hemodynamic effects of elevated pulmonary vascular resistance and central venous pressure (CVP) leading to renal hypoperfusion and pulmonary edema associated with fluid overload and increased right ventricular afterload. Finally, we discuss the notion of different ARDS “phenotypes” and the response to fluid overload, suggesting differential organ crosstalk in specific pathological states. While the directionality of effect remains challenging to distinguish at the bedside due to lag in diagnosis with conventional renal function markers and lack of tangible damage markers, this review provides a paradigm for understanding kidney-lung interactions in the critically ill patient.

The many faces and outcomes of pulmonary vein stenosis in early childhood.

Pulmonary vein stenosis is a rare and poorly understood condition causing obstruction of the large pulmonary veins and of blood flow from the lungs to the left atrium. This results in elevated pulmonary venous pressure and pulmonary edema, pulmonary hypertension, potentially cardiac failure, and death. Clinical signs of the disease include failure to thrive, increasingly severe dyspnea, hemoptysis, respiratory difficulty, recurrent respiratory tract infections/pneumonia, cyanosis, and subcostal retractions. On chest radiograph, the most frequent finding is increased interstitial, ground-glass and/or reticular opacity. Transthoracic echocardiography with pulsed Doppler delineates the stenosis, magnetic resonance imaging and multislice computerized tomography are used for further evaluation. Interventional cardiac catherization, surgical techniques, and medical therapies have been used with varying success as treatment options.

Predictors of Complications During Percutaneous Multitrack Balloon Mitral Valvuloplasty

Introduction: Mitral Stenosis (MS) is characterized by a decrease in Mitral Valve (MV) orifice area leading to compromised left ventricular filling. The consequence is stagnation of blood proximal to the MV that results in elevated left atrial, pulmonary venous, and pulmonary artery pressure. Aim of the work: Trace the complication of mitral regurgitation during the procedure percutaneous Balloon Mitral Valvuloplasty (PMV) by using multitrack balloon. Subjects and methods: This interventional non-randomized cohort study was conducted on 121 patients who presented with moderate to severe MS and subjected to PMV using multitrack balloon technique and were divided into 2 groups, according to resultant mitral regurgitation: Group A: included patients with no or mild mitral regurgitation and Group B: included patients with severe mitral regurgitation. Results: Multivariate regression identified MV balloon sizing (OR 3.877, CI 95% 1.131-13.289, P value 0.031), MV commissural asymmetry (OR 67.48, CI 95% 5.759-790.72, P value 0.001). Conclusion: Mitral valve calcification, balloon sizing and MV asymmetry are significant factors that can predict the development of severe MR after balloon valvuloplasty.

Pulmonary hypertensive crisis in children with idiopathic pulmonary arterial hypertension undergoing cardiac catheterization: the risk factors and clinical aspects

Objective: To investigate the risk factors, clinical features, treatments, and prevention of pulmonary hypertensive crisis (PHC) in children with idiopathic pulmonary arterial hypertension (IPAH) undergoing cardiac catheterization. Methods: This retrospective study included 67 children who were diagnosed with IPAH and underwent cardiac catheterization between April 2009 and June 2017 in Beijing Anzhen Hospital. The medical histories, clinical manifestations, treatments, and outcomes were characterized. Statistical analyses were performed using t test, χ(2) test and a multiple Logistic regression analysis. Results: During cardiac catheterization, five children developed PHC who presented with markedly elevated pulmonary artery pressure and central venous pressure, decline in systemic arterial pressure and oxygen saturation. Heart rate decreased in 4 cases and increased in the remaining one. After the treatments including cardiopulmonary resuscitation, pulmonary vasodilator therapy, improving cardiac output and blood pressure, and correction of acidosis, 4 of the 5 cases recovered, while 1 died of severe right heart failure with irreversible PHC 3 days after operation. Potential PHC was considered in 7 other patients, whose pulmonary artery pressure increased and exceeded systemic arterial pressure, oxygen saturation decreased, and central venous pressure and vital signs were relatively stable. Univariate analysis showed that the risk factors of PHC in children with IPAH undergoing cardiac catheterization were younger age (t=3.160, P=0.004), low weight (t=4.004, P<0.001), general anesthesia (χ(2)=4.970, P=0.026), history of syncope (χ(2)=4.948, P=0.026), and WHO cardiac functional class Ⅲ or Ⅳ (χ(2)=19.013, P<0.001). Multivariate Logistic regression analysis revealed that worse WHO cardiac functional class (Wald=13.128, P<0.001, OR=15.076, 95% CI: 3.475-65.418) was the independent risk factor of PHC. Conclusions: PHC is a severe and extremely dangerous complication in children with IPAH during cardiac catheterization. WHO cardiac functional class may be associated with PHC. Integrated treatment is required for these patients. Reducing risk factors, early identification, and active treatment may help to prevent the occurrence and progression of PHC.

Right Heart Pressure Transients and Pulmonary Venous Pressure

tricular (RV) ejection phase indices were limited in part because the complex shape and geometry of the right ventricle limited any reasonable calculation of volume and wall stress. Likewise, methods to assess the RV ejection fraction were in their infancy. By contrast, RV and pulmonary artery (PA) pressure measurements were relatively easy to obtain and it was thought that RV pressure transients and the isovolumic indices of contractility might be applied to the assessment of RV and perhaps even global cardiac contractility. This idea matured during deliberations about the independent function of the right ventricle and the fact that RV failure occurring secondary to LV failure was not easily explained on the basis of the relatively small pressure load imposed by elevated pulmonary venous pressures. Recognizing the distinct architectural and anatomic differences between the right and left ventricles, further discussions led to considerations of ventricular interaction and the possibility that the normal left ventricle directly assists the right ventricle in its pumping function while the dysfunctional left ventricle was limited in this regard. In the early 1970s, cardiologists exhibited a considerable interest in the relative merits of the isovolumic and ejection phase indices of left ventricular (LV) contractility. The isovolumic indices were derived from high-fidelity measurements of LV pressure prior to aortic valve opening; thus, LV pressure and the time derivative of pressure (dP/dt) were used to calculate ‘contractile element’ velocity during the early systole when ventricular volume was nearly constant. Because the pressure transients occurred prior to aortic valve opening, the isovolumic indices were considered to be independent of changes in aortic pressure and LV afterload. The ejection phase indices were derived from measurements of LV dimensions or volume during ejection; thus, dimension or volume strain (ejection fraction) and strain rates were determined. With the incorporation of pressure data, wall stresses were calculated, myocardial length-force-shortening relations were plotted, and afterload-ejection fraction assessed [1–4] . During this period, interest in the right ventricle was limited, mainly due to technical reasons. The right venReceived: April 28, 2016 Accepted after revision: May 9, 2016 Published online: June 10, 2016

Pulmonary Aspects of Exercise and Sports.

Although the lungs are a critical component of exercise performance, their response to exercise and other environmental stresses is often overlooked when evaluating pulmonary performance during high workloads. Exercise can produce capillary leakage, particularly when left atrial pressure increases related to left ventricular (LV) systolic or diastolic failure. Diastolic LV dysfunction that results in elevated left atrial pressure during exercise is particularly likely to result in pulmonary edema and capillary hemorrhage. Data from race horses, endurance athletes, and triathletes support the concept that the lungs can react to exercise and immersion stress with pulmonary edema and pulmonary hemorrhage. Immersion in water by swimmers and divers can also increase stress on pulmonary capillaries and result in pulmonary edema. Swimming-induced pulmonary edema and immersion pulmonary edema in scuba divers are well-documented events caused by the fluid shifts that occur with immersion, elevated pulmonary venous pressure during extreme exercise, and negative alveolar pressure due to inhalation resistance. Prevention strategies include avoiding extreme exercise, avoiding over hydration, and assuring that inspiratory resistance is minimized.

EVALUATION OF PULMONARY GLUCOSE METABOLISM WITH FDG-PET/CT IN PATIENTS WITH PULMONARY ARTERY HYPERTENSION AND PULMONARY HYPERTENSION DUE TO LEFT HEART DISEASE

Pulmonary arterial hypertension (PAH; WHO group 1) is a progressive disease characterized by profound vascular remodeling of the media with proliferation of smooth muscle cells in pulmonary arteries and arterioles. In contrast, pulmonary hypertension (PH) associated with left heart disease (WHO group 2) is caused largely by passive transmission of elevated pulmonary venous pressures into the lung arterial system. Recent studies showed increased glucose metabolism in the lung parenchyma in animal models or small PAH patient cohorts, and may reflect underlying metabolic abnormalities in the remodeled pulmonary vasculature. However, there is no study to compare lung FDG uptake in patients with PAH with those with PH due to left heart disease (group 2 PH), in which the same metabolic abnormalities may not be evident. The aim of this study was to compare lung FDG uptake among three groups including PAH groups, group 2 PH and control subjects. Twenty-two patients with PAH (13 patients with idiopathic PAH and 9 patients with connective tissue disease), 8 patients with group 2 PH, as well as 14 control subjects (no lung disease, no uncontrolled diabetes or PH) were included. There were no significant differences in the mean age between cohorts (PAH 55.6±14.0 vs control 55.9±17.1 vs group 2 PH 59.4±14.5 yrs, p=0.83). Mean pulmonary arterial pressure (mPAP) was assessed with right heart catheterization and was not significantly different between PAH and group 2 PH (45.0±12.1 vs 42.1 mmHg, p=0.56). All subjects underwent FDG-PET/CT imaging. Regions of interest (ROIs) were drawn manually to include the lateral one-third of the lungs on the sagittal images to avoid including obvious pulmonary vessels or non-specific fibrosis. The mean standard uptake value (SUV g/cc) of FDG in each lung was obtained and average values of both lungs were calculated as mean lung FDG SUV. The correlation between mPAP and mean lung FDG SUV was also analyzed in PAH and group 2 PH. PAH patients demonstrated significantly increased mean lung FDG SUV compared with control subjects and group 2 PH (PAH: 0.79±0.27 vs control: 0.53±0.19 vs group 2 PH: 0.35±0.20, p<0.0001). The mean lung FDG SUV did not correlate with mPAP either in PAH or group 2 PH. PAH is associated with increased pulmonary FDG uptake indicating increased glucose metabolism in the lung. This may represent active inflammation and requires further study.

The hemodynamic basis of exercise intolerance in tricuspid regurgitation.

Patients with severe tricuspid regurgitation (TR) frequently present with exertional fatigue and dyspnea, but the hemodynamic basis for exercise limitation in people with TR remains unclear. Twelve subjects with normal left ventricular (LV) ejection fraction and grade ≥3 TR underwent high-fidelity invasive hemodynamic exercise testing with simultaneous expired gas analysis and were compared with 13 age- and sex-matched controls. At rest, TR subjects had lower pulmonary blood flow (3.6±0.4 versus 5.1±1.9 L/min; P=0.01), increased right atrial pressure (12±5 versus 4±1 mm Hg; P=0.0002), and higher pulmonary capillary wedge pressure (17±5 versus 9±3 mm Hg; P=0.0001). However, LV transmural pressure (pulmonary capillary wedge pressure-right atrial pressure), which reflects LV preload independent of right heart congestion and pericardial restraint, was similar in TR and controls (6±3 versus 4±2 mm Hg; P=0.3). With exercise, TR subjects displayed lower peak VO2 (10.3±2.8 versus 13.8±4.2 mL/min per kg; P=0.02), lower pulmonary blood flow (6.4±1.3 versus 10.3±3.3 L/min; P=0.001), and less increase in pulmonary blood flow relative to VO2 (+4.6±1.1vs +6.2±0.7; P=0.001). TR subjects displayed higher pulmonary capillary wedge pressure with exercise, but this was solely because of RA hypertension (27±9 versus 8±3 mm Hg; P<0.0001), because LV transmural pressure dropped with exercise in subjects with TR (-5±6 versus +3±3 mm Hg; P=0.0007), suggesting inadequate LV diastolic filling, despite high pulmonary capillary wedge pressure. Impaired exercise capacity in people with severe TR is related to low cardiac output reserve relative to metabolic needs, coupled with elevated systemic and pulmonary venous pressures. Left heart pressures are elevated with exercise in subjects with TR, despite low LV preload, secondary to enhanced ventricular interaction.

Pulmonary Vascular Hemodynamic Response to Exercise in Cardiopulmonary Diseases

Pulmonary hypertension (PH), regardless of the pathobiology and site of functional changes, is characterized by an asymptomatic or a latent phase followed by a gradual reduction in exercise capacity related to decreasing right ventricular (RV) contractile reserve.1,2 In addition to right heart and pulmonary vascular function, other factors including ventilation/perfusion mismatch, hypoxemia, peripheral oxygen transportation/utilization, and impaired skeletal muscle function, may significantly influence the functional status of patients with PH.3 Guidelines provide a clinical classification system that categorizes PH into 5 groups with specific pathogenesis, pathologies, and clinical characteristics.1,2 The natural history of the disease is determined by the rapidity of increase in resting mean pulmonary artery pressure (mPAP) and the ability of the RV to compensate and hypertrophy, which differs depending on the pathobiology and related diseases.1,2 The definition of PH and PH groups is based on clinical assessment and invasive hemodynamics. Precapillary PH (groups 1 and 3–5) is characterized as a resting mPAP of ≥25 mm Hg and pulmonary capillary wedge pressure (PCWP) or left ventricular (LV) end-diastolic pressure ≤15 mm Hg. Postcapillary PH (group 2) is associated with an elevated pulmonary venous pressure (>15 mm Hg) related to left heart disease, which may involve abnormalities of the LV, mitral valve, or aortic valve.2 Although the group definitions for PH are helpful, in clinical practice, it is not uncommon for patients to have >1 disease associated with PH and to have both precapillary and postcapillary components, so called multifactorial PH (eg, aortic stenosis, systemic sclerosis, chronic thromboembolic disease) or out-of-proportion PH for a given condition (eg, chronic lung disease, chronic heart failure). The concept that symptoms associated with cardiopulmonary diseases would be associated with an abnormal increase in mPAP with exercise was …

Right Ventricular Strain in Pulmonary Hypertension

Since 2009, there have been ≥170 articles published in the cardiopulmonary literature on right ventricular (RV) echocardiographic strain imaging, including several in Circulation: Cardiovascular Imaging . Of particular interest has been the effort to use RV echocardiographic strain imaging to assess RV systolic function in pulmonary hypertension and the relationship of RV strain to disease severity and outcomes. In this issue of Circulation: Cardiovascular Imaging , Fine et al,1 from the Mayo Clinic echo group, report on retrospectively evaluated data on the relationship of RV strain to outcomes in the largest such study to date, encompassing 575 patients with known or suspected pulmonary hypertension without elevated pulmonary venous pressure during a median follow-up period of 16.5 months.1 The data show a strong association between reductions in mean longitudinal strain and all-cause mortality, and cardiopulmonary mortality and cardiopulmonary events. An exhaustive biostatistical analysis shows the relationship to be quantitative, stronger than that of other echo indices including tricuspid annular plane systolic excursion, independent of clinical covariates and resulting in a significant improvement in predictive value when combined with relevant clinical variables, as reflected in a significant increase in the integrated discrimination improvement index and the c-statistic for the primary end point. Thus, the results promise to improve clinical risk assessment significantly for such patients and may improve clinical decision making. Article see p 711 The apparent benefit is, in large part, a reflection of the relatively weak performance of older 2-dimensional (2D) echocardiographic indices of RV performance including fractional area change and tricuspid annular plane systolic excursion in this setting. RV imaging has been a minefield for echocardiography in adults since its inception. The complexity of ventricular shape, the thinness of the RV free wall, and the limitations in adults of transthoracic and subcostal windows in permitting full visualization …

Pulmonary hypertension in heart failure with preserved left ventricular ejection fraction

To clarify the importance of pulmonary hypertension in the diagnosis and treatment of heart failure with preserved ejection fraction (HFpEF). Pulmonary hypertension is frequently present in HFpEF because of both elevated pulmonary venous pressure and some element of pulmonary vasoconstriction. HFpEF may be the most common cause of pulmonary hypertension in the elderly. The noninvasive detection of pulmonary hypertension can distinguish patients with HFpEF from those with diastolic dysfunction without heart failure. Pulmonary hypertension may be an important target for treatment of HFpEF. Phosphodiesterase-5 inhibitors are a promising method to treat pulmonary hypertension because of HFpEF. Pulmonary hypertension is an important contributor to the pathophysiology of HFpEF, can be used to recognize HFpEF and may be an important target for therapy.

Severe Pulmonary Hypertension: The Role of Metabolic and Endocrine Disorders

Pulmonary arterial hypertension (PAH) is a multi-factorial condition and the underlying pulmonary vascular disease is shaped by the combined action of genetic, epigenetic and immune-related factors. Whether and how gender, obesity and the metabolic syndrome modify PAH and associated right heart failure is under intense investigation. Estrogens may enhance the process of pulmonary angioproliferation, but may also protect the right ventricle under pressure. Obesity may affect the pulmonary circulation via interactions with inflammatory cells and mediators, or via alterations in endocrine signaling. Obesity is a major risk factor for pulmonary hypertension in patients with elevated pulmonary venous pressure and preserved LV ejection fraction. Given the overlap between PAH and autoimmune diseases, hypothyroidism in patients with PAH is commonly considered a consequence of an autoimmune thyroiditis. In the clinical setting of hyperthyroidism, severe pulmonary hypertension may develop due to a hyperdynamic circulation, but a more complex situation presents itself when hyperthyroidism is associated with PAH. We recently showed in a relevant animal model of severe PAH that thyroid hormone, via its endothelial cell-proliferative action, can be permissive and drive angioproliferation. Signaling via the integrin αvβ3 and FGF receptors may participate in the formation of the lung vascular lesions in this model of PAH. Whether thyroid hormones in euthyroid PAH patients play a pathobiologically important role is unknown- as we also do not know whether the commonly diagnosed hypothyroidism in patients with severe PAH is cardioprotective. This brief review highlights some recent insights into the role of metabolic and endocrine disorders in PAH.

Prevalence and Risk Factors of Pulmonary Hypertension in Patients With Elevated Pulmonary Venous Pressure and Preserved Ejection Fraction

Pulmonary hypertension (PH) is a well-recognized complication of left-sided heart failure with preserved left ventricular systolic function that portends a worse prognosis. The identification of risk factors may provide insight into possible mechanisms for the development of PH in this population. Targeting these risk factors could possibly attenuate the development of PH. The limited data available regarding the prevalence of PH and its risk factors in patients with heart failure with preserved left ventricular systolic function are based on echocardiography. To further study this, an institutional database was searched for all patients who underwent right-sided and left-sided cardiac catheterization with ventriculography from October 1996 to September 2007 who met the following criteria: left ventricular end-diastolic pressure (LVEDP) >15 mm Hg, a left ventricular ejection fraction > or =50%, and no significant left-sided cardiac valvular disease. The demographic, clinical, and hemodynamic data of these patients were then analyzed. Of 455 patients who met these criteria, 239 (52.5%) had PH, defined as mean pulmonary artery pressure >25 mm Hg. Using multivariate logistic regression, PH was strongly and independently associated with LVEDP > or =25 mm Hg (odds ratio 4.3), morbid obesity (odds ratio 3.4), and atrial arrhythmias (odds ratio 3.1). Other significant associations were age > or =80 years, chronic obstructive pulmonary disease, and dyspnea on exertion. In conclusion, PH is a frequent finding in patients with elevated LVEDPs and preserved left ventricular systolic function. Factors associated with its development are LVEDP > or =25 mm Hg, morbid obesity, atrial arrhythmias, age > or =80 years, chronic obstructive pulmonary disease, and dyspnea on exertion.

Nursing Considerations for Children Undergoing Delayed Sternal Closure After Surgery for Congenital Heart Disease

Nursing Considerations for Children Undergoing Delayed Sternal Closure After Surgery for Congenital Heart Disease

Left Ventricular Response to Mitral Regurgitation

Mitral regurgitation (MR) burdens the left ventricle with a volume load that leads to a series of left ventricular (LV) compensatory adaptations and adjustments that vary considerably during the prolonged clinical course of MR.1–4 The early compensatory changes observed in acute MR (ie, utilization of the Frank-Starling mechanism) are gradually replaced by a chronic remodeling process with enlargement of the LV chamber. Eventually, these compensatory adaptations fail, LV dysfunction develops, and transition to a decompensated phase of chronic MR occurs (Table). In the present report, the LV response to MR will be described, the evolution from a compensated to a decompensated state will be discussed, and the therapeutic implications of these events will be considered. Published guidelines provide detailed recommendations for the evaluation and treatment of patients with MR, including those with a variety of comorbidities.5,6 The present review is limited to a discussion of the changes in LV size and function that develop as a result of degenerative disease of the mitral valve (recognized clinically as severe mitral valve prolapse with or without partial flail leaflet) or, less commonly, rheumatic mitral valve disease. Our primary goal is to review the rationale for the use of measurements of LV size and function as guides to the management of patients with MR. View this table: Table. LV Structure and Function in the 3 Stages of Chronic MR The clinical impact of MR is determined by the magnitude of the regurgitant leak (ie, the regurgitant volume) and the time course of development of the regurgitation. Patients with the abrupt onset of severe MR generally present with markedly elevated pulmonary venous pressure, whereas those with chronic MR exhibit prominent ventricular enlargement with increased chamber compliance and lower pulmonary venous pressure.2,7 In this section, the determinants of regurgitant flow will be defined and the …

Diagnosis and Treatment of Secondary (Non–Category 1) Pulmonary Hypertension

Pulmonary hypertension occurs commonly in cardiopulmonary disease. In 1998, a new clinical classification was proposed that divided pulmonary hypertension into 5 categories on the basis of the presumed underlying etiology of the pulmonary vascular disease1 (Table 1). Although it was never intended that this classification be used as a guideline to determine appropriate therapy, somewhat surprisingly, the regulatory authorities decided that all medications that were clinically tested and approved for patients with idiopathic pulmonary arterial hypertension (PAH) and patients with pulmonary hypertension associated with connective tissue diseases be applied to all category 1 patients.2 The wisdom of this can be debated at a later date. However, it has left clinicians somewhat confused about the utilization of therapies to treat patients who fall outside of category 1 pulmonary hypertension, often referred to as secondary pulmonary hypertension. View this table: Table 1. Current Clinical Classification of Pulmonary Hypertension 1 There are 3 classes of approved therapies for PAH, all of which are considered to be pulmonary vasodilators: endothelin receptor blockers, phosphodiesterase-5 inhibitors, and prostacyclins.3 Their clinical efficacy has been based on a short-term improvement in exercise tolerance, as measured by a 6-minute walk test. In all of the clinical trials, an improvement in walk was apparent within the first 4 weeks of use, allowing a judgment about efficacy to be made quickly.4 Hemodynamically, their effects are modest, but they tend to raise cardiac output with little effect on pulmonary artery pressure. This has important implications when they are considered for unapproved use. We review the distinctive features of these causes of pulmonary hypertension and the data on the evidence that supports or refutes the use of these therapies in non–category 1 pulmonary hypertension. Patients with pulmonary venous hypertension have elevated pulmonary venous pressure (as reflected in the pulmonary capillary wedge pressure), …

Tadalafil: the evidence for its clinical potential in the treatment of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH), characterized by increased pulmonary artery pressures in the absence of elevated pulmonary venous pressures, is a progressive disease associated with reduced exercise capacity and increased mortality risk. Current treatments for PAH include nonspecific vasodilators, prostacyclin and related analogs, and endothelin receptor antagonists. Since phosphodiesterase type 5 is highly expressed in pulmonary vascular tissues, agents that selectively inhibit phosphodiesterase type 5 activity induce pulmonary arterial vasodilatation, and are being developed for the treatment of PAH. The purpose of this review is to evaluate the existing evidence for the use of tadalafil, a selective phosphodiesterase type 5 inhibitor, in PAH. Data from erectile dysfunction populations indicate that tadalafil is well tolerated with an elimination half-life of 17.5 hours. Small pilot studies in patients with PAH of mixed etiology demonstrate that tadalafil reduces pulmonary vascular resistance and is associated with improved clinical status. A multicenter, randomized, placebo-controlled clinical trial in patients with PAH is currently recruiting patients. Based on existing studies of sildenafil, a related selective phosphodiesterase type 5 inhibitor in PAH, and the findings of initial pilot studies, tadalafil appears to have excellent potential to provide therapeutic benefit in patients with pulmonary hypertension. The long elimination half-life of tadalafil makes it suitable for once-daily dosing.