Clinical application of tissue Doppler imaging in patients with idiopathic pulmonary hypertension

BACKGROUND: Tissue Doppler (TD) echocardiographic imaging of mitral and tricuspid annulus has been applied to assess right ventricular (RV) and left ventricular (LV) function in many cardiac diseases, but its clinical application, including response to long-term targeted therapy in patients with idiopathic pulmonary hypertension (PH), has not been addressed. METHODS: Seventy patients with idiopathic PH were compared with 35 age-matched control subjects to examine myocardial velocities by TD. Of these, 35 patients underwent repeat imaging after long-term targeted therapy. In addition, 50 consecutive patients with idiopathic PH with simultaneous right-heart catheterization and echocardiography were examined. RESULTS: No significant differences were noted between PH patients and the control group in lateral mitral annulus systolic velocity and early diastolic velocity (Ea) by TD, but septal velocities were significantly lower (p < 0.01). With targeted therapy, myocardial velocities at the septum and RV free wall increased significantly (p < 0.05). Likewise, E/Ea ratio increased, albeit still in the normal range. In all 50 patients with invasive measurements, lateral E/Ea ratio readily identified normal mean pulmonary capillary wedge pressure (PCWP). CONCLUSIONS: TD imaging of the lateral mitral annulus can reliably predict the presence of normal/reduced mean PCWP in patients with idiopathic PH, and track the improvement in RV function and LV filling with long-term targeted therapy.     

Chronic and acute effects of smoking on left and right ventricular relaxation in young healthy smokers

BACKGROUND: Left ventricular (LV) diastolic dysfunction has been observed in cigarette smokers with coronary artery disease. The aim of the study was to assess LV and right ventricular (RV) diastolic function in healthy, young, and slim smokers before and after smoking one cigarette. MATERIAL AND METHODS: The participants were 66 healthy volunteers (age < 40 years; body mass index < 25 kg/m(2)): 33 smokers (study group [HS]) and 33 nonsmokers (control group). Echocardiographic examination was done in the HS before smoking one cigarette (HS-1) and after smoking one cigarette (HS-2). To assess diastolic function of LV and RV mitral valve flow (MVF), pulmonary venous flow (PVF) and tricuspid valve flow (TVF) were evaluated. RESULTS: MVF early to late phase ratio (E/A) was significantly lower in HS-1 and HS-2 than in the control group. The PVF systolic to diastolic phase ratio (S/D) was significantly higher in HS-1 and HS-2 than in the control group. These changes suggest LV diastolic function impairment in the HS, but the MVF pattern remained within the normal range. PVF S/D showed systolic dominance (S/D > 1) typical for impaired LV relaxation and abnormal for this age group. TVF E/A was significantly lower in HS-2 than in HS-1 and control subjects and suggests RV diastolic dysfunction. CONCLUSIONS: The following conclusion are made: (1) MVF and PVF demonstrate LV relaxation impairment in healthy smokers before and after smoking one cigarette; (2) the assessment of PVF is a good method reflecting LV diastolic function changes, even when MVF remains normal; and (3) TVF shows RV relaxation impairment after smoking one cigarette in healthy smokers.     

Prognostic Value of RV Function Before and After Lung Transplantation

ObjectivesWe investigated the effects of lung transplantation on right ventricular (RV) function as well as the prognostic value of pre- and post-transplantation RV function.BackgroundAlthough lung transplantation success has improved over recent decades, outcomes remain a challenge. Identifying predictors of mortality in lung transplant recipients may lead to improved long-term outcomes after lung transplantation.MethodsEighty-nine (age 60 ± 6 years, 58 men) consecutive patients who underwent single or double lung transplantation and had pre- and post-transplantation echocardiograms between July 2001 and August 2012 were evaluated. Echocardiographic measurements were performed before and after lung transplantation. Left ventricular (LV) and RV longitudinal strains were analyzed using velocity vector imaging. Cox proportional prognostic hazard models predicting all-cause death were built.ResultsThere were 46 all-cause (52%) and 17 cardiac (19%) deaths during 43 ± 33 months of follow-up. After lung transplantation, echocardiography showed improved systolic pulmonary artery pressure (SPAP) (50 ± 19 mm Hg to 40 ± 13 mm Hg) and RV strain (−17 ± 5% to −18 ± 4%). No pre-transplantation RV parameter predicted all-cause mortality. After adjustment for age, sex, surgery type, and etiology of lung disease in a Cox proportional hazards model, both post-transplantation RV strain (hazard ratio: 1.13, 95% confidence interval: 1.04 to 1.23, p = 0.005), and post-transplantation SPAP (hazard ratio: 1.03, 95% confidence interval: 1.01 to 1.05, p = 0.011) were independent predictors of all-cause mortality. When post-transplantation RV strain and post-transplantation SPAP were added the clinical predictive model based on age, sex, surgery type, and etiology, the C-statistic improves from 0.60 to 0.80 (p = 0.002).ConclusionsAlterations of RV function and pulmonary artery pressure normalize, and post-transplantation RV function may provide prognostic data in patients after lung transplantation. Our study is based on a highly and retrospectively selected group. We believe that larger prospective studies are warranted to confirm this result.     

Reduced intrathoracic blood volume and left and right ventricular dimensions in patients with severe emphysema: an MRI study

BACKGROUND: Left ventricular (LV) filling is impaired in patients with severe emphysema manifesting in small end-diastolic dimensions. We hypothesized that the hyperinflated lungs of these patients with high intrinsic positive end-expiratory pressure will decrease intrathoracic blood volume (ITBV) and ventricular preload. We therefore measured ITBV, and LV and right ventricular (RV) dimensions and function using MRI techniques in patients with severe emphysema. METHODS: Patients with severe emphysema (n = 13) and matched healthy volunteers (n = 11) were included. The magnetic resonance (MR) examination consisted of three parts: (1) evaluation of RV and LV dimensions and function and interventricular septum curvature using cine MRI; (2) quantification of aortic flow using MR phase velocity mapping; and (3) calculation of the cardiopulmonary peak transit time (PTT) from the pulmonary artery to the ascending aorta using contrast-enhanced, time-resolved, two-dimensional MR angiography. RESULTS: There were no differences between the groups regarding age, height, or weight. In the emphysema patients, ITBV index (- 35%), LV end-diastolic volume index (LVEDVI) [- 21%], RV end-diastolic volume index (- 20%), cardiac index (- 22%), and stroke volume index (SVI) [- 40%] were lower compared to control subjects. LV and RV end-systolic volumes, LV wall mass, septal curvature, and PTT did not differ between the groups. LVEDVI (r = 0.83) as well as SVI (r = 0.82) correlated closely to ITBV index. SVI correlated closely to LVEDVI (r = 0.84). CONCLUSIONS: LV and RV performance is impaired in patients with severe emphysema because of small end-diastolic dimensions. One possible explanation for the decreased biventricular preload in these patients is intrathoracic hypovolemia caused by hyperinflated lungs.     

Early changes of cardiac structure and function in COPD patients with mild hypoxemia

BACKGROUND: COPD is often associated with changes of the structure and the function of the heart. Although functional abnormalities of the right ventricle (RV) have been well described in COPD patients with severe hypoxemia, little is known about these changes in patients with normoxia and mild hypoxemia. STUDY OBJECTIVES: To assess the structural and functional cardiac changes in COPD patients with normal Pa(O2) and without signs of RV failure. METHODS: In 25 clinically stable COPD patients (FEV1, 1.23 +/- 0.51 L/s; Pa(O2), 82 +/- 10 mm Hg [mean +/- SD]) and 26 age-matched control subjects, the RV and left ventricular (LV) structure and function were measured by MRI. Pulmonary artery pressure (PAP) was estimated from right pulmonary artery distensibility. RESULTS: RV mass divided by RV end-diastolic volume as a measure of RV adaptation was 0.72 +/- 0.18 g/mL in the COPD group and 0.41 +/- 0.09 g/mL in the control group (p < 0.01). LV and RV ejection fractions were 62 +/- 14% and 53 +/- 12% in the COPD patients, and 68 +/- 11% and 53 +/- 7% in the control subjects, respectively. PAP estimated from right pulmonary artery distensibility was not elevated in the COPD group. CONCLUSION: From these results, we conclude that concentric RV hypertrophy is the earliest sign of RV pressure overload in patients with COPD. This structural adaptation of the heart does not alter RV and LV systolic function.     

Thalassemia heart disease: a comparative evaluation of thalassemia major and thalassemia intermedia

BACKGROUND: Heart disease represents the main determinant of survival in beta-thalassemia, but its particular features in the two clinical forms of the disease, thalassemia major (TM) and thalassemia intermedia (TI), are not completely clarified. METHODS: We compared clinical and echocardiographic global parameters in 131 TM patients who received regular chelation transfusions and were highly compliant with treatment (mean age, 28 +/- 6 years [+/- SD]), and 74 age-matched, TI patients who did not receive chelation transfusions. RESULTS: Congestive heart failure was encountered in five patients with TM (3.8%; age range, 25 to 29 years) and in two patients with TI (2.7%; age range, 37 to 40 years). Systolic left ventricular (LV) dysfunction (ejection fraction < 55% or shortening fraction < 35%) was only encountered in patients with TM (8.4%). Considerable pulmonary hypertension (systolic tricuspid gradient > 35 mm Hg) was only present in TI (23.0%). In the remaining patients without evident heart disease, cardiac dimensions, LV mass, LV shortening and ejection fractions, and cardiac output were significantly higher in patients with TI. LV afterload was higher in patients with TM. LV diastolic early transmitral diastolic peak flow velocity (E)/late transmitral diastolic peak flow velocity (A) ratio was also higher in TM. Systolic and mean pulmonary artery pressures and total pulmonary resistance were higher in both young and old TI patients. CONCLUSION: Regular lifelong transfusion and chelation therapy in TM prevented premature heart disease and pulmonary hypertension, although LV dysfunction still occurred and led to heart failure. The absence of regular therapy in TI, in contrast, preserved systolic LV function but allowed pulmonary hypertension development, which also led to heart failure, starting within the fourth decade of life, a decade later compared to TM.     

Atrial septostomy in treatment of end-stage right heart failure in patients with pulmonary hypertension

BACKGROUND: Right ventricular (RV) failure is the main cause of death in patients with pulmonary hypertension (PH). Balloon atrial septostomy (BAS) is believed to relieve symptoms of PH by increasing systemic flow and reducing RV preload. METHODS: Fourteen BAS procedures were performed in 11 patients (5 men and 6 women; mean [+/- SD] age, 33 +/- 12 years) with RV failure in the course of PH that was refractory to conventional treatment. BAS consisted of a puncture of the interatrial septum and subsequent dilatations with balloons of increasing diameter in a step-by-step manner. RESULTS: After BAS, the mean oxygen saturation of aortic blood decreased (before, 93 +/- 4%; after, 84 +/- 4%; p = 0.001), while mean cardiac index increased (before, 1.54 +/- 0.34 L/min/m(2); after, 1.78 +/- 0.35 L/min/m(2); p = 0.001), resulting in a positive trend for mean systemic oxygen transport (before, 270 +/- 64 mL/min; after, 286 +/- 81 mL/min; p = 0.08). Pulmonary vascular resistance (PVR) slightly increased immediately after the procedure, and this rise inversely correlated with mixed venous blood partial oxygen pressure both before BAS (r = -0.69; p = 0.009) and after BAS (r = -0.64; p = 0.018). Mean functional class improved from 3.2 +/- 0.4 to 2.6 +/- 0.7 (p = 0.03) after 1 month. At follow-up (mean time to follow-up, 8.1 +/- 6.2 months; range, 0.8 to 20.2 months), seven patients died and two underwent lung transplantation. There was no difference in the survival rate compared to that obtained from National Institutes of Health equation. A significant size reduction in the created defect was observed in six patients, requiring repeat BAS procedures in three cases. CONCLUSIONS: The current BAS technique improves cardiac index and functional class without significant periprocedural complications, except for a transient increase in PVR related to acute desaturation of mixed venous blood. At long-term follow-up, a high incidence of spontaneous decrease in orifice size has been observed.     

Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure

BACKGROUND: Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. METHODS: We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. RESULTS: One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). CONCLUSIONS: There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.     

Hemodynamic effects of sildenafil in patients with congestive heart failure and pulmonary hypertension: combined administration with inhaled nitric oxide

STUDY OBJECTIVES: In patients with pulmonary hypertension (PH) secondary to congestive heart failure, inhaled nitric oxide (NO) increases pulmonary vascular smooth-muscle intracellular cyclic guanosine monophosphate (cGMP) concentration, thereby decreasing pulmonary vascular resistance (PVR) and increasing cardiac index (CI). However, these beneficial effects of inhaled NO are limited in magnitude and duration, at least in part due to cGMP hydrolysis by the type 5 isoform of phosphodiesterase (PDE5). The goal of this study was to determine the acute pulmonary and systemic hemodynamic effects of the selective PDE5 inhibitor, sildenafil, administered alone or in combination with inhaled NO in patients with congestive heart failure and PH. DESIGN: Single center, case series, pharmacohemodynamic study. SETTING: Cardiac catheterization laboratory of a tertiary care academic teaching hospital. PATIENTS: We studied 11 patients with left ventricular systolic dysfunction due to coronary artery disease or idiopathic dilated cardiomyopathy who had PH. INTERVENTIONS: We administered oral sildenafil (50 mg), inhaled NO (80 ppm), and the combination of sildenafil and inhaled NO during right-heart and micromanometer left-heart catheterization. MEASUREMENTS AND RESULTS: Sildenafil administered alone decreased mean pulmonary artery pressure by 12 +/- 5%, PVR by 12 +/- 5%, systemic vascular resistance (SVR) by 13 +/- 6%, and pulmonary capillary wedge pressure by 12 +/- 7%, and increased CI by 14 +/- 5% (all p < 0.05) [+/- SEM]. The combination of inhaled NO and sildenafil decreased PVR by 50 +/- 4%, decreased SVR by 24 +/- 3%, and increased CI by 30 +/- 4% (all p < 0.01). These effects were greater than those observed with either agent alone (p < 0.05). In addition, sildenafil prolonged the pulmonary vasodilator effect of inhaled NO. Administration of sildenafil alone or in combination with inhaled NO did not change systemic arterial pressure or indexes of myocardial systolic or diastolic function. CONCLUSIONS: PDE5 inhibition with sildenafil improves cardiac output by balanced pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled NO in patients with chronic congestive heart failure and PH.     

Left ventricular diastolic dysfunction in patients with COPD in the presence and absence of elevated pulmonary arterial pressure

BACKGROUND: Increased right ventricular afterload leads to left ventricular diastolic dysfunction due to ventricular interdependence. Increased right ventricular afterload is frequently present in patients with COPD. The purpose of this study was to determine whether left ventricular diastolic dysfunction could be detected in COPD patients with normal or elevated pulmonary artery pressure (PAP). METHODS: Twenty-two patients with COPD and 22 matched control subjects underwent pulsed Doppler echocardiography. Left ventricular systolic dysfunction and other causes of left ventricular diastolic dysfunction (eg, coronary artery disease) were excluded in all patients and control subjects. PAP was measured invasively in 13 patients with COPD. RESULTS: The maximal atrial filling velocity was increased and the early filling velocity was decreased in patients with COPD compared to control subjects. The early flow velocity peak/late flow velocity peak (E/A) ratio was markedly decreased in patients with COPD compared to control subjects (0.79 +/- 0.035 vs 1.38 +/- 0.069, respectively; p < 0.0001), indicating the presence of left ventricular diastolic dysfunction. The atrial contribution to total left diastolic filling was increased in patients with COPD. This was also observed in COPD patients with normal PAP, as ascertained using a right heart catheter. The atrial contribution to total left diastolic filling was further increased in COPD patients with PAP. PAP correlated with the E/A ratio (r = -0.85; p < 0.0001). CONCLUSIONS: Left ventricular diastolic dysfunction is present in COPD patients with normal PAP and increases with right ventricular afterload.     

Prognostic value of echocardiographic right/left ventricular end-diastolic diameter ratio in patients with acute pulmonary embolism: results from a monocenter registry of 1,416 patients

BACKGROUND: In the literature, echocardiographic assessment of the prognosis of acute pulmonary embolism is based on analysis of right ventricle free-wall motion or on a composite index combining right ventricular dilatation, paradoxical septal wall motion, and pulmonary hypertension. The aim of this study was to determine the prognostic value of a single quantitative echocardiographic criterion, the right/left ventricular end-diastolic diameter (RV/LV) ratio. METHODS: Registry data on 1,416 consecutive patients hospitalized for acute pulmonary embolism were used to study retrospectively a population of 950 patients who underwent echocardiographic assessment on hospital admission and for whom the RV/LV ratio was available. RESULTS: The hospital mortality rate for the series was 3.3%. Sensitivity and specificity of RV/LV ratio >or= 0.9 for predicting hospital mortality were 72% and 58%, respectively. Multivariate analysis showed the independent predictive factors for hospital mortality to be the following: systolic BP < 90 mm Hg (odds ratio [OR], 10.73; p < 0.0001), history of left heart failure (OR, 8.99; p < 0.0001), and RV/LV ratio >or= 0.9 (OR, 2.66; p = 0.01). CONCLUSIONS: In our retrospective series, an echocardiographic RV/LV ratio >or= 0.9 was shown to be an independent predictive factor for hospital mortality. This criterion may be of value in selecting cases of submassive pulmonary embolism with a poor prognosis that are liable to benefit from thrombolytic treatment.     

Bone marrow-derived cells contribute to pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension

STUDY OBJECTIVE: In these days, it was reported that bone marrow (BM) cells might take part in the remodeling of some systemic vascular diseases; however, it remains unknown whether the BM cells were involved in the vascular remodeling of pulmonary arteries and the progression of pulmonary hypertension (PH). The purpose of this study was to investigate whether BM-derived cells contribute to pulmonary vascular remodeling in hypoxia-induced PH. MATERIALS AND METHODS: To investigate the role of BM-derived cells, we transplanted the whole BM of enhanced green fluorescent protein (GFP)-transgenic mice to the lethally irradiated syngeneic mice (n = 30). After 8 weeks, chimera mice were exposed to consistent hypoxia using a hypoxic chamber (10% O(2)) for up to 4 or 8 weeks (10 mice per group). After hemodynamics and the ratio of right ventricular (RV) weight to left ventricle (LV) weight, RV/(LV + septum [S]), were measured, histologic and immunofluorescent staining were performed. RESULTS: BM-transplanted mice showed a high chimerism (mean [+/- SEM], 91 +/- 2.3%). RV systolic pressure and the RV/(LV + S) ratio increased significantly with time in PH mice, indicating RV hypertrophy. Marked vascular remodeling including medial hypertrophy and adventitial proliferation was observed in the pulmonary arteries of PH mice. Strikingly, a number of GFP(+) cells were observed at the pulmonary arterial wall, including the adventitia, in hypoxia-induced PH mice, while very few cells were observed in the control mice. Metaspectrometer measurements using confocal laser scanning microscopy confirmed that this green fluorescence was produced by GFP, suggesting that these GFP(+) cells were mobilized from the BM. Most of them expressed alpha-smooth muscle actin, a smooth muscle cell, or myofibroblast phenotype, and contributed to the pulmonary vascular remodeling. A semiquantitative polymerase chain reaction of the GFP gene revealed that the BM-derived GFP-positive cells in the PH group were observed more than eightfold as often compared with the control mice. CONCLUSION: The BM-derived cells mobilize to the hypertensive pulmonary arteries and contribute to the pulmonary vascular remodeling in hypoxia-induced PH mice.     

Unexplained pulmonary hypertension in elderly patients

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) preferentially affects young women. However, a subset of patients with IPAH is elderly. Our objective was to compare elderly (age >/= 65 years) vs younger persons with unexplained pulmonary hypertension (PH) and a presumptive diagnosis of IPAH. METHODS: Clinical, echocardiographic, hemodynamic, and survival data were collected on consecutive patients with suspected IPAH after evaluation in a large tertiary center PH clinic. RESULTS: Of 197 patients (mean age +/- SD, 52 +/- 16 years; 80% female), 48 patients (24%) were elderly. Elderly and younger patients had similar symptom severity, systolic pulmonary artery (PA) pressure (82.7 +/- 20.3 mm Hg vs 86.9 +/- 18.8 mm Hg, respectively; p = 0.21), and severity of right ventricular enlargement and dysfunction. Elderly patients had higher pulmonary capillary wedge pressure (PCWP) [15.3 +/- 7.3 mm Hg vs 11.1 +/- 5.3 mm Hg; p < 0.0001] and more frequently failed (56%) to meet hemodynamic criteria for IPAH (PH with PCWP < 15 mm Hg) than did younger patients (19%). Elderly patients also had higher systemic systolic (p < 0.0001) and pulse (p < 0.0001) pressures and more cardiovascular disease. Among those patients with normal PCWP, elderly patients had worse survival than young patients (p = 0.007). Among those patients with elevated PCWP, elderly patients had lower PA pressures (p = 0.04) and better survival (p = 0.02). CONCLUSIONS: Elderly patients with clinically suspected IPAH often fail to meet hemodynamic criteria for IPAH due to elevated PCWP. Studies to define the proper diagnostic strategy and the safety and efficacy of pulmonary vasodilators in elderly patients with unexplained PH are needed.     

Atrial Remodeling Following Catheter-Based Renal Denervation Occurs in a Blood Pressure– and Heart Rate–Independent Manner

ObjectivesThis study sought to investigate left atrial (LA) remodeling in relation to blood pressure (BP) and heart rate (HR) after renal sympathetic denervation (RDN).BackgroundIn addition to reducing BP and HR in certain patients with hypertension, RDN can decrease left ventricular (LV) mass and ameliorate LV diastolic dysfunction.MethodsBefore and 6 months after RDN, BP, HR, LV mass, left atrial volume index (LAVI), diastolic function (echocardiography), and premature atrial contractions (PAC) (Holter electrocardiogram) were assessed in 66 patients with resistant hypertension.ResultsRDN reduced office BP by 21.6 ± 3.0/10.1 ± 2.0 mm Hg (p < 0.001), and HR by 8.0 ± 1.3 beats/min (p < 0.001). At baseline, LA size correlated with LV mass, diastolic function, and pro-brain natriuretic peptide, but not with BP or HR. Six months after RDN, LAVI was reduced by 4.0 ± 0.7 ml/kg/m² (p < 0.001). LA size decrease was stronger when LAVI at baseline was higher. In contrast, the decrease in LAVI was not dependent on LV mass or diastolic function (E/E′ or E/A) at baseline. Furthermore, LAVI decreased without relation to decrease in systolic BP or HR. Additionally, occurrence of PAC (median of >153 PAC/24 h) was reduced (to 68 PAC/24 h) by RDN, independently of changes in LA size.ConclusionsIn patients with resistant hypertension, LA volume and occurrence of PAC decreased 6 months after RDN. This decrease was independent of BP and HR at baseline or the reduction in BP and HR reached by renal denervation. These data suggest that there is a direct, partly BP-independent effect of RDN on cardiac remodeling and occurrence of premature atrial contractions.     

Depressed myocardial contractile reserve in patients with obstructive sleep apnea assessed by tissue Doppler imaging with dobutamine stress echocardiography

BACKGROUND: Hypoxia has been suggested to affect myocardial contractile function in patients with obstructive sleep apnea (OSA). We sought to determine whether myocardial contractile reserve (MCR), as evaluated by echocardiographic tissue Doppler imaging with dobutamine stress (TDDS), might be depressed in OSA patients. METHODS: Thirty patients with suspected OSA (25 men and 5 women; mean age, 51 +/- 11 years [+/- SD]) underwent overnight polysomnography and TDDS. Peak myocardial systolic velocity (Sm) and peak myocardial early diastolic velocity (Em) in the 12 myocardial segments of the left ventricular (LV) walls were averaged, and the mean Sm and Em during TDDS were compared between patients with apnea-hypopnea index (AHI) <15/h (group 1, n = 13) and those with AHI >/= 15/h (group 2, n = 17). MCR was calculated as the difference between the resting and peak Sm during TDDS. RESULTS: In both groups, Sm increased dose dependently during TDDS. However, the relative increase in Sm was significantly lower in group 2, resulting in a lower value of MCR (5.5 +/- 1.2 cm/s vs 7.4 +/- 1.3 cm/s, p < 0.001). The Em was lower in group 2 compared with group 1 throughout TDDS. MCR was correlated significantly with AHI (r = - 0.67, p < 0.0001), resting Em (r = 0.53, p < 0.005), and body mass index (r = - 0.46, p < 0.05) independent of the LV mass index. CONCLUSIONS: OSA can affect MCR, implying an etiologic contribution from repetitive hypoxic events. TDDS could identify subtle abnormalities of OSA-related cardiac involvement.     

CMR-Verified Diffuse Myocardial Fibrosis Is Associated With Diastolic Dysfunction in HFpEF

ObjectivesThe purpose of this study was to investigate diffuse myocardial fibrosis in patients with systolic heart failure (SHF) and in patients with heart failure with preserved ejection fraction (HFpEF) and the association with diastolic dysfunction of the left ventricle (LV).BackgroundIncreased diffuse myocardial fibrosis may impair LV diastolic function. However, no study has verified the association between the degree of diffuse myocardial fibrosis and the severity of impaired diastolic function in SHF and HFpEF.MethodsForty patients with SHF, 62 patients with HFpEF, and 22 patients without HF underwent cardiac magnetic resonance (CMR), including T1 mapping and cine CMR on a 3-T system. Extracellular volume fraction (ECV), a measure of diffuse myocardial fibrosis, was quantified from T1 mapping. Systolic and diastolic functions of the LV were assessed by cine CMR. The ECV values and LV functional indexes were compared among the 3 groups. Associations between ECV and LV diastolic function were also investigated.ResultsCompared with patients without HF, significantly higher ECV was found in patients with SHF (31.2% [interquartile range (IQR): 29.0% to 34.1%] vs. 27.9% [IQR: 26.2% to 29.4%], p < 0.001) and HFpEF (28.9% [IQR: 27.8% to 31.3%] vs. 27.9% [IQR: 26.2% to 29.4%], p = 0.006). Peak filling rate, a diastolic functional index assessed by cine CMR, was significantly decreased in patients with SHF (1.00 s⁻¹ [IQR: 0.79 to 1.49 s⁻¹] vs. 3.86 s⁻¹ [IQR: 3.34 to 4.48 s⁻¹], p < 0.001) and HFpEF (2.89 s⁻¹ [IQR: 2.13 to 3.50 s⁻¹] vs. 3.86 s⁻¹ [IQR: 3.34 to 4.48 s⁻¹], p < 0.001). Myocardial ECV was significantly correlated with peak filling rate in the HFpEF group (r = −0.385, p = 0.002), but no correlation was found in the SHF and non-HF groups (r = 0.030, p = 0.856 and r = −0.238, p = 0.285, respectively).ConclusionsIn patients with HF, only those with HFpEF show a significant correlation between increased diffuse myocardial fibrosis and impaired diastolic function. Diffuse myocardial fibrosis plays a unique role in the pathogenesis of HFpEF.     

Beneficial effect of bilevel positive airway pressure on left ventricular function in ambulatory patients with idiopathic dilated cardiomyopathy and central sleep apnea-hypopnea: a preliminary study

BACKGROUND: Sleep-disordered breathing is common in individuals with left ventricular (LV) dysfunction and has been treated with nocturnal positive airway pressure. We investigated whether treatment of central sleep apnea-hypopnea with bilevel positive airway pressure (BPAP) in ambulatory patients with idiopathic dilated cardiomyopathy (IDCM) might improve LV function. METHODS: Fifty-two consecutive patients with IDCM who underwent both cardiac catheterization and standard polysomnography were enrolled in the study; individuals with obstructive sleep apnea syndrome were excluded. Subjects with an apnea-hypopnea index (AHI) >or= 20 episodes per hour were randomized to receive medical therapy either alone (n = 11) or together with BPAP (n = 10). RESULTS: LV end-diastolic pressure, pulmonary capillary wedge pressure, and plasma concentration of brain natriuretic peptide were significantly greater, and LV ejection fraction (LVEF) was significantly lower in patients with an AHI >or= 20/h (n = 21, 40.4%) than in those with an AHI < 20/h (n = 31, 59.6%). LVEF (30.5 +/- 1.6% vs 50.8 +/- 3.5%, p < 0.001) [mean +/- SE] and plasma concentration of brain natriuretic peptide (162.8 +/- 44.5 pg/mL vs 32.7 +/- 17.6 pg/mL, p = 0.02) were significantly increased and decreased, respectively, after treatment with BPAP (daily use, 4.8 +/- 0.3 h) for 3 months, whereas these parameters remained unchanged in the control subjects. CONCLUSIONS: Our findings suggest that treatment of coexisting central sleep apnea-hypopnea with BPAP improves LV function in ambulatory patients with IDCM. BPAP should thus be considered as a nonpharmacologic adjunct to conventional drug therapy in such patients.     

Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation

STUDY OBJECTIVES: To assess the pulmonary hemodynamic characteristics in COPD candidates for lung volume reduction surgery (LVRS) or lung transplantation (LT). DESIGN: Retrospective study. SETTING: One center in France. PATIENTS: Two hundred fifteen patients with severe COPD who underwent right-heart catheterization before LVRS or LT. RESULTS: Mean age was 54.6 years. Pulmonary function test results were as follows: FEV(1), 24.3% predicted; total lung capacity, 128.3% predicted; residual volume, 259.7% predicted. Mean pulmonary artery pressure (PAPm) was 26.9 mm Hg. Pulmonary hypertension (PAPm > 25 mm Hg) was present in 50.2% and was moderate (PAPm, 35 to 45 mm Hg) or severe (PAPm > 45 mm Hg) in 9.8% and in 3.7% of patients, respectively. Cardiac index was low normal. PAPm was related to Pao(2) and alveolar-arterial oxygen gradient in multivariate analysis. Cluster analysis identified a subgroup of atypical patients (n = 16, 7.4%) characterized by moderate impairment of the pulmonary mechanics (mean FEV(1), 48.5%) contrasting with high level of pulmonary artery pressure (PAPm, 39.8 mm Hg), and severe hypoxemia (mean Pao(2), 46.2 mm Hg). CONCLUSION: While pulmonary hypertension is observed in half of the COPD patients with advanced disease, moderate-to-severe pulmonary hypertension is not a rare event in these patients. We individualized a subgroup of patients presenting with a predominant vascular disease that could potentially benefit from vasodilators.     

Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodeling

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and hypertension are independently associated with increased stiffness of large arteries that may contribute to left ventricular (LV) remodeling. We sought to investigate the impact of OSA, hypertension, and their association with arterial stiffness and heart structure. DESIGN: We studied 60 middle-aged subjects classified into four groups according to the absence or presence of severe OSA with and without hypertension. All participants were free of other comorbidities. The groups were matched for age, sex, and body mass index. MEASUREMENTS AND RESULTS: Full polysomnography, pulse-wave velocity (PWV), and transthoracic echocardiography were performed in all participants. Compared with normotensive subjects without OSA, PWV, left atrial diameter, interventricular septal thickness, LV posterior wall thickness, LV mass index, and percentage of LV hypertrophy had similar increases in normotensive OSA and patients with hypertension and no OSA (p < 0.05 for all comparisons), with a significant further increase in PWV, LV mass index, and percentage of LV hypertrophy in subjects with OSA and hypertension. Multivariate regression analysis showed that PWV was associated with systolic BP (p < 0.001) and apnea-hypopnea index (p = 0.002). The only independent variable associated with LV mass index was PWV (p < 0.0001). CONCLUSIONS: Severe OSA and hypertension are associated with arterial stiffness and heart structure abnormalities of similar magnitude, with additive effects when both conditions coexist. Increased large arterial stiffness contributes to ventricular afterload and may help to explain heart remodeling in both OSA and hypertension.