Michele D’Alto

Echocardiography in Pulmonary Arterial Hypertension: from Diagnosis to Prognosis

Pulmonary arterial hypertension is most often diagnosed in its advanced stages because of the nonspecific nature of early symptoms and signs. Although clinical assessment is essential when evaluating patients with suspected pulmonary arterial hypertension, echocardiography is a key screening tool in the diagnostic algorithm. It provides an estimate of pulmonary artery pressure, either at rest or during exercise, and is useful in ruling out secondary causes of pulmonary hypertension. In addition, echocardiography is valuable in assessing prognosis and treatment options, monitoring the efficacy of specific therapeutic interventions, and detecting the preclinical stages of disease.

Nonpharmacologic Care of Heart Failure: Patient, Family, and Hospital Organization

Patients with severe heart failure require large quantities of health care resources, and more intensive interventions are not always related to a decrease in need for medical care, including hospitalization. A thoughtful approach to the efficient and expeditious allocation of these resources is required. In fact, the nonpharmacologic therapy of patients with chronic congestive heart failure (CHF) has to include the complete explanation of various topics, such as causes of heart failure, symptoms, diet, salt and fluid restriction, drug regimen, compliance, physical and work activities, lifestyle changes, and measures of self-control. This article describes how the relationship among patient, family, friends, and different heart-care workers (physicians, nurses, psychologists, rehabilitation technicians, dietitians, hospital personnel) can greatly affect therapeutic efficacy.

Repair of Congenital Heart Disease with Associated Pulmonary Hypertension in Children: What are the Minimal Investigative Procedures? Consensus Statement from the Congenital Heart Disease and Pediatric Task Forces, Pulmonary Vascular Research Institute (PVRI)

Standardization of the diagnostic routine for children with congenital heart disease associated with pulmonary arterial hypertension (PAH-CHD) is crucial, in particular since inappropriate assignment to repair of the cardiac lesions (e.g., surgical repair in patients with elevated pulmonary vascular resistance) may be detrimental and associated with poor outcomes. Thus, members of the Congenital Heart Disease and Pediatric Task Forces of the Pulmonary Vascular Research Institute decided to conduct a survey aimed at collecting expert opinion from different institutions in several countries, covering many aspects of the management of PAH-CHD, from clinical recognition to noninvasive and invasive diagnostic procedures and immediate postoperative support. In privileged communities, the vast majority of children with congenital cardiac shunts are now treated early in life, on the basis of noninvasive diagnostic evaluation, and have an uneventful postoperative course, with no residual PAH. However, a small percentage of patients (older at presentation, with extracardiac syndromes or absence of clinical features of increased pulmonary blood flow, thus suggesting elevated pulmonary vascular resistance) remain at a higher risk of complications and unfavorable outcomes. These patients need a more sophisticated diagnostic approach, including invasive procedures. The authors emphasize that decision making regarding operability is based not only on cardiac catheterization data but also on the complete diagnostic picture, which includes the clinical history, physical examination, and all aspects of noninvasive evaluation.

Circulating biomarkers in pulmonary arterial hypertension: Update and future direction

Pulmonary arterial hypertension (PAH) is a complex disease with a poor prognosis. In recent years, great advances have occurred in our understanding of the pathophysiologic mechanisms underlying the characteristic vascular proliferative lesions, thus allowing the development of several specific drugs. Nevertheless, PAH still presents a high mortality; therefore, early diagnosis and prognostic stratification seem to be of paramount importance in order to choose the best therapeutic strategies. Circulating biomarkers have been proposed as potentially noninvasive and objective parameters for diagnosis, prognosis, and response to therapy. The molecules evaluated to date, including markers of dysfunction and neurohormonal activation, myocardial injury, inflammation and oxidative stress, vascular damage and remodelling, end-organ failure, and gene expression, reflect the complex pathophysiology of PAH. However, not one of these shows all the characteristics of the ideal biomarker; thus, a multiparameter approach is probably desirable. Moreover, future direction could be research of structural proteins specifically expressed in the pathologic tissue that act as disease-specific markers. This report presents an extensive review of circulating biomarkers in PAH and some consideration about potential future direction in this area.

Tissue Doppler imaging in systemic sclerosis: A 3-year longitudinal study

OBJECTIVES To investigate by standard echocardiography and pulsed-tissue Doppler imaging (TDI) the course of systemic sclerosis (SSc) heart disease and its correlation with epidemiological, clinical, and serological features of the disease and drug treatment. METHODS A total of 74 consecutive patients (69 females, between the ages of 19 and 71 years, and disease duration 1-43 years) and 71 controls underwent cardiac assessment at baseline and at 3-year follow-up. RESULTS At baseline, compared to controls, patients showed post-Bonferroni correction, impaired left (LV) and right ventricular (RV) diastolic function (Em/Am 0.85 ± 0.4 vs 1.5 ± 0.7, p = 0.0003; Et/At 0.9 ± 0.3 vs 1.3 ± 0.4, p = 0.0003), subtle LV and RV systolic dysfunction (Sm 13.7 ± 2.7 vs 15.4 ± 3.2cm/s, p = 0.031; St < 11.5cm/s in 16/74 patients vs 0 controls, p = 0.0031), and higher pulmonary artery systolic pressure (sPAP) (26.1 ± 6.0 vs 24.1 ± 5.1, p = 0.040). At 3-year follow-up, SSc patients showed a further deterioration of biventricular diastolic and systolic function and a further sPAP increase. At multiple regression analysis of baseline data, Em/Am < 1 was detected in 55/74 patients vs 25/71 controls (p < 0.0001) and was associated with age (p = 0.030); Et/At < 1 was detected in 16/74 patients vs 7/71 controls (p < 0.0001), was associated with NYHA class ≥ II (p = 0.033), late capillaroscopic pattern (p = 0.029), and a baseline cardiac Medsger severity score ≥ 1 (p = 0.029). TDI evidence of new abnormalities in RV and/or LV diastolic function was associated with a baseline cardiac Medsger severity score ≥ 1 (p = 0.01). Neither diastolic or systolic abnormalities nor sPAP changes correlated with treatment. CONCLUSIONS Our study confirms that SSc patients exhibit biventricular systolic and diastolic dysfunction and increased sPAP and reveals further deterioration at 3-year follow-up.

An update on the use of ambrisentan in pulmonary arterial hypertension

The development of effective oral treatments that are capable of modulating the activity of endothelin receptor 1 (ET-1) represents a significant milestone in the field of pulmonary arterial hypertension (PAH). Randomized clinical trials confirm that endothelin receptor antagonist (ERA) treatments confer significant improvements on important clinical endpoints, such as exercise capacity, functional class, quality of life and pulmonary hemodynamics. Moreover, ERAs may prevent or delay clinical worsening and retard disease progression. Ambrisentan is a propanoic acid-based ERA, showing preferential affinity for the type A ET-1 over the type B receptor. It provides another valuable, effective treatment option in PAH. Two large, randomized-placebo controlled trials demonstrated the efficacy of ambrisentan in PAH at improving exercise tolerance as measured by the 6 min walk distance. Additional secondary measures of improvement including time to clinical worsening, survival, functional class, quality of life and hemodynamic variables have been reported in clinical trials. A favorably low incidence of aminotransferase elevation indicating lower hepatic toxicity than other ERAs has been observed. Ambrisentan can be safely administered with warfarin or sildenafil without the need for dose adjustment of either therapy. A once daily oral medication with relatively few side effects is an attractive option, especially as the use of therapies in combination continues to increase. Long-term data and hemodynamic data confirm the benefits can be compared with other ERAs with fewer drug–drug interactions and a better liver safety profile.

Sildenafil in severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A randomized controlled multicenter clinical trial

BACKGROUND Pulmonary hypertension (PH) is a well-known independent prognostic factor in chronic obstructive pulmonary disease (COPD) and a sufficient criterion for lung transplant candidacy. Limited data are currently available on the hemodynamic and clinical effect of phosphodiesterase 5 inhibitors in patients with severe PH associated with COPD. This study assessed the effect of sildenafil on pulmonary hemodynamics and gas exchange in severe PH associated with COPD. METHODS After screening, this multicenter, randomized, placebo-controlled double-blind trial randomized patients to receive 20 mg sildenafil or placebo 3 times a day (ratio 2:1) for 16 weeks. The primary end point was the reduction in pulmonary vascular resistance. Secondary end points included BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, 6-minute walk test, and quality of life questionnaire. Changes in the partial pressure of arterial oxygen were evaluated as a safety parameter. RESULTS The final population included 28 patients, 18 in the sildenafil group and 10 in the placebo group. At 16 week, patients treated with sildenafil had a decrease in pulmonary vascular resistance (mean difference with placebo -1.4 WU; 95% confidence interval, ≤ -0.05; p = 0.04). Sildenafil also improved the BODE index, diffusion capacity of the lung for carbon monoxide percentage, and quality of life. Change from baseline in the partial pressure of arterial oxygen was not significantly different between the sildenafil and placebo groups. CONCLUSIONS This pilot study found that treatment with sildenafil reduced pulmonary vascular resistance and improved the BODE index and quality of life, without a significant effect on gas exchange.

A simple echocardiographic score for the diagnosis of pulmonary vascular disease in heart failure

Aims A simple echocardiographic score was designed for diagnosing precapillary vs postcapillary pulmonary hypertension and for discriminating between isolated postcapillary pulmonary hypertension (Ipc-PH) and combined precapillary and postcapillary pulmonary hypertension (Cpc-PH). Methods The score comprised 7 points (2 for E/e′ ratio ⩽10, 2 for a dilated non-collapsible inferior vena cava, 1 for a left ventricular eccentricity index ≥1.2, 1 for a right-to-left heart chamber dimension ratio >1 and 1 for the right ventricle forming the heart apex) and was applied to 230 consecutive patients referred for evaluation of pulmonary hypertension. Results Precapillary pulmonary hypertension and postcapillary pulmonary hypertension were diagnosed in 160 and 70 patients, respectively. In the latter, Ipc-PH was found in 51 and Cpc-PH in 19. The echo score was higher in precapillary vs postcapillary pulmonary hypertension patients (4.2 ± 1.7 vs 1.6 ± 1.7, P < 0.001) and in patients with Cpc-PH vs Ipc-PH (2.7 ± 2.1 vs 1.2 ± 1.3, P = 0.001). The sensitivity and specificity of the echo score at least 2 for precapillary pulmonary hypertension were 99 and 54%, respectively (area under the curve 0.85). In patients with postcapillary pulmonary hypertension, the sensitivity and specificity of the echo score at least 2 for Cpc-PH were 63 and 82% (area under the curve 0.73). Conclusion A simple echocardiographic score helps in the differential diagnosis between precapillary and postcapillary pulmonary hypertension, and between Ipc-PH and Cpc-PH.

Exercise-Induced Pulmonary Hypertension: Translating Pathophysiological Concepts Into Clinical Practice

&NA; Exercise stress testing of the pulmonary circulation for the diagnosis of latent or early‐stage pulmonary hypertension (PH) is gaining acceptance. There is emerging consensus to define exercise‐induced PH by a mean pulmonary artery pressure > 30 mm Hg at a cardiac output < 10 L/min and a total pulmonary vascular resistance> 3 Wood units at maximum exercise, in the absence of PH at rest. Exercise‐induced PH has been reported in association with a bone morphogenetic receptor‐2 gene mutation, in systemic sclerosis, in left heart conditions, in chronic lung diseases, and in chronic pulmonary thromboembolism. Exercise‐induced PH is a cause of decreased exercise capacity, may precede the development of manifest PH in a proportion of patients, and is associated with a decreased life expectancy. Exercise stress testing of the pulmonary circulation has to be dynamic and rely on measurements of the components of the pulmonary vascular equation during, not after exercise. Noninvasive imaging measurements may be sufficiently accurate in experienced hands, but suffer from lack of precision, so that invasive measurements are required for individual decision‐making. Exercise‐induced PH is caused either by pulmonary vasoconstriction, pulmonary vascular remodeling, or by increased upstream transmission of pulmonary venous pressure. This differential diagnosis is clinical. Left heart disease as a cause of exercise‐induced PH can be further ascertained by a pulmonary artery wedge pressure above or below 20 mm Hg at a cardiac output < 10 L/min or a pulmonary artery wedge pressure‐flow relationship above or below 2 mm Hg/L/min during exercise.

Influence of various therapeutic strategies on right ventricular morphology, function and hemodynamics in pulmonary arterial hypertension

BACKGROUND In idiopathic pulmonary arterial hypertension (IPAH) treatment goals include improving right ventricular (RV) function, hemodynamics and symptoms to move patients to a low-risk category for adverse clinical outcomes. No data are available on the effect of upfront combination therapy on RV improvement as compared with monotherapy. The aim of this study was to evaluate echocardiographic RV morphology and function in patients affected by IPAH and treated with different strategies. METHODS Sixty-nine consecutive, treatment-naive IPAH patients treated with first-line upfront combination therapy at 10 centers were retrospectively evaluated and compared with 2 matched cohorts treated with monotherapy after short-term follow-up. Evaluation included clinical, hemodynamic and echocardiographic parameters. RESULTS At 155 ± 65 days after baseline evaluation, patients in the oral+prostanoid group (Group 1) had the most clinical and hemodynamic improvement compared with the double oral group (Group 2), the oral monotherapy group (Group 3) and the prostanoid monotherapy group (Group 4). The more extensive reduction of pulmonary vascular resistance in Groups 1, 2 and 4 was associated with significant improvement in all RV echocardiographic parameters compared with Group 3. Considering the number of patients who reached the target goals suggested by established guidelines, 8 of 27 (29.6%) and 7 of 42 (16.7%) patients in Groups 1 and 2, respectively, achieved low-risk status, as compared with 2 of 69 (2.8%) and 6 of 27 (22.2%) in Groups 3 and 4, respectively. CONCLUSIONS In advanced treatment-naive IPAH patients, an upfront combination therapy strategy seems to significantly improve hemodynamics and RV morphology and function compared with oral monotherapy. The most significant results seem to be achieved with prostanoids plus oral drug, whereas the use of the double oral combination and prostanoids as monotherapy seem to produce similar results.