Left-sided Heart Disease Research Articles

Update on tricuspid regurgitation

Although commonly detected by transthoracic echocardiography, tricuspid regurgitation (TR) has been somehow neglected, and recent data have emerged on the need for careful examination of the tricuspid valve. Functional or secondary TR is the most frequent etiology of tricuspid valve pathology in western countries and is related to tricuspid annular dilation and leaflet tethering. The prognostic role of TR associated with organic left-sided valvular heart disease is well known. However, the value of functional TR in outcome stratification of patients with advanced left ventricular dysfunction is less clear. Surgical tricuspid repair has been avoided for years, because of the misconception that TR should disappear once the primary left-sided problem is treated; this results in a large number of untreated patients with functional TR. Over the past few years, many investigators have reported evidence in favor of a more aggressive surgical approach to functional TR. Consequently, interest has been growing in the pathophysiology and treatment of functional TR. The purpose of this article is to provide a comprehensive review of TR incorporating a description of valve anatomy, etiological factors, pathophysiology, epidemiological data, natural history, clinical evaluation, along with a discussion of the important role in prognostic stratification and a summary of management guidelines.

Doppler echocardiographic evidence of pulmonary hypertension in dogs: a retrospective clinical investigation

Pulmonary hypertension (PH) decreases resistance to fatigue and life expectancy. The aim of this study was to correlate some indirect Doppler indices of PH with tricuspid and pulmonary regurgitation criteria and to relate PH on different indices with the severity of clinical signs. Furthermore the pathogenetic mechanisms associated to PH development were discussed. Dogs with Doppler echocardiographic evidence of PH diagnosed by assessment of pulmonary and tricuspid regurgitant jet velocity were selected, their clinical records were reviewed and a clinical score was computed. Seventeen cases of PH were identified. The degree of PH was assessed based on systolic or diastolic pulmonary pressure and the indirect Doppler indices (AT/ET and Tei Index) were calculated; data were statistically evaluated. Indirect Doppler indices were calculated also in a control group of seven healthy dogs. The most common clinical signs were coughing, dyspnea and syncope; the most common condition associated to PH development was the left-sided valvular heart disease. A significant positive correlation was found between Tei Index and both the systolic pressure and the severity of PH while no correlations were found between PH on different indices and clinical score and/or severity of clinical signs. Results of this study suggest that Tei-index could be an useful support not only to reveal PH but also to give information on the severity of PH. The clinical picture in dogs with PH is apparently unpredictable and not strictly correlated with the severity of PH.

Assessment of Right Ventricular Function by Tissue Doppler, Strain and Strain Rate Imaging in Patients with Left-Sided Valvular Heart Disease and Pulmonary Hypertension

Background: Pulmonary artery hypertension is the presentation of various types of cardiovascular and systematic diseases. There are different kinds of noninvasive methods to determine right ventricular function, pulmonary artery pressure, and effect of pulmonary hypertension on right ventricular function. These methods include the tissue Doppler imaging (TDI) of the tricuspid annulus and the longitudinal deformation indices of the right ventricular free wall. Objectives: In some patients, the echocardiogram cannot help estimate pulmonary artery pressure. In this study, we evaluated the effect of pulmonary hypertension on the TDI of the tricuspid annulus and the longitudinal strain and strain rate of the basal segment of the right ventricular free wall in patients with left-sided valvular heart disease and pulmonary hypertension. Indeed, we sought to investigate whether we can guess the presence of pulmonary hypertension through the measurement of the TDI of the tricuspid annulus and the deformity indices of the basal segment of the right ventricular free wall. Patients and Methods: Eighty consecutive patients with left-sided valvular disease and pulmonary artery hypertension (V/PH Group) and 80 healthy matched controls (H Group) were enrolled in this research. The TDI parameters were obtained in the tissue velocity imaging mode during systole (S, S VTI), early relaxation (E), atrial systole (A), and isovolemic relaxation time (IVRT). The deformation indices included peak systolic longitudinal strain and strain rate measured from the basal segment of the right ventricular free wall and were calculated as the relative magnitude of segmental deformation. Results: S, E, and S VTI were reduced significantly in the V/PH Group, and there was a significant negative correlation between S velocity, S VTI with pulmonary artery systolic pressure (PASP), and right ventricular diameter (RVD). According to the ROC curve, S velocity 40 ms had 78% sensitivity and 67% specificity for the prediction of pulmonary hypertension. In comparison with the H Group, RV longitudinal peak systolic strain (-14/35 ± 4%) and strain rate (-0.65 ± 0.12) at the basal segment of the right ventricular free wall were significantly lower in the V/PH Group (P < 0.001 and P < 0.001). Conclusions: We observed a significant reduction in S, E velocity, and S VTI of the tricuspid annulus. Moreover, the strain/strain rate of the basal segment of the right ventricular free wall had a marked decrease in the V/PH Group in comparison with the healthy subjects.

Prognostic Value of Pulmonary Hypertension in Ambulatory Patients With Non-Ischemic Dilated Cardiomyopathy

Pulmonary hypertension (PH) because of left-sided heart disease carries a poor prognosis. We investigated whether non-ischemic dilated cardiomyopathy (DCM) with PH is associated with poor prognosis. A total of 256 consecutive DCM patients were enrolled. We measured the ratio of the maximum first derivative of left ventricular pressure (LVdP/dtmax)/systolic blood pressure and pressure half-time (T1/2) as cardiac function. Patients were allocated to 2 groups on the basis of mean pulmonary arterial pressure (mPAP), namely DCM without PH group (mPAP <25 mmHg; n=225) and DCM with PH group (mPAP ≥25 mmHg; n=31). We followed all patients for a mean of 4.3 years for the occurrence of cardiac events, defined as cardiac death or hospitalization for worsening heart failure. Cardiac events were significantly more frequent in the DCM with PH group than in the DCM without PH group (P<0.001). Multivariate Cox regression analysis revealed that mPAP ≥25 mmHg and LV end-systolic volume index were significant independent risk factors for cardiac death. Incidence of cardiac death was significantly higher in patients with DCM with PH than in those without PH [hazard ratio 11.79 (3.18-43.7), P<0.0001]. The presence of PH was independently associated with an increased incidence of cardiac death in ambulatory patients with DCM.

Pharmacological management of pulmonary arterial hypertension.

Pharmacological management of pulmonary arterial hypertension.

Pulmonary Hypertension in Systemic Lupus Erythematosus

Pulmonary hypertension (PH) is a life-threatening complication of systemic lupus erythematosus (SLE). Pulmonary hypertension in SLE has a variety of causes. Diagnosing early and defining the cause of PH accurately can provide better clinical outcome in SLE. We investigated the causes and characteristics of PH in patients with SLE. One hundred twenty-one patients with SLE who had a visit in a 6-month period were assessed retrospectively. Patients who ever had a systolic pulmonary arterial pressure of 40 mm Hg or greater by Doppler echocardiography were considered to have PH. Among 122 patients, 65 had echocardiography for some reason, and 10 (8.2%) were diagnosed as having PH by echocardiographic examination. This number reduced to 9 (7.4%) when we excluded the patient with normal pulmonary artery pressure at right heart catheterization. Causes of PH were as follows: thromboembolic events in 4 patients (44.4%) (2 of them had chronic thromboembolic PH), left-sided heart disease in 2 patients (22.2%), pulmonary arterial hypertension in 1 patient (11.1%), high cardiac output state in 1 patient (11.1%), and transient elevation of systolic pulmonary artery pressure in 1 patient (11.1%) who had a history of venous thromboembolism. Venous thromboembolic disease was significantly higher in patients with SLE with PH in comparison to patients with SLE without PH (7 patients [6.3%] vs 5 patients [50.0%]; P = 0.001). All patients improved clinically during their short-term follow-up. Patients with SLE are at increased risk for PH. This study highlights the complexity of the differential diagnosis of PH in patients with SLE once again and emphasizes the importance of pulmonary thromboembolism as a cause of PH. One should investigate patients with SLE with unexplained symptoms and/or signs related to PH for possible treatable causes.

Independent Prognostic Value of Right Atrial Pressure in Patients with Congestive Heart Disease

When significant pulmonary hypertension (PH) develops in association with left-sided heart disease (LHD), it leads to poor prognosis. Up to the present, mean pulmonary arterial pressure (mPAP) and right ventricular (RV) ejection fraction are reported as a predictor of survival. We sought a better understanding of the hemodynamic parameters in the patients with pulmonary arterial wedge pressure (PCW) ≥ 15 mmHg. It might improve the accuracy of the prognostic stratification of patients with congestive heart failure.

Pulmonary Arterial Hypertension Associated with Connective Tissue Disease

Pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) is a disease of excessive mortality compared to other etiologies of PAH. It makes difficult to treat patients with CTD-PAH that they often have multiple etiologies of pulmonary hypertension (PH) such as pulmonary venous hypertension secondary to left-side heart disease, PH due to interstitial lung disease (ILD) and chronic thromboembolic pulmonary hypertension. Thus, in the treatment of CTD-PH, it is important to accurately differentiate its cause at first.

Reproducibility and correlations of right ventricular end‐diastolic volume index measured by real‐time three‐dimensional echocardiography

To correlate right ventricular volumes measured by real-time three-dimensional echocardiography (RT3DE) with left ventricular volume indices in patients with or without left-sided heart diseases. For this retrospective, we reviewed 806 consecutive RT3DE examinations with quantitative evaluation of both the left and the right (RV) ventricle. We excluded cases of disease or surgery that would directly affect the size of the RV (eg, intracardiac shunt, significant tricuspid, or pulmonic regurgitation) as well as poor sonographic image quality, leaving a total of 701 studies for analysis. RV volumetric quantification was performed using dedicated software. Linear regression analysis showed that left ventricular stroke volume index significantly correlated with RV end-diastolic volume index (RVEDVI) (r = 0.78, p < 0.0001). Overall, 4% (28 of 701) of the patients had RVEDVI lower than 50 ml/m(2) , and 12% (84 of 701) had RVEDVI greater than 100 ml/m(2) . Intraclass correlation coefficient ranged from 0.91 to 0.99 for intraobserver and 0.85 to 0.98 for interobserver reproducibility. RT3DE was feasible and reproducible for quantifying RV volume. In patients without known primary RV pathology, RV volume strongly correlated with left ventricular stroke volume.

Sleeping and resting respiratory rates in dogs with subclinical heart disease

To characterize sleeping respiratory rates (SRRs) and resting respiratory rates (RRRs), collected in the home environment, of dogs with subclinical heart disease that could result in left-sided congestive heart failure. Prospective cross-sectional study. 190 adult dogs with subclinical left-sided heart disease. Most dogs had mitral valve disease or dilated cardiomyopathy of various severities. Clients collected ten 1-minute SRRs or RRRs during a period ranging from 1 week to 6 months. Clinicians provided echocardiographic and medical data on each patient. The within-dog mean SRR (SRRmean; 16 breaths/min) was significantly lower than the within-dog mean RRR (RRRmean; 21 breaths/min). Seven dogs had SRRmean and 33 dogs had RRRmean > 25 breaths/min; 1 dog had SRRmean and 12 dogs had RRRmean > 30 breaths/min; these dogs mostly had a left atrial (LA)-to-aortic ratio > 1.8. Dogs with moderate LA enlargement had a significantly higher SRRmean than did other dogs. However, median SRRmean for each of 4 levels of LA enlargement was < 20 breaths/min; median RRRmean for each of 4 levels of LA enlargement was < 25 breaths/min. Both within-dog SRR and RRR remained stable for 10 consecutive measurements. Treatment with cardiac medications or presence of pulmonary hypertension was not associated with SRRmean or RRRmean. Results suggested that dogs with confirmed subclinical left-sided heart disease of various severities generally had SRRmean < 25 breaths/min, which was infrequently exceeded at any time, and that SRR and RRR remained stable, regardless of individual within-dog SRRmean or RRRmean.

Lapatinib impact on pulmonary hypertension.

160 Background: Pulmonary Arterial Hypertension (PAH) and cancer share growth factor and protein kinase signaling pathways that result in smooth muscle cell proliferation and vasculopathy. A number of tyrosine kinase inhibitors (TKI) have been developed for the treatment of cancer, and some of these like Imatinib have been investigated in PAH. There is little known about the impact of other TKI on the pulmonary vasculature. After reporting a case of lapatinib-induced PAH that reversed after withdrawal of the drug, we investigated the association of lapatinib with the development of PAH in our institution. Methods: A retrospective chart review was conducted, in accordance with IRB protocol, of all patients treated with lapatinib over the past five years at our institution. Patients who had undergone 2-D echocardiogram both prior to and after treatment were included in the analysis. Systolic Pulmonary Artery Pressures (PASP), right-sided chamber dilation and function, TAPSE were each evaluated. Through chart review, patients were evaluated in terms of risk factors for non-Group 1 PAH. A Wilcoxon signed-rank sum test was used to compare the changes in PASP before and after the initiation of lapatinib. Results: A total of 27 patients were found to have 2-D echo done before and after starting treatment with lapatinib. All patients had normal PASP before starting treatment. Eight patients developed elevated PASP following treatment. Two patients had evidence of left-sided heart disease felt to contribute to their elevated pressures, while the remaining 6 patients had no evidence for Group 2 (associated with left heart disease), 3 (associated with lung disease or hypoxemia) or chronic thromboembolic PAH. Right heart catheterization was available in one patient, confirming the diagnosis of PAH. The median pre-treatment and post treatment PASP in those 6 patients was 29.5 mmHg and 65.5 mmHg respectively (N=6; p = 0.03). Conclusions: Lapatinib is a TKI with a selective inhibition to EGFR and HER2, approved by FDA in 2007 as a second line agent in advanced breast cancer. Given the potential of TKIs as anti-proliferative agents in PAH, a number are currently under study, but little is yet known. This is the first study in the literature to show that PAH is a potential side effect of lapatinib.

Benefits of multimodality imaging for pulmonary venous anatomy evaluation

A 41-year-old man evaluated for recurrent blackouts was found to have dilated right heart chambers with signs of right ventricular volume overload. There were no valvular abnormalities, intracardiac shunts, or left-sided heart disease noted with transthoracic echocardiography. Transoesophageal echocardiography (TEE) confirmed a sinus venosus atrial septal defect (ASD) ( Panel A ) associated …

WHO's in Second?

World Health Organization (WHO) group 2 pulmonary hypertension (PH) due to left-side heart disease (ie, heart failure or left-sided valvular heart disease) is the most common form of PH in western countries. Distinguishing patients with WHO group 2 PH, particularly the subset of patients with PH due to heart failure with preserved ejection fraction (HFpEF), from those with WHO group 1 pulmonary arterial hypertension (PAH) is challenging. Separating the two conditions is of vital importance because treatment strategies differ completely. Furthermore, therapies that are indicated for WHO group 1 PAH may be harmful in patients with WHO group 2 PH. We review the somewhat confusing PH nomenclature and the WHO classification system and rationale behind it. We then focus on left-side heart disorders that cause PH. An aging population and advances in the medical management of common cardiovascular disorders have caused the prevalence of heart failure to rise significantly, with more than one-half of patients having HFpEF. We review contemporary studies that focus on clinical and echocardiographic findings that help to distinguish HFpEF from PAH in the patient with PH. We discuss the typical, and sometimes atypical, hemodynamic profiles that characterize these two groups, review challenges in the interpretation of data obtained by right-sided heart catheterization, and highlight special maneuvers that may be required for accurate diagnosis. Finally, we review the largely disappointing studies on the use of PAH-specific therapies in patients with WHO group 2 PH, including the use of prostacyclins, endothelin receptor antagonists, and the more promising phosphodiesterase-5 inhibitors.

Treatment of Pulmonary Hypertension Caused by Left Heart Failure With Pulmonary Arterial Hypertension–Specific Therapies

It has been axiomatic since the early clinical trials with epoprostenol1,2 that drugs having efficacy treating pulmonary arterial hypertension (PAH) have no clear beneficial effects in treating pulmonary hypertension caused by left-sided heart disease and may actually be deleterious. Although dysfunction of the 3 major endothelium-derived pathways targeted by currently approved PAH therapies—the endothelin, nitric oxide, and prostacyclin pathways—is also present in pulmonary hypertension resulting from left-sided heart disease, their role in the pathogenesis of pulmonary vasculopathy in this setting remains unclear. Article see p 502 Riociguat is a novel molecular entity that acts as a soluble guanylate cyclase activator, thereby directly producing vasodilation and stimulating endogenous nitric oxide–mediated vasodilation. Riociguat is currently undergoing regulatory review for the indications of PAH and inoperable chronic thromboembolic pulmonary hypertension on the basis of the Pulmonary Arterial Hypertension sGC-Stimulator Trial and Chronic Thromboembolic Pulmonary Hypertension sGC-Stimulator Trial, respectively.3,4 In these trials, treatment with riociguat improved 6-minute walking distance (the primary end point) and several secondary end points compared with placebo and appeared to be safe and well tolerated. If approved, riociguat would be the first drug approved for inoperable chronic thromboembolic pulmonary hypertension and would join the ranks of other oral therapies for PAH. In this issue of Circulation , Bonderman and colleagues5 report the results of the Left Ventricular Systolic Dysfunction Associated With PH Riociguat Trial (LEPHT), in which they evaluated the effects of riociguat in subjects with pulmonary hypertension caused by left ventricular systolic dysfunction that persisted despite maximal conventional therapy. They enrolled 202 subjects who …

Biomarkers in Pulmonary Hypertension

Pulmonary hypertension (PH) is a hemodynamic condition that has a poor prognosis and can lead to right-sided heart failure. It may result from common diseases such as left-sided heart or lung disease or may present as the rare entity of idiopathic pulmonary arterial hypertension. Biomarkers that specifically indicate the pathologic mechanism, the severity of the disease, and the treatment response would be ideal tools for the management of PH. In this review, markers related to heart failure, inflammation, hemostasis, remodeling, and endothelial cell-smooth muscle cell interaction are discussed, and their limitations are emphasized. Anemia, hypocarbia, elevated uric acid, and C-reactive protein levels are unspecific markers of disease severity. Brain natriuretic peptide and N-terminal fragment of pro-brain natriuretic peptide have been recommended in current guidelines, whereas other prognostic markers, such as growth differentiation factor-15, osteopontin, and red cell distribution width, are emerging. Chemokines of the CC family and matrix metalloproteases have been linked to the vascular pathologic mechanisms, and new markers such as apelin have been described. Circulating endothelial and progenitor cells have received much attention as markers of disease activity, but with controversial findings. A lack of standards for cell isolation and characterization methods and differences in the pathologic mechanisms of the investigated patients may have contributed to the discrepancies. In conclusion, although several promising markers have been identified over the past few years, the development of more specific markers, standardization, and prospective validation are warranted.

SAT0192 High Frequency of Left-Sided Heart Diseases as an Important Cause of Pulmonary Hypertension in Connective Tissue Diseases

BackgroundPulmonary hypertension (PH) is one of the fatal complications in the connective tissue disease (CTD).(1) CTD-associated pulmonary hypertension (CTD-PH) is sometimes associated with left heart disease and interstitial lung disease...

AB0404 Association between arterial stiffness and pulmonary arterial hypertension in systemic lupus erythematosus

BackgroundAlthogh pulmonary arterial hypertension (PAH) is a severe manifestation of systemic lupus erythematosus (SLE), the pathogenesis of PAH associated with SLE is yet unclear.ObjectivesIn this study, we evaluated the carotid...

CT Scanning in the Evaluation of Pulmonary Hypertension

Right-heart catheterization is currently the gold standard method for detecting pulmonary hypertension (PH) and grading its severity. Our study determined the utility of computerized tomography (CT) scans for detecting PH in patients with left-sided heart disease, thereby potentially avoiding the overuse of invasive right-heart catheterization. A retrospective review was conducted on 40 patients with left-sided cardiac pathology who had undergone both right-heart catheterization and CT scanning of the chest. Mean pulmonary artery diameters (MPADs) were measured on CT scans and compared with pulmonary artery pressures measured by right-heart catheterization. Patients with mild-to-moderate PH had significantly greater CT-measured MPADs (34.89 ± 1.01) than patients without PH (controls) (27.36 ± 0.83, p < 0.001). Patients with severe PH had significantly greater MPADs (38.31 ± 0.88) than both mild-to-moderate PH patients (p < 0.01) and controls (p < 0.001). Receiver operating characteristic curve analysis showed that CT scanning predicted PH with an area under the curve of 0.95 (p < 0.0001). A cutoff MPAD of >33.3 mm had 100% specificity and 100% positive predictive value (N = 40, p < 0.0001), and a cutoff MPAD of <27.3 mm had 100% sensitivity with 100% negative predictive value (N = 40, p < 0.001). CT scanning correctly identified all patients with PH with MPADs >34 mm and excluded all patients without PH when MPADs were <27 mm. We advocate that the measurement of MPAD by CT scanning can be quickly and easily performed by the clinician to screen for the presence of PH.

Pulmonary Hypertension

In the Clinic7 May 2013Pulmonary HypertensionJess Mandel, MD, David Poch, MD, Deborah Cotton, MD, MPH, Darren B. Taichman, MD, PhD, and Sankey V. Williams, MDJess Mandel, MDSearch for more papers by this author, David Poch, MDSearch for more papers by this author, Deborah Cotton, MD, MPHSearch for more papers by this author, Darren B. Taichman, MD, PhDSearch for more papers by this author, and Sankey V. Williams, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-9-201305070-01005 SectionsSupplemental MaterialAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The pulmonary vascular bed is normally a low-resistance, high-capacitance circuit capable of accommodating the entire cardiac output at pressures approximately 15%–20% of those in the systemic circulation. In pulmonary hypertension (PH), elevated pulmonary arterial pressure places a burden on the normally thin-walled right ventricle as it works to maintain normal blood flow. Without effective therapy, right heart dysfunction leads to progressive symptoms and is often fatal. Pulmonary hypertension is frequently a result of common left-sided heart or lung diseases. Less frequently, it results from a disease process intrinsic to the pulmonary vasculature itself. Differentiating among the several causes of PH ...

Left ventricular dysfunction with pulmonary hypertension: part 2: prognosis, noninvasive evaluation, treatment, and future research.

Pulmonary hypertension (PH) secondary to left-sided heart disease (Group 2 PH) is a frequent complication of heart failure (HF) that worsens exercise capacity, risk for hospitalization, and survival independent of left-ventricular ejection fraction (LVEF) or stage of HF. Increased pulmonary artery pressure (PAP) in patients with HF often represents a combination of increased left-sided filling pressures (passive component) and elevated pulmonary vascular resistance (PVR) attributable to functional and structural abnormalities of the pulmonary vascular bed (reactive component). The latter may be reversible with standard HF treatment in the earlier stages, when remodeling of the pulmonary vasculature has not set in, and abnormalities in pulmonary arterial tone are the major driver for elevated PVR. However, chronic exposure to elevated pulmonary capillary wedge pressure (PCWP) may lead to permanent changes in the pulmonary arterial bed (irreversible or fixed PH).1 Considering that a number of drug classes have successfully modified the natural history of pulmonary arterial hypertension (Group 1 PH) and demonstrated that intervention is possible even after pulmonary vascular remodeling has occurred,2 Group 2 PH is a natural target for screening and potential intervention in patients with HF. In the second part of this 2-part review, we discuss the prognostic impact of PH in HF, the contemporary diagnostic and evaluation approaches, the current evidence from clinical studies in Group 2 PH, the challenges of appropriate patient selection in clinical trials, and potential ways to overcome these challenges in trial designs. ### Echocardiographic Studies Studies using either right heart catheterization (RHC) or echocardiography for determination of PAP have consistently shown that PH considerably worsens prognosis in HF. Abramson et al3 first reported that tricuspid regurgitation jet velocity >2.5 m/s was associated with 3.4 times higher mortality in 108 patients with dilated cardiomyopathy followed for up to 28 months; hospitalization rate for HF was …