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 ≥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 ≥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 ≥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 ≥25 mm Hg, morbid obesity, atrial arrhythmias, age ≥80 years, chronic obstructive pulmonary disease, and dyspnea on exertion.
Chronically, elevated left ventricular (LV) filling pressures despite preserved LV systolic function can lead to pulmonary venous hypertension and remodeling of the pulmonary arterial vasculature. The presence of pulmonary hypertension (PH) and its severity in chronic heart failure is associated with worse outcomes and mortality. The objectives of this observational study were to identify the prevalence and possible risk factors for PH in patients with elevated LV end-diastolic pressure (LVEDP) and preserved LV systolic function in a large population of patients who underwent clinically indicated right-sided and left-sided cardiac catheterization. We hypothesized that the variation in PH would be largely explained by the degree of pulmonary venous hypertension.
Methods
The Dartmouth Dynamic Registry collects clinical, demographic, and procedural data on all patients who undergo cardiac catheterization at Dartmouth-Hitchcock Medical Center. The database was searched for patients who underwent right-sided and left-sided cardiac catheterization with LVEDPs >15 mm Hg, LV ejection fractions ≥50%, and no clinically significant aortic or mitral valve disease (no more than mild) from October 1996 to September 2007. The indication for heart catheterization was established by the referring cardiologist. Cardiac output was determined by the Fick formula using estimated oxygen consumption. When this was not available, the value determined by thermodilution was used. A mean pulmonary artery (PA) pressure >25 mm Hg was used to divide the patients into PH and non-PH groups. Approval was obtained from the Dartmouth-Hitchcock Center for the Protection of Human Subjects.
Baseline characteristics are expressed as mean ± SD or as percentages ( Table 1 ). Chi-square tests were used to test differences between dichotomous variables, and Student’s t tests were used to test differences between continuous variables. After univariate analysis, multivariate logistic regression was performed to identify those variables independently associated with PH. Continuous variables were converted to discrete ranges for the multivariate analysis. All analyses were performed using Stata version 10.0 (StataCorp LP, College Station, Texas).
| Variable | PH | p Value | |
|---|---|---|---|
| No (n = 216) | Yes (n = 239) | ||
| Age (years) | 64.5 ± 12.7 | 67.8 ± 11.2 | 0.003 |
| Body mass index (kg/m 2 ) | 30.1 ± 5.9 | 32.7 ± 8.2 | <0.001 |
| Body mass index >30 kg/m 2 | 42.1% | 57.7% | 0.001 |
| Body mass index >40 kg/m 2 | 5.1% | 16.7% | <0.001 |
| Women | 49.1% | 50.2% | 0.809 |
| Smoking | 30.1% | 37.2% | 0.108 |
| Diabetes | 22.2% | 36.4% | 0.001 |
| Hypertension | 58.8% | 67.4% | 0.058 |
| Hypercholesterolemia | 48.6% | 46.0% | 0.581 |
| Peripheral vascular disease | 4.6% | 8.4% | 0.109 |
| Chronic obstructive pulmonary disease | 10.7% | 21.3% | 0.002 |
| Atrial arrhythmia | 7.9% | 22.2% | <0.001 |
| Serum creatinine (mg/dl) | 0.99 ± 0.29 | 1.06 ± 0.67 | 0.133 |
| Stable angina pectoris | 13.0% | 10.5% | 0.406 |
| Acute coronary syndromes | 10.7% | 10.5% | 0.948 |
| Previous coronary intervention | 9.7% | 10.9% | 0.686 |
| Previous coronary bypass | 5.1% | 3.8% | 0.491 |
| Coronary artery disease | 48.6% | 57.7% | 0.051 |
| 3-vessel coronary disease | 18.1% | 17.6% | 0.893 |
| Cardiogenic shock | 0.5% | 1.3% | 0.366 |
| Heart failure | 14.4% | 28.5% | <0.001 |
| History of ejection fraction <35% | 1.4% | 2.5% | 0.391 |
| Dyspnea on exertion | 50.0% | 70.3% | <0.001 |
| Chest pain | 34.7% | 35.2% | 0.924 |
| Syncope | 5.6% | 3.8% | 0.364 |
| LV systolic pressure (mm Hg) | 155.8 ± 33.6 | 160.6 ± 36.1 | 0.140 |
| LVEDP (mm Hg) | 20.2 ± 4.3 | 22.7 ± 5.8 | <0.001 |
| Right ventricular systolic pressure (mm Hg) | 33.8 ± 6.7 | 50.9 ± 13.5 | <0.001 |
| Right atrial mean pressure (mm Hg) | 7.6 ± 3.6 | 12.8 ± 5.4 | <0.001 |
| Right ventricular end-diastolic pressure (mm Hg) | 10.1 ± 4.1 | 14.9 ± 4.6 | <0.001 |
| Pulmonary artery systolic pressure (mm Hg) | 32.7 ± 6.6 | 51.9 ± 13.2 | <0.001 |
| Pulmonary artery diastolic pressure (mm Hg) | 12.6 ± 4.8 | 22.2 ± 6.8 | <0.001 |
| Pulmonary artery mean pressure (mm Hg) | 20.0 ± 4.1 | 34.2 ± 7.8 | <0.001 |
| Peripheral vascular resistance (dyne · s/cm 5 ) | 54.9 ± 46.5 | 208.5 ± 156.1 | <0.001 |
| Transpulmonary gradient | 3.2 ± 2.4 | 12.4 ± 8.1 | <0.001 |
| Cardiac output (L/min) | 5.6 ± 1.4 | 5.4 ± 1.5 | 0.171 |
| Cardiac index (L/min/m 2 ) | 2.8 ± 0.7 | 2.7 ± 0.7 | 0.107 |
| Estimated ejection fraction (%) | 64.1 ± 7.8 | 61.3 ± 8.6 | <0.001 |
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