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1.
Interact Cardiovasc Thorac Surg ; 15(6): 973-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22997250

ABSTRACT

OBJECTIVES: In chronic thromboembolic pulmonary hypertension (CTEPH), right ventricular (RV) dysfunction is associated with increased morbidity and mortality following pulmonary endarterectomy. Plasma brain natriuretic peptide (BNP) levels were previously shown to correlate with RV (dys)function. We hypothesized that BNP can be used as a non-invasive biomarker to identify patients at 'high risk' for postoperative morbidity and mortality. METHODS: We studied the postoperative outcome in 73 consecutive patients. Patients were divided into three groups based on previously determined cut-off levels: BNP <11.5, indicating normal RV function (ejection fraction [EF] ≥45%), BNP >48.5 pmol/l, indicating RV dysfunction (right ventricular ejection fraction <30%) and BNP 11.5-48.5 pmol/l. Postoperative 'bad outcome' was defined as the presence of either residual pulmonary hypertension (PH) or (all-cause) mortality. RESULTS: Plasma BNP >48.5 pmol/l was shown to be an independent predictor of 'bad outcome'. Compared with BNP <11.5 pmol/l, BNP >48.5 pmol/l identified patients at higher risk for (all-cause) mortality (17 vs 0%; P = 0.009) and residual PH (56 vs 20%; P < 0.004). Also, the durations of mechanical ventilation and intensive care unit stay were significantly longer in patients with BNP >48.5 pmol/ml. CONCLUSIONS: Plasma BNP levels may be of use as a non-invasive biomarker reflecting RV dysfunction, next to other well-recognized (invasive) parameters, for better preoperative risk stratification of CTEPH patients.


Subject(s)
Endarterectomy/mortality , Hemodynamics , Hypertension, Pulmonary/surgery , Natriuretic Peptide, Brain/blood , Pulmonary Embolism/surgery , Adolescent , Adult , Aged , Biomarkers/blood , Endarterectomy/adverse effects , Female , Humans , Hypertension, Pulmonary/blood , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/mortality , Hypertension, Pulmonary/physiopathology , Intensive Care Units , Length of Stay , Logistic Models , Male , Middle Aged , Multivariate Analysis , Pulmonary Embolism/blood , Pulmonary Embolism/complications , Pulmonary Embolism/mortality , Pulmonary Embolism/physiopathology , Respiration, Artificial , Risk Assessment , Risk Factors , Stroke Volume , Time Factors , Treatment Outcome , Up-Regulation , Ventricular Dysfunction, Right/blood , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/physiopathology , Ventricular Function, Right , Young Adult
2.
J Am Coll Cardiol ; 59(24): 2193-202, 2012 Jun 12.
Article in English | MEDLINE | ID: mdl-22676940

ABSTRACT

OBJECTIVES: The purpose of this study was to analyze the electrophysiologic remodeling of the atrophic left ventricle (LV) in right ventricular (RV) failure (RVF) after RV pressure overload. BACKGROUND: The LV in pressure-induced RVF develops dysfunction, reduction in mass, and altered gene expression, due to atrophic remodeling. LV atrophy is associated with electrophysiologic remodeling. METHODS: We conducted epicardial mapping in Langendorff-perfused hearts, patch-clamp studies, gene expression studies, and protein level studies of the LV in rats with pressure-induced RVF (monocrotaline [MCT] injection, n = 25; controls with saline injection, n = 18). We also performed epicardial mapping of the LV in patients with RVF after chronic thromboembolic pulmonary hypertension (CTEPH) (RVF, n = 10; no RVF, n = 16). RESULTS: The LV of rats with MCT-induced RVF exhibited electrophysiologic remodeling: longer action potentials (APs) at 90% repolarization and effective refractory periods (ERPs) (60 ± 1 ms vs. 44 ± 1 ms; p < 0.001), and slower longitudinal conduction velocity (62 ± 2 cm/s vs. 70 ± 1 cm/s; p = 0.003). AP/ERP prolongation agreed with reduced Kcnip2 expression, which encodes the repolarizing potassium channel subunit KChIP2 (0.07 ± 0.01 vs. 0.11 ± 0.02; p < 0.05). Conduction slowing was not explained by impaired impulse formation, as AP maximum upstroke velocity, whole-cell sodium current magnitude/properties, and mRNA levels of Scn5a were unaltered. Instead, impulse transmission in RVF was hampered by reduction in cell length (111.6 ± 0.7 µm vs. 122.0 ± 0.4 µm; p = 0.02) and width (21.9 ± 0.2 µm vs. 25.3 ± 0.3 µm; p = 0.002), and impaired cell-to-cell impulse transmission (24% reduction in Connexin-43 levels). The LV of patients with CTEPH with RVF also exhibited ERP prolongation (306 ± 8 ms vs. 268 ± 5 ms; p = 0.001) and conduction slowing (53 ± 3 cm/s vs. 64 ± 3 cm/s; p = 0.005). CONCLUSIONS: Pressure-induced RVF is associated with electrophysiologic remodeling of the atrophic LV.


Subject(s)
Epicardial Mapping , Ventricular Dysfunction, Right/physiopathology , Ventricular Pressure/physiology , Ventricular Remodeling/physiology , Action Potentials , Animals , Atrophy , Heart Ventricles/pathology , Hypertension, Pulmonary/physiopathology , Immunohistochemistry , In Vitro Techniques , Male , NAV1.5 Voltage-Gated Sodium Channel , Patch-Clamp Techniques , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction , Sodium Channels/metabolism
3.
Europace ; 13(12): 1753-9, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21784747

ABSTRACT

AIMS: Right ventricular (RV) failure in patients with chronic thromboembolic pulmonary hypertension (CTEPH), and other types of pulmonary arterial hypertension is associated with right-to-left ventricle (LV) delay in peak myocardial shortening and, consequently, the onset of diastolic relaxation. We aimed to establish whether RV pacing may resynchronize the onsets of RV and LV diastolic relaxation, and improve haemodynamics. METHODS AND RESULTS: Fourteen CTEPH patients (mean age 63.7 ± 12.0 years, 10 women) with large (≥60 ms) RV-to-LV delay in the onset of diastolic relaxation (DIVD, diastolic interventricular delay) were studied. Temporary RV pacing was performed by atrioventricular (A-V) sequential pacing with incremental shortening of A-V delay to advance RV activation. Effects were assessed using tissue Doppler echocardiography and LV pressure-conductance catheter measurements in a subset of patients. Compared with right atrial pacing, RV pacing at optimal A-V delay (average 140 ± 22 ms, range 120-180 ms) resulted in significant DIVD reduction (59 ± 19 to 3 ± 22 ms, P < 0.001), and increase in LV stroke volume as measured by LV outflow tract velocity-time integral (14.9 ± 2.8 to 16.9 ± 3.0 cm, P < 0.001), along with enhanced global RV contractility and LV diastolic filling. CONCLUSION: Right-to-left ventricle resynchronization of the onset of diastolic relaxation results in stroke volume increase in CTEPH patients. Whether RV pacing may be a novel therapeutic target in RV failure following chronic pressure overload remains to be investigated.


Subject(s)
Cardiac Pacing, Artificial/methods , Heart Ventricles/physiopathology , Hemodynamics/physiology , Hypertension, Pulmonary/complications , Thromboembolism/complications , Ventricular Dysfunction, Right/physiopathology , Ventricular Dysfunction, Right/therapy , Adult , Aged , Aged, 80 and over , Cardiac Output/physiology , Chronic Disease , Diastole/physiology , Electrocardiography , Female , Humans , Male , Middle Aged , Stroke Volume/physiology , Ventricular Dysfunction, Right/etiology
4.
Am Heart J ; 161(6): 1046-52, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21641349

ABSTRACT

BACKGROUND: In chronic thromboembolic pulmonary hypertension, right ventricular (RV) pressure overload causes RV remodeling and dysfunction. Successful pulmonary endarterectomy (PEA) initiates restoration of RV remodeling and global function. Little is known on the restoration of systolic and diastolic RV function. Using transthoracic echocardiography, we studied the time course and extent of postoperative restoration of systolic and diastolic RV function. METHODS: In chronic thromboembolic pulmonary hypertension (n = 55, 36 women, age 52 ± 14 years), transthoracic echocardiography was performed before PEA (pre-PEA) and 2 weeks, 3 months, and 1 year postoperatively. RESULTS: Two weeks postoperatively, RV afterload and dimension had decreased significantly, without further improvement during follow-up. Global RV function, expressed by the myocardial performance index, showed a gradual improvement (from pre-PEA 0.58 ± 0.29 to 0.45 ± 0.38, 0.39 ± 0.19, and 0.37 ± 0.18). In contrast, 2 weeks after PEA systolic RV function, as assessed by tricuspid annular plane systolic velocity excursion and peak tricuspid annular systolic velocity of the RV, had worsened, with a subsequent incomplete restoration during follow-up: tricuspid annular plane systolic velocity excursion from 19.3 ± 5.0 to 12.4 ± 2.5, 15.3 ± 3.0, and 16.8 ± 2.9 mm and systolic velocity of the right ventricle from 11.4 ± 3.0 to 9.6 ± 2.0, 10.0 ± 1.8, and 10.3 ± 1.7 cm/s. Postoperative diastolic RV function also showed a biphasic response: tricuspid inflow-to-annulus ratio from 6.1 ± 3.0 to 9.5 ± 3.5, 6.8 ± 2.4, and 6.3 ± 2.2 cm/s. Dynamics and ultimate level of restoration of systolic and diastolic RV function were similar in patients with and without residual pulmonary hypertension. CONCLUSIONS: Postoperative reduction in RV afterload caused an immediate improvement in RV dimension and global function. In contrast, systolic and diastolic RV function deteriorated after PEA with subsequently a gradual yet incomplete restoration during 1-year follow-up.


Subject(s)
Endarterectomy , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/surgery , Pulmonary Artery/surgery , Ventricular Function, Right , Adult , Aged , Chronic Disease , Female , Hemodynamics , Humans , Hypertension, Pulmonary/etiology , Male , Middle Aged , Pulmonary Embolism/complications , Recovery of Function , Time Factors
5.
J Am Coll Cardiol ; 57(8): 921-8, 2011 Feb 22.
Article in English | MEDLINE | ID: mdl-21329838

ABSTRACT

OBJECTIVES: We sought to study whether patients with right ventricular failure (RVF) secondary to chronic thromboembolic pulmonary hypertension (CTEPH) have reduced left ventricular (LV) mass, and whether LV mass reduction is caused by atrophy. BACKGROUND: The LV in patients with CTEPH is underfilled (unloaded). LV unloading may cause atrophic remodeling that is associated with diastolic and systolic dysfunction. METHODS: We studied LV mass using cardiac magnetic resonance imaging (MRI) in 36 consecutive CTEPH patients (before/after pulmonary endarterectomy [PEA]) and 11 healthy volunteers selected to match age and sex of patients. We studied whether LV atrophy is present in monocrotaline (MCT)-injected rats with RVF or controls by measuring myocyte dimensions and performing in situ hybridization. RESULTS: At baseline, CTEPH patients with RVF had significantly lower LV free wall mass indexes than patients without RVF (35 ± 6 g/m(2) vs. 44 ± 7 g/m(2), p = 0.007) or volunteers (42 ± 6 g/m(2), p = 0.006). After PEA, LV free wall mass index increased (from 38 ± 6 g/m(2) to 44 ± 9 g/m(2), p = 0.001), as right ventricular (RV) ejection fraction improved (from 31 ± 8% to 56 ± 12%, p < 0.001). Compared with controls, rats with RVF had reduced LV free wall mass and smaller LV free wall myocytes. Expression of atrial natriuretic peptide was higher, whereas that of α-myosin heavy chain and sarcoplasmic reticulum calcium ATPase-2 were lower in RVF than in controls, both in RV and LV. CONCLUSIONS: RVF in patients with CTEPH is associated with reversible reduction in LV free wall mass. In a rat model of RVF, myocyte shrinkage due to atrophic remodeling contributed to reduction in LV free wall mass.


Subject(s)
Heart Failure/diagnosis , Hypertension, Pulmonary/complications , Myocardium/pathology , Stroke Volume/physiology , Ventricular Dysfunction, Right/complications , Ventricular Remodeling/physiology , Adult , Aged , Animals , Atrophy/pathology , Case-Control Studies , Disease Models, Animal , Endarterectomy/methods , Female , Heart Failure/etiology , Humans , Hypertension, Pulmonary/diagnosis , Magnetic Resonance Imaging/methods , Male , Middle Aged , Prognosis , Pulmonary Embolism/complications , Pulmonary Embolism/diagnosis , Pulmonary Embolism/surgery , Rats , Reference Values , Retrospective Studies , Ventricular Dysfunction, Right/diagnosis
6.
Eur J Nucl Med Mol Imaging ; 37(11): 2079-85, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20603720

ABSTRACT

PURPOSE: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a myocardial disease that predominantly affects the right ventricle (RV). Its hallmark feature is fibro-fatty replacement of RV myocardium. However, patchy inflammatory infiltrates in the RV are also consistently reported using autopsy and myocardial biopsy. Although the role of inflammation in ARVC/D is unresolved, the ability to assess inflammation non-invasively may aid in the diagnostic process. We aimed to establish whether cardiac inflammation can be assessed non-invasively in ARVC/D patients. METHODS: In eight ARVC/D patients and nine controls (haematology/oncology patients), the level of inflammatory activation was assessed by measuring plasma levels of inflammatory cytokines. Regional myocardial inflammation was assessed with (67)Ga scintigraphy. RESULTS: ARVC/D patients had higher plasma levels than controls of the pro-inflammatory cytokines interleukin (IL)-1ß (1.22 ± 0.07 vs 0.08 ± 0.01 pg/ml, p < 0.0001), IL-6 (3.16 ± 0.44 vs 0.38 ± 0.04 pg/ml, p < 0.0001) and tumour necrosis factor (TNF)-α (9.16 ± 0.90 vs 0.40 ± 0.06 pg/ml, p < 0.0001), while levels of the anti-inflammatory cytokine IL-10 were not significantly different (1.36 ± 0.15 vs 1.20 ± 0.30 pg/ml, p = 0.74). (67)Ga uptake in the RV was higher in ARVC/D patients than in controls. In ARVC/D patients, (67)Ga uptake in the RV wall was higher than in the interventricular septum or left ventricular wall. CONCLUSION: Inflammation in the RV wall of ARVC/D patients can be detected non-invasively with the combined analysis of plasma levels of inflammatory cytokines and cardiac (67)Ga scintigraphy.


Subject(s)
Arrhythmogenic Right Ventricular Dysplasia/complications , Inflammation/complications , Inflammation/diagnosis , Adult , Biological Transport , Cytokines/blood , Female , Gallium Radioisotopes/metabolism , Humans , Inflammation/blood , Inflammation/diagnostic imaging , Male , Middle Aged , Myocardium/metabolism , Radionuclide Imaging , Young Adult
7.
Echocardiography ; 27(10): 1247-55, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20584069

ABSTRACT

BACKGROUND: Ventricular systolic and diastolic function, as measured by echocardiography, are diminished in patients with a systemic right ventricle (RV). As the clinical implications of these finding remained unknown, we aimed to identify echocardiographic parameters of systolic and diastolic ventricular function that are independent determinants of the clinical condition in these patients. METHODS: Forty-six adult patients (61% male; mean age 33 [range 18-69] years) with a systemic RV underwent echocardiography to assess qualitative and quantitative systolic and diastolic function of the systemic RV and the subpulmonary left ventricle (LV). Uni- and multivariate linear regression analyses were performed to identify independent echocardiographic determinants for NYHA class, maximal exercise capacity (V'O(2peak)) and NT-proBNP levels. RESULTS: We found qualitative assessment of RV and LV function to be significantly associated with NYHA class (RV: ß= 0.26; P = 0.05 and LV: ß= 0.82; P < 0.01), V'O(2peak) (RV: ß=-10.4; P < 0.05 and LV: ß=-18.4; P < 0.05) and NT-proBNP levels (RV: ß= 0.58; P < 0.01 and LV: ß= 1.40; P < 0.001). Tricuspid annulus plane systolic excursion (TAPSE) was significantly associated with NYHA class (ß=-0.92; P = 0.001), V'O(2peak) (ß= 18.5; P = 0.05), and serum NT-proBNP levels (ß=-1.00; P < 0.05). Associations between quantitative parameters of systolic subpulmonary LV function and clinical parameters were less distinct. We found no associations between RV and LV diastolic function and clinical parameters. CONCLUSIONS: Qualitative function of the systemic RV and the subpulmonary LV, and TAPSE, are determinants of clinical condition in patients with a systemic RV. These patients' clinical condition could not be determined by echocardiographically measured diastolic RV function, and systolic and diastolic LV function.


Subject(s)
Echocardiography/methods , Heart Ventricles/abnormalities , Heart Ventricles/diagnostic imaging , Ventricular Dysfunction, Left/complications , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Right/complications , Ventricular Dysfunction, Right/diagnostic imaging , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young Adult
8.
Eur J Heart Fail ; 12(7): 653-8, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20495202

ABSTRACT

AIMS: Inflammatory activation plays an important role in the pathogenesis and progression of left ventricular (LV) heart failure. In right ventricular (RV) heart failure, little is known about the role of inflammatory activation. We aimed to study the role of inflammatory activation in RV heart failure by serial monitoring during disease progression. METHODS AND RESULTS: Right ventricular heart failure was induced in male Wistar rats by intraperitoneal injection of monocrotaline (MCT). Two groups were studied: MCT-treated rats (MCT-rats), and age-matched controls (CON-rats). Serial echocardiography and in vivo 67-Gallium ((67)Ga) scintigraphy were performed. Local inflammation in the RV was assessed by (i) ex vivo semi-quantitative (67)Ga autoradiography, (ii) immunohistochemistry of myeloperoxidase (MPO), a marker of neutrophil activity, and (iii) mRNA assays of tumour necrosis factor-alpha (TNF-alpha). In MCT-rats, (67)Ga scintigraphy showed increased myocardial uptake which started during the early stages of RV disease. (67)Ga autoradiography revealed that this increased (67)Ga uptake occurred in the RV and inter-ventricular septum, but not in the LV. The stage-dependent increases of in vivo (67)Ga RV myocardial uptake were paralleled by increases in mRNA gene expression for TNF-alpha in RV, and increased MPO staining in RV. CONCLUSION: Development and progression of RV heart failure is associated with an early increase in RV inflammation. (67)Ga scintigraphy may be used for the serial assessment of inflammation and monitoring of disease progression in RV heart failure.


Subject(s)
Heart Failure/physiopathology , Inflammation/etiology , Animals , Autoradiography , Disease Models, Animal , Disease Progression , Gallium Radioisotopes , Gene Expression Profiling , Heart Failure/blood , Heart Failure/chemically induced , Hypertrophy, Right Ventricular/blood , Immunochemistry , Male , Monocrotaline/adverse effects , Myocardium/metabolism , Neutrophil Activation/physiology , Peroxidase/metabolism , Radionuclide Imaging , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/analysis , Ventricular Dysfunction, Right/blood , Ventricular Dysfunction, Right/complications , Ventricular Dysfunction, Right/diagnostic imaging
9.
Circ Arrhythm Electrophysiol ; 2(5): 555-61, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19843924

ABSTRACT

BACKGROUND: Delayed left ventricle (LV)-to-right ventricle (RV) peak shortening results in cardiac output reduction in patients with chronic thromboembolic hypertension (CTEPH) and other types of pulmonary arterial hypertension. Why the synchrony between LV and RV is lost is unknown. We hypothesized that RV electrophysiological remodeling, notably, conduction slowing and action potential prolongation, contribute to this loss in synchrony. METHODS AND RESULTS: We conducted epicardial mapping during pulmonary endarterectomy in 26 patients with CTEPH and compared these findings with clinical, hemodynamic, and echocardiographic variables. We consecutively placed a multielectrode grid on the epicardium of the RV free wall and LV lateral wall. These regions corresponded to RV and LV areas where echocardiographic Doppler sample volumes were placed to measure RV-to-LV diastolic interventricular delay. RV and LV epicardial action potential duration was assessed by measuring activation-recovery interval. Onset of diastolic relaxation of RV free wall with respect to LV lateral wall (diastolic interventricular delay) was delayed by 38+/-31 ms in patients with CTEPH versus -12+/-13 ms in control subjects (P<0.001), because, in patients with CTEPH, RV completed electric activation later than LV (65+/-20 versus 44+/-7 ms, P<0.001) and epicardial action potential duration, as assessed by activation-recovery interval measurement, was longer in RV free wall than in LV lateral wall (253+/-29 versus 240+/-22 ms, P<0.001). CONCLUSIONS: Additive effects of electrophysiological changes in RV, notably, conduction slowing and action potential prolongation, assessed by epicardial activation-recovery interval, contribute to diastolic interventricular delay in patients with CTEPH.


Subject(s)
Heart Conduction System/physiopathology , Hypertension, Pulmonary/physiopathology , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Right/physiopathology , Action Potentials/physiology , Analysis of Variance , Body Surface Potential Mapping/methods , Diastole/physiology , Echocardiography, Doppler , Endarterectomy , Female , Heart Conduction System/diagnostic imaging , Humans , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/surgery , Linear Models , Male , Middle Aged , Prospective Studies , Statistics, Nonparametric , Stroke Volume , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Right/diagnostic imaging
10.
J Nucl Med ; 50(8): 1371-7, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19617336

ABSTRACT

UNLABELLED: Right ventricular (RV) function is the major determinant of survival in patients with pulmonary hypertension. Yet, the pathophysiologic basis of RV disease is unresolved. We aimed to study the role of apoptosis in RV disease by monitoring it serially during disease progression using in vivo (99m)Tc-annexin-V ((99m)Tc-annexin) scintigraphy and study whether the reduction in apoptosis resulting from chronic treatment with valsartan can be detected by (99m)Tc-annexin scintigraphy. METHODS: RV disease after pulmonary hypertension was induced by monocrotaline injection in rats. The following 3 groups were studied: rats treated with monocrotaline (monocrotaline rats), rats treated with monocrotaline plus valsartan (valsartan rats), and age-matched controls (control rats). Serial echocardiography and in vivo (99m)Tc-annexin scintigraphy were performed. Apoptosis was confirmed by (99m)Tc-annexin autoradiography and terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling. Fibrosis was assessed by picrosirius red staining. RESULTS: In monocrotaline rats, in vivo (99m)Tc-annexin uptake peaked early and declined thereafter but remained elevated, compared with baseline. These stage-dependent changes of in vivo (99m)Tc-annexin uptake were paralleled by changes in autoradiography and terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling. Valsartan rats had longer RV failure-free survival than did monocrotaline rats and had reduced apoptosis. These changes were accompanied by commensurate delays in RV hypertrophy and RV dilation. Valsartan rats also had less fibrosis than monocrotaline rats at all disease stages. CONCLUSION: RV disease progression is associated with an early increase in RV apoptosis, as monitored using serial in vivo (99m)Tc-annexin scintigraphy. Delay in RV disease progression by valsartan is accompanied by reduction in RV apoptosis. Apoptosis plays a role in RV disease progression and may be assessed by serial in vivo (99m)Tc-annexin scintigraphy.


Subject(s)
Annexin A5 , Organotechnetium Compounds , Ventricular Dysfunction, Right/diagnostic imaging , Animals , Apoptosis , Disease Progression , Male , Radionuclide Imaging , Radiopharmaceuticals , Rats , Rats, Wistar , Reproducibility of Results , Sensitivity and Specificity , Ventricular Dysfunction, Right/pathology
11.
Eur J Echocardiogr ; 10(3): 433-8, 2009 May.
Article in English | MEDLINE | ID: mdl-19042941

ABSTRACT

AIMS: In patients with pulmonary hypertension (PH), elevated endothelin-1 levels are associated with prolonged duration of right ventricular (RV) contraction, which induces leftward ventricular septal bowing with impaired left diastolic filling. We hypothesized that baseline RV contraction duration predicts efficacy of endothelin receptor antagonist, bosentan. METHODS AND RESULTS: Eighteen PH patients (age 57, range 35-79 years, 33% male) received bosentan. Six minute walk distance (6-MWD) and echocardiography were performed at baseline and after 1 year follow-up. After 1 year of treatment, 6-MWD increased (mean 60 +/- 41 m) in 67% of patients (responders). Baseline RV contraction duration was longer in responders, compared with non-responders (612 +/- 66 vs. 514 +/- 23 ms; P < 0.01). A baseline RV contraction duration >550 ms was associated with improved 6-MWD (sensitivity 83%, specificity 83%; P < 0.01). CONCLUSION: An improvement of 6-MWD during bosentan treatment was associated with a decrease in RV contraction duration and could be predicted by a baseline RV contraction duration >550 ms.


Subject(s)
Antihypertensive Agents/therapeutic use , Heart Ventricles/diagnostic imaging , Hypertension, Pulmonary , Myocardial Contraction , Sulfonamides/therapeutic use , Ventricular Function, Right/drug effects , Adult , Aged , Bosentan , Female , Hemodynamics/drug effects , Humans , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/drug therapy , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Ultrasonography , Walking
12.
Europace ; 10(1): 99-104, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18094018

ABSTRACT

AIMS: Some atrial fibrillation (AF) patients develop excessive QTc prolongation and torsade de pointes when they take QTc-prolonging antiarrhythmic drugs (class IA/III) immediately after termination of AF. We hypothesized that this is caused by changes in ventricular repolarization during AF. We aimed to establish whether such 'ventricular repolarization remodelling' occurs. METHODS AND RESULTS: We studied all patients who visited our cardiac emergency room with AF and converted to sinus rhythm (SR) in a 30 months' period. We defined four groups: (i) no antiarrhythmic drugs, electrical cardioversion (n = 30), (ii) no antiarrhythmic drugs, spontaneous AF termination (n = 19), (iii) antiarrhythmic drugs, electrical cardioversion (n = 29), and (iv) antiarrhythmic drugs, spontaneous AF termination (n = 9). We studied QTc duration at SR before AF (SR(baseline)), immediately after termination of AF (SR(postAF)), and at follow-up (SR(followup): > or =7 days after SR(postAF)). Moreover, we studied determinants of QTc prolongation at SR(postAF). We found that, in all groups, QTc at SR(postAF) was significantly and transiently prolonged compared with SR(baseline). Although of limited magnitude on average (approximately 5%), the increase was substantial (approximately 15%) in some individuals. The only independent predictor of the magnitude of QTc prolongation was QTc duration at SR(baseline); this relation had a negative correlation. CONCLUSION: AF causes ventricular repolarization remodelling, resulting in QTc prolongation. QTc prolongation is substantial in some patients and may render these patients vulnerable to pro-arrhythmia from class IA/III antiarrhythmic drugs immediately after termination of AF.


Subject(s)
Atrial Fibrillation/physiopathology , Electrocardiography , Ventricular Remodeling/physiology , Aged , Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Atrial Fibrillation/therapy , Combined Modality Therapy , Electric Countershock/methods , Female , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Humans , Linear Models , Male , Middle Aged , Retrospective Studies
13.
Eur Heart J ; 28(7): 842-9, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17341501

ABSTRACT

AIMS: To study whether pre-operative assessment, using echocardiography, of the timing of a particular feature in the pulmonary flow (pulmonary flow systolic notch) may predict in-hospital mortality and mid-term haemodynamic improvement after pulmonary endarterectomy (PEA) for chronic thrombo-embolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: Fifty-eight of 61 consecutive CTEPH patients (aged 53 +/- 14 years; 36 women) who underwent PEA between June 2002 and June 2005 were studied. Clinical, haemodynamic, and echocardiographic variables were assessed pre-operatively and at 3 months post-PEA. Timing of the notch was expressed as notch ratio (NR). Pre-operatively, seven patients had no notch, 33 had NR < 1.0, and 18 had NR > 1.0. NR was associated with in-hospital mortality (P < 0.01). Moreover, multivariable analysis revealed that among pre-operative variables, NR was an independent predictor of residual-increased pulmonary artery systolic pressure (>40 mmHg) at 3 months post-PEA (P = 0.01). Receiver operator characteristic analysis established NR = 1.0 as optimal cutoff to distinguish patients at risk of such unfavourable outcomes, with NR > 1.0 conferring higher risk. CONCLUSION: NR is related with in-hospital mortality and residual pulmonary hypertension after PEA. NR > 1.0 is associated with a higher risk of such unfavourable outcomes. NR may be considered a determinant of eligibility for PEA.


Subject(s)
Hypertension, Pulmonary/diagnostic imaging , Thromboembolism/diagnostic imaging , Analysis of Variance , Blood Pressure/physiology , Chronic Disease , Endarterectomy , Female , Hospital Mortality , Humans , Hypertension, Pulmonary/mortality , Hypertension, Pulmonary/surgery , Male , Middle Aged , Observer Variation , Preoperative Care/methods , Pulmonary Circulation/physiology , Thromboembolism/mortality , Thromboembolism/surgery , Treatment Outcome , Ultrasonography
14.
J Am Soc Echocardiogr ; 19(10): 1272-9, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17000367

ABSTRACT

BACKGROUND: The temporal relations between the onset of echocardiographic changes and clinical diagnosis of right ventricular (RV) failure are unresolved. We have characterized such relations in a rat monocrotaline (MCT) model of RV failure. METHODS: Eight-week-old male Wistar rats were injected with MCT (60 mg/kg) or vehicle and underwent serial echocardiography. RV free-wall thickness (RVWT), pulmonary artery acceleration time normalized to cycle length (PAAT/CL), RV end-diastolic diameter (RVEDD), and tricuspid annular plane systolic excursion (TAPSE) were measured. RESULTS: Significant differences in echocardiographic parameters between MCT-treated and control rats were found as early as 14 days before RV failure for RVWT, 10 days for PAAT/CL, and 7 days for RVEDD and TAPSE. The time intervals between the onset of changes in RVWT, PAAT/CL, RVEDD, and TAPSE and diagnosis of RV failure were 11.3 +/- 0.8, 10.9 +/- 0.7, 6.5 +/- 0.5, and 5.4 +/- 0.7 days, respectively. The sequence of echocardiographic changes was consistent in all animals during development of RV failure. CONCLUSIONS: Pulmonary hypertension (assessed by PAAT/CL) and RV free-wall thickening (characterized by RVWT) precede RV dilation and RV systolic dysfunction (measured by RVEDD and TAPSE, respectively). Echocardiographic analysis permits accurate determination of the stage of disease development in MCT-induced RV failure.


Subject(s)
Disease Models, Animal , Heart Failure/diagnostic imaging , Heart Failure/etiology , Ventricular Dysfunction, Right/complications , Ventricular Dysfunction, Right/diagnostic imaging , Animals , Disease Progression , Heart Failure/chemically induced , Heart Failure/classification , Male , Monocrotaline , Rats , Rats, Wistar , Reproducibility of Results , Sensitivity and Specificity , Ultrasonography , Ventricular Dysfunction, Right/chemically induced , Ventricular Dysfunction, Right/classification
15.
Naunyn Schmiedebergs Arch Pharmacol ; 373(6): 391-400, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16932922

ABSTRACT

Various animal models of pulmonary hypertension (PH) exist, among which injection of monocrotaline (MCT) and exposure to hypoxia are used most frequently. These animal models have not only been used to characterize the pathophysiology of PH and its sequelae such as right ventricular hypertrophy and failure, but also to test novel therapeutic strategies. This manuscript summarizes the available treatment studies in animal models of PH, and compares the findings to those obtained in patients with PH. The analysis shows that all approaches which have proven successful in patients, most notably prostacyclin and its analogs and endothelin receptor antagonists, are also effective in various animal models. However, the opposite it not always true. Therefore, promising results in animals have to be interpreted carefully until confirmed in clinical studies.


Subject(s)
Hypertension, Pulmonary/drug therapy , Animals , Animals, Genetically Modified , Disease Models, Animal , Ductus Arteriosus/physiology , Embolism/complications , Embolism/physiopathology , Humans , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/physiopathology , Hypoxia/physiopathology , Monocrotaline , Poisons
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