Refined balloon pulmonary angioplasty-A therapeutic option in very elderly patients with chronic thromboembolic pulmonary hypertension.

INTRODUCTION/OBJECTIVES: Balloon pulmonary angioplasty (BPA) is a developing treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, to our knowledge there are no published data on BPA in CTEPH subjects aged 75 or over. The aim of the study was to analyze clinical and hemodynamic outcomes of sequential BPA in very elderly patients disqualified from pulmonary endarterectomy (PEA). PATIENTS AND METHODS: We enrolled 10 patients (4 male, 6 female, median age 81 [75-88]) with confirmed CTEPH, mPAP > 30 mmHg, and WHO class > II, disqualified from PEA. Overall, 10 patients underwent 39 BPA sessions (mean 3.9 sessions per patient, range 1-9), and 70 pulmonary arteries were dilated, (mean 6.5 vessels per patient, range 1-14). RESULTS: Pulmonary angioplasty resulted in significant clinical and hemodynamic improvement in every patient: 6 MWT distance increased from a median of 221 m (80-320) to 345 (230-455) and plasma NT-proBNP levels decreased (P < 0.01). Sequential BPA resulted in normalization of mPAP (<25 mmHg) in 6 of 10 patients and mPAP decreased to 25-30 mmHg in three others. In the whole group mPAP decreased from 41 (31-53) mmHg to 23 (17-33) mmHg (P < 0.01). Overall, mean PAP and PVR decreased significantly in all cases, while CO and CI increased (P < 0.01). No severe complications occurred during BPA and over a median follow-up of 553 days (range 81-784), and all patients are still alive and in good general health. CONCLUSION: This study demonstrated the safety and efficacy of refined BPA in CTEPH patients aged 75 or over, disqualified from PEA. Refined BPA may emerge as an alternative therapeutic strategy in very elderly CTEPH patients who are suitable for surgery, but this requires further validation in a large prospective study.

Cardiac autonomic function in type 1 and type 2 myotonic dystrophy.

OBJECTIVE: The aim of this study was to evaluate cardiac autonomic nervous system function using Holter-derived and standard electrocardiographic parameters in patients with myotonic dystrophy (dystrophia myotonica, DM) and no clinically overt heart involvement. METHODS: Eighty-four DM patients without conditions potentially influencing cardiac autonomic function were enrolled in the study: 44 with DM type 1 and 40 with DM type 2 (mean age 34.9 ± 11.5 and 47.8 ± 13.5 years, respectively). Two corresponding control groups of aged-matched healthy subjects were selected for DM1 (n = 35) and for DM2 (n = 30). Standard electrocardiography for QT interval dispersion and 24-h Holter monitoring with time-domain heart rate variability and heart rate turbulence were performed. RESULTS: No significant differences in time-domain heart rate variability parameters between DM1 or DM2 subjects and controls were observed. However, heart rate turbulence parameters were significantly impaired in DM1 patients as compared to their controls: turbulence onset (p = 0.025), and turbulence slope (p = 0.018). Moreover, turbulence slope was also impaired in DM2 patients (p = 0.042). As compared to controls, we observed an increased QT dispersion, both in DM1 (p = 0.003) and also in DM2 patients (p < 0.0001). No relationship between disease duration or neurological status and time-domain heart rate variability, heart rate turbulence, and QT dispersion was observed. INTERPRETATION: Despite normal time-domain heart rate parameters, impaired heart rate turbulence and increased QT dispersion may suggest cardiac autonomic nervous system dysfunction in DM patients. The present study is the first one in which heart rate turbulence and QT dispersion assessment were examined both in DM1 and DM2 patients.

Supraventricular and Ventricular Arrhythmias Are Related to the Type of Myotonic Dystrophy but Not to Disease Duration or Neurological Status.

BACKGROUND: Patients with myotonic muscular dystrophy (dystrophia myotonica, DM) are at risk of sudden cardiac death due to diverse arrhythmias, especially progressive atrioventricular (AV) conduction abnormalities. However, there are limited data on supraventricular and potentially life-threatening ventricular arrhythmias, especially according to type 1 and type 2 DM. METHODS: A group of 94 unselected consecutive patients with genetically confirmed DM and 45 healthy controls underwent electrocardiography, echocardiography, and 24-hour Holter monitoring. DM1 was diagnosed in 51, while DM2 in 43 patients (with mean age of 37.3 ± 12.5 and 48.3 ± 13.3 years, respectively). RESULTS: DM1 subjects presented more frequently intraventricular conduction defects (29.4% vs 6.6%, P = 0.0003) and first-degree AV block (25.0% vs 4.6%, P = 0.008) than DM2 patients. Nonsustained supraventricular tachycardia (37.2% vs 3.8%, P = 0.001) and nonsustained ventricular tachycardia and/or R-on-T ventricular beats (23.2% vs 7.8%, P = 0.04) were more frequently observed in DM2 than in DM1. No relationship between disease duration and neurological status and occurrence of arrhythmias was observed. Multivariate analysis showed that independent predictor for bradyarrhythmias occurrence was DM1 only (odds ratio [OR] 6.4, 95% confidence interval [CI] 2.0-20.8, P = 0.002), while for supraventricular or ventricular arrhythmias occurrence it was DM2 (OR 4.1, 95% CI 1.5-11.4, P = 0.007) and increased age (OR 1.09, 95% CI 1.05-1.15, P < 0.0001). CONCLUSIONS: In the relatively large groups of DM1 and DM2 patients, we observed frequent various arrhythmias, which warrant their close cardiac monitoring. DM1 subjects when compared to DM2 presented more frequently intraventricular and AV conduction defects. However, all types of tachyarrhythmias (except atrial fibrillation) were more frequently observed in DM2 patients.

Six-minute walk test reflects neurohormonal activation and right ventricular function in systemic sclerosis patients.

OBJECTIVES: Heart and pulmonary involvement is a leading cause of systemic sclerosis (SSc)-related deaths. The six-minute walk test (6MWT) is a simple and reproducible test commonly used to evaluate exercise capacity. We tried to assess a potential relationship between exercise capacity assessed by 6MWT, echocardiographic parameters of right ventricular function and serum levels of endothelin-1 and NTproBNP. METHODS: We prospectively studied 111 consecutive patients (101F, 10M, age 54.2±13.8 years) with diagnosed SSc (mean disease duration 9±12.4 years) and a group of 21 age-matched subjects (18F, 3M, age 49.3±10.5 years). In addition to routine evaluation, 6MWT and transthoracic echocardiography (Phillips iE 33) were performed. We also measured serum endothelin-1 (Human Endothelin-1 immunoassay R & D Systems) and NT-proBNP levels (Elecsys pro-BNP immunoassay; Roche Diagnostics). RESULTS: The mean 6MWT distance was significantly shorter in the SSc group than in the controls (562.8±60.3 vs. 514.7±102.5 m, p=0.03). In the SSc group 6MWT distance correlated with ET-1 (r=-0.5, p<0.0001), NTproBNP (r=-0.4, p=0.0008) levels, and echocardiographic indices AcT (r=0.4, p=0.0002) and TRPG (r=-0.4, p=0.0011). Moreover, in patients with 6MWT distance <450 m NTproBNP and endotothelin-1 levels were significantly higher than in patients with distance >450 m (311.2, 31.1-17237 vs. 105.3, 5-17670 pg/ml, p=0.0138 and 2.9±2.2 vs. 1.4±0.7 pg/ml, p=0.0032). CONCLUSIONS: Decreased exercise capacity significantly correlates with biochemical and echocardiographic parameters of right ventricular dysfunction and neurohormonal activation providing a potential link for neuroendocrine derangement in patients with SSc.

High prevalence of severe coronary artery disease in elderly patients with non-operable chronic thromboembolic pulmonary hypertension referred for balloon pulmonary angioplasty.

INTRODUCTION: Balloon pulmonary angioplasty (BPA) is a new emerging catheter-based alternative treatment option for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). AIM: To show that all elderly CTEPH patients referred for BPA are at higher risk of obstructive coronary artery disease and that, in daily practice, they should undergo invasive coronary angiography. MATERIAL AND METHODS: Eleven patients at the age of at least 65 years (6 males, 5 females, 77.2 ±5.9 years) with confirmed non-operable type II or type III CTEPH, considered for BPA, underwent elective coronary angiography. Severe obstructive coronary artery disease (CAD) was diagnosed when stenosis of left main coronary artery ≥ 50% or stenosis of ≥ 70% of epicardial arteries was angiographically confirmed. We also screened for CAD consecutive age- and sex-matched 114 PE survivors (52 males, 62 females, 74.8 ±7.2 years) with excluded CTEPH. RESULTS: Severe CAD was more frequent in elderly patients with non-operable type II or type III CTEPH candidates for BPA than in elderly acute PE survivors with excluded CTEPH (54.5% vs. 16.7%, p < 0.01), and therefore elderly CTEPH patients referred for BPA were at higher risk of CAD (OR = 5.9, 95% CI: 1.64-21.46, p = 0.007) when compared to elderly survivors after acute PE with excluded CTEPH. CONCLUSIONS: All elderly CTEPH patients referred for BPA are at higher risk of severe CAD and should routinely undergo invasive coronary angiography before BPA.

Refined balloon pulmonary angioplasty driven by combined assessment of intra-arterial anatomy and physiology--Multimodal approach to treated lesions in patients with non-operable distal chronic thromboembolic pulmonary hypertension--Technique, safety and efficacy of 50 consecutive angioplasties.

BACKGROUND/OBJECTIVES: Balloon pulmonary angioplasty (BPA) is an emerging therapeutic method in CTEPH. We aimed to prove the safety and efficacy of refined BPA driven by combined assessment of intra-arterial anatomy (IVUS/OCT) and physiology (pulmonary pressure ratio, PPR) in non-operable distal CTEPH. METHODS: 11 pts (mean age 76, 59­84, 7 males) were enrolled in the BPA program according to the following inclusion criteria: 1. Non-operable CTEPH; 2. RHC with mPAP > 30 mm Hg; 3. At least one segmental perfusion defect at lung scintigraphy; 4. WHO class > II. Overall, 9 pts underwent 27 BPA sessions (mean 3 sessions per patient, range 1­5), 50 pulmonary arteries were dilated (mean 6 vessels per patient, range 3­9; 2.03 dilated arteries per session). All the angioplasties were performed according to an algorithm, which incorporated anatomical and functional assessment of targeted lesions. RESULTS: We performed BPA of 32 web lesions, 5 ring-like stenosis and 13 complete obstructions. BPA resulted in clinical and hemodynamic improvement. WHO class improved from pre-BPA to post-BPA (p = 0.018), and 6 MWD increased from 304 m to 384 m (p = 0.03), NT-proBNP dropped from 1248 pg/ml to 730 pg/ml (p < 0.001). Mean PAP and PVR decreased (p = 0.01), while CO and CI increased (p = 0.01). All dilated arteries were patent at angiographic reassessment. No significant complications occurred and all treated patients are still alive. Insignificant transient reperfusion pulmonary oedema occurred in only 2 patients, who responded well to supplemental oxygen. CONCLUSIONS: Refined BPA with assessment of intrapulmonary physiology using a pressure wire and precise evaluation of anatomy with IVUS and OCT provides hemodynamic and functional improvement, with minimal complications in distal non-operable CTEPH. This observation requires further validation in a large prospective study.

Serum endothelin-1 and NT-proBNP, but not ADMA, endoglin and TIMP-1 levels, reflect impaired right ventricular function in patients with systemic sclerosis.

BACKGROUND: Heart and pulmonary involvement is a leading cause of systemic sclerosis (SSc)-related deaths. OBJECTIVES: The aim of our study was to assess if biochemical markers of right ventricular (RV) overload, endothelial function and collagen metabolism can predict RV dysfunction assessed by Doppler echocardiography in SSc patients. METHODS: We prospectively studied 111 consecutive patients (101 F, 10 M, age 54.2 ± 13.8 years) with diagnosed SSc (mean disease duration 9.4 ± 11.4 years) and a group of 21 age-matched subjects (18 F, 3 M, age 49.3 + 10.5 years). We performed transthoracic echocardiography (Phillips iE 33) and measured serum endothelin-1 (ET-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), asymmetric dimethylarginine (ADMA), endoglin and human tissue inhibitor of matrix metalloproteinase (TIMP-1) concentration. RESULTS: Median serum NT-proBNP level in SSc patients was 133.5 (range 21.86-17,670 pg/ml) and was significantly higher than in controls (p = 0.0002). Moreover, the median serum ET-1 level of 1.49 (range 0.26-8.75 pg/ml) was higher in SSc patients (p = 0.002). However, no significant differences in ADMA, TIMP-1 and endoglin serum concentration between SSc patients and controls were observed. Serum NT-proBNP concentration correlated positively with echocardiographic signs of RV overload: tricuspid regurgitation pressure gradient (r = 0.38, p = 0.0004) and RV Tei index (r = 0.25, p = 0.01). ET-1 serum level correlated negatively with tricuspid annular plane systolic excursion (r = -0.4, p = 0.01) and positively with inferior vena cava diameter measured at expiration (r = 0.38, p = 0.0002). The echocardiographic signs of RV overload were significantly more pronounced in the highest NT-proBNP tertile (>195 pg/ml) group than in the lowest one (<88 pg/ml). CONCLUSIONS: Serum ET-1 and NT-proBNP, but not endoglin, ADMA and TIMP-1 levels correlating with the echocardiographic parameters of RV overload, can be considered as noninvasive indicators of RV dysfunction in SSc patients.

Heart diastolic dysfunction in patients with systemic sclerosis.

INTRODUCTION: There are limited data on left (LV) and right ventricular (RV) diastolic function in systemic sclerosis (SSc) patients especially in relation to biomarkers of matrix remodeling. The aim of the study was to analyze LV and RV myocardial diastolic function in SSc patients at baseline and after at least 1 year of follow-up and its relation to serum tissue inhibitors of metalloproteinase 1 (TIMP-1) level. MATERIAL AND METHODS: We prospectively studied 111 SSc patients (101 female, 10 male, age 54.2 ±13.8 years) and 21 age-matched controls (18 female, 3 male, age 49.3 ±10.5 years). After at least 1 year of observation (3.0 ±1.1 years) we reevaluated 69 of the SSc patients. Transthoracic echocardiography (Philips, iE33) for assessment of LV and RV diastolic function was performed and TIMP-1 serum level was measured. RESULTS: Impaired LV relaxation was observed in 38 (34%) SSc patients and in 1 (5%) of the controls (p < 0.001). The mean E/A ratio was lower in patients with SSc than in controls (p = 0.002) and significantly decreased after the follow-up period (p = 0.02). Impaired RV relaxation was detected in 25 (22.5%) SSc patients and in 1 (5%) control subject (p < 0.001) but did not deteriorate after follow-up. Mean serum level of TIMP-1 was significantly elevated in the follow-up group compared to baseline examination (p = 0.0001). Serum TIMP-1 level correlated positively with E/E', both septal and lateral (r = 0.4, p = 0.002 and r = 0.32, p = 0.01). CONCLUSIONS: The LV and RV relaxation is impaired in SSc patients. Moreover, left ventricular diastolic function deteriorated after the follow-up period. The TIMP-1 serum levels correlate with echocardiographic parameters, providing a potent link for LV diastolic function and matrix remodeling in patients with SSc.

Exaggerated increase of exercise-induced pulmonary artery pressure in systemic sclerosis patients predominantly results from left ventricular diastolic dysfunction.

OBJECTIVE: High prevalence of exaggerated pulmonary artery pressure response to exercise (EPAPR) was reported in patients with systemic sclerosis (SSc). However, pathophysiology of this phenomenon has not been well defined. Therefore, we evaluated the frequency and potential aetiology of EPAPR in SSc patients. METHODS: We included 85 patients (79 female, 6 male, mean age 54.3 ± 13.9 years) with SSc. Transthoracic echocardiography followed by exercise Doppler echocardiography (EDE) were performed. A positive EDE was defined when at least 20 mmHg increase of tricuspid regurgitation peak gradient (TRPG) was recorded. Right heart catheterization (RHC) with exercise was performed in positive EDE patients and in subjects with resting TRPG >31 mmHg. RESULTS: Resting TRPG >31 mmHg and/or positive EDE was found in 30 patients and they were referred to RHC. Finally, RHC was performed in 20 patients (16 pts resting TRPG >31 mmHg and 4 others normal resting TRPG and positive EDE). In 12 (60 %) of them an EPAPR with elevated pulmonary capillary wedge pressure (PCWP) was observed. Interestingly, mean left atrium (LA) diameter was greater in an EPAPR with elevated PCWP patients than in subjects with normal exercise response (39.36 ± 5.6 vs. 35.53 ± 3.48, p = 0.03). In EPAPR with elevated PCWP group greater mean value of E/E' of mitral lateral annulus was observed (7.98 ± 3.35 vs. 6.27 ± 1.94, p = 0.03). In the univariate logistic regression analysis increased LA diameter was significant predictor of EPAPR with elevated PCWP (OR 1.199, 95 % CI 1.029-1.396, p = 0.019). CONCLUSIONS: Despite very well-known risk of PAH in systemic sclerosis patients, the excessive increase of PAP during exercise is more commonly caused by left ventricular diastolic dysfunction than pulmonary arterial vasculopathy.

Usefulness of echocardiography in the identification of an excessive increase in pulmonary arterial pressure in patients with systemic sclerosis.

BACKGROUND: In systemic sclerosis (SSc), changes in the lungs and pulmonary hypertension (PH) are complications most adversely affecting the prognosis. Given the availability of specific treatment, early diagnosis of PH is very important. Exercise echocardiography, by increasing the patient's cardiac output, makes it possible to identify patients with elevated pulmonary artery pressure (PAP) during exercise. The diagnostic role of exercise echocardiography is still unclear, mainly because of the lack of prospective studies. AIM: To identify SSc patients with abnormally elevated PAP at rest or with a significant increase PAP during exercise, subsequently verified by right heart catheterisation (RHC). METHODS: A total of 71 consecutive patients (67 females and 4 males, mean age 56.9 ± 17.1 years) with SSc diagnosed according to the American College of Rheumatology criteria were enrolled in this prospective study. The patients underwent transthoracic echocardiography (Philips iE33) with the measurement of tricuspid regurgitation peak gradient (TRPG) and an exercise test involving the standard treadmill exercise according to the Bruce protocol with the evaluation of TRPG at 1 min following the completion of exercise. The PH was suspected when TRPG at rest was 〉 31 mm Hg (V(max) 〉 2.8 m/s) or increased by at least 20 mm Hg from baseline following exercise. Patients with suspected PH were referred for resting and exercise RHC. RESULTS: The exercise testing was performed in 67 patients revealing normal left ventricular (LV) systolic function in all of them. The mean LV ejection fraction was 66.1% ± 3.9%. The TRPG at rest could be recorded in 65 (97%) patients with the mean value of 26.9 ± ± 7.6 mm Hg (range 17-57 mm Hg). A resting TRPG of 〉 31 mm Hg, suggestive of possible PH, was demonstrated in 14 (21%) patients. During exercise test 56 (84%) patients achieved the maximum heart rate. A Doppler spectrum enabling the measurement of TRPG following the exercise was obtained in 66 (98.5%) patients. The gradient following the exercise could not be measured in one patient with a resting TRPG of 30 mm Hg. The mean post-exercise TRPG was 40.3 ± 4.1 mm Hg (range 17-70) and the mean post-exercise increase in TRPG was 12.9 ± 8.5 mm Hg (range 2-38). A TRPG increase of 〉 20 mm Hg was found in 11 (16%) patients (including 4 patients with resting values exceeding 31 mm Hg and 7 patients with normal resting values). Twenty-one (31%) patients with echocardiographic suspicion of PH (TRPG 〉 31 mm Hg at rest and/or a post-exercise increase in TRPG of more than 20 mm Hg) were referred for RHC with 16 patients actually undergoing the procedure. Four out of these 16 patients were qualified because of the "positive" exercise echocardiography in the presence of normal TRPG values. During catheterisation arterial PH was found in 2 patients, and an excessive precapillary PAP elevation in 2 further patients. Resting venous PH was found in 1 patient and an excessive postcapillary PAP elevation at rest was demonstrated in 11 patients. CONCLUSIONS: Exercise echocardiography is a safe and useful screening tool for PH diagnosis in patients with SSc. It enables to identify patients with normal systolic PAP at rest but a significant increase during exercise. The final confirmation of PH and differentiation between precapillary arterial and postcapillary venous PH requires RHC.