Ilona Michałowska

Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea

Percutaneous renal sympathetic denervation by radiofrequency energy has been reported to reduce blood pressure (BP) by the reduction of renal sympathetic efferent and afferent signaling. We evaluated the effects of this procedure on BP and sleep apnea severity in patients with resistant hypertension and sleep apnea. We studied 10 patients with refractory hypertension and sleep apnea (7 men and 3 women; median age: 49.5 years) who underwent renal denervation and completed 3-month and 6-month follow-up evaluations, including polysomnography and selected blood chemistries, and BP measurements. Antihypertensive regimens were not changed during the 6 months of follow-up. Three and 6 months after the denervation, decreases in office systolic and diastolic BPs were observed (median: −34/−13 mm Hg for systolic and diastolic BPs at 6 months; both P<0.01). Significant decreases were also observed in plasma glucose concentration 2 hours after glucose administration (median: 7.0 versus 6.4 mmol/L; P=0.05) and in hemoglobin A1C level (median: 6.1% versus 5.6%; P<0.05) at 6 months, as well as a decrease in apnea-hypopnea index at 6 months after renal denervation (median: 16.3 versus 4.5 events per hour; P=0.059). In conclusion, catheter-based renal sympathetic denervation lowered BP in patients with refractory hypertension and obstructive sleep apnea, which was accompanied by improvement of sleep apnea severity. Interestingly, there are also accompanying improvements in glucose tolerance. Renal sympathetic denervation may conceivably be a potentially useful option for patients with comorbid refractory hypertension, glucose intolerance, and obstructive sleep apnea, although further studies are needed to confirm these proof-of-concept data.

Clinical characteristics of patients with resistant hypertension: the RESIST-POL study.

Recent studies indicate that resistant hypertension (RHTN) is present in about 12% of the treated hypertensive population. However, patients with true RHTN (confirmed out of the office) have not been widely studied. We prospectively studied 204 patients (123 male, 81female, mean age 48.4 years, range 19–65 years) with truly RHTN (ambulatory daytime mean blood pressure >135/85 mm Hg). We evaluated the frequency of obstructive sleep apnea (OSA), renal artery stenosis (RAS), primary aldosteronism (PA) and other secondary forms of hypertension (HTN) and conditions. Mild, moderate and severe OSA were present in 55 (27.0%), 38 (18.6%) and 54 (26.5%) patients, respectively. Secondary forms of HTN were diagnosed in 49 patients (24.0%), the most frequent being PA (15.7%) and RAS (5.4%). Metabolic syndrome (MS) was present in 65.7% of patients. Excessive sodium excretion was evident in 33.3% of patients and depression in 36.8% patients. In patients with RHTN, OSA and MS were the most frequent conditions, frequently overlapping with each other and also with PA. Our data indicate that in the vast majority of patients with truly RHTN, at least one of three co-morbidities—OSA, MS and PA—is present. Other conditions, even though less frequent, should also be taken into the consideration.

Relationship between renal resistive index and early target organ damage in patients with never treated essential hypertension

The aim of our study was to evaluate renal resistive index (RI) value in never treated hypertensive patients in relation to ambulatory blood pressure measurement (ABPM) values and early target organ damage. The study included 318 subjects: 223 patients with never treated essential hypertension (mean age 37.1 years) and 95 normotensive healthy subjects (mean age 37.9 years). ABPM, echocardiography and carotid and renal arteries duplex color Doppler examinations were performed. RI values in patients with never treated essential hypertension were no different from the normotensive control group (0.59 ± 0.05 vs 0.59 ± 0.05; NS). In the untreated patients RI correlated significantly with 24‐h pulse pressure (r=0.234; p<0.01) and ambulatory arterial stiffness index (AASI) values (r=0.274; p<0.001), intima‐media thickness (IMT) (r=0.249; p<0.001), E′/A′ (rho= −0.279; p<0.001) and relative wall thickness (RWT; r=0.185; p<0.01). In the multivariate stepwise analysis, RI values correlated independently with carotid IMT (β=0.272; p=0.020) and 24‐h AASI values (β=0.305; p=0.009). In normotensive healthy controls, significant independent correlation between RI and carotid IMT and 24‐h AASI values were also found. Our study may indicate limited value of RI in differentiating patients with uncomplicated hypertension with healthy controls. Renal resistive values were independently correlated with carotid IMT and AASI. These may suggest that renal vascular resistance is related to two markers for cardiovascular events both in the hypertensive and normotensive subjects.

Prognostic value of renal fractional flow reserve in blood pressure response after renal artery stenting (PREFER study)

BACKGROUND The aim of our study was to determine a potential relationship between resting translesional pressures ratio (Pd/Pa ratio), renal fractional flow reserve (rFFR) and blood pressure response after renal artery stenting. METHODS Thirty five hypertensive patients (49% males, mean age 64 years) with at least 60% stenosis in angiography, underwent renal artery stenting. Translesional systolic pressure gradient (TSPG), Pd/Pa ratio (the ratio of mean distal to lesion and mean proximal pressures) and hyperemic rFFR - after intrarenal administration of papaverine - were measured before stent implantation. Ambulatory blood pressure measurements (ABPM) were recorded before the procedure and after 6 months. The ABPM results were presented as blood pressure changes in subgroups of patients with normal (≥ 0.9) vs. abnormal (< 0.9) Pd/Pa ratio and normal (≥ 0.8) vs. abnormal (< 0.8) rFFR. RESULTS Median Pd/Pa ratio was 0.84 (interquartile range 0.79-0.91) and strongly correlated with TSPG (r = -0.89, p < 0.001), minimal lumen diameter (MLD; r = 0.53, p < 0.005) and diameter stenosis (DS; r = -0.51, p < 0.005). Median rFFR was 0.78 (0.72-0.82). Similarly, significant correlation between rFFR and TSPG (r = -0.86, p < 0.0001), as well as with MLD (r = 0.50, p < 0.005) and DS (r = -0.51, p < 0.005) was observed. Procedural success was obtained in all patients. Baseline Pd/Pa ratio and rFFR did not predict hypertension response after renal artery stenting. Median changes of 24-h systolic/diastolic blood pressure were comparable in patients with abnormal vs. normal Pd/Pa ratio (-4/-3 vs. 0/2 mm Hg; p = NS) and with abnormal vs. normal rFFR (-2/-1 vs. -2/-0.5 mm Hg, respectively). CONCLUSIONS Physiological assessment of renal artery stenosis using Pd/Pa ratio and papaverine- induced renal fractional fl ow reserve did not predict hypertension response after renal artery stenting.

Assessment of renal artery stenosis using both resting pressures ratio and fractional flow reserve – Relationship to angiography and ultrasonography

Abstract Background. Clinical benefit from renal artery revascularization remains controversial, probably because of inaccurate stenosis severity assessment. Objective. The aim of the study was to evaluate resting translesional pressures ratio and renal fractional flow reserve (rFFR) in relation to angiography and Doppler duplex ultrasonography in patients with at least moderate renal artery stenosis (RAS). Methods. 44 hypertensive patients (48% of males, mean age 65 years) with at least moderate RAS were investigated. Translesional systolic pressure gradient (TSPG), resting Pd/Pa ratio (the ratio of mean distal to lesion and mean proximal pressures) and hyperemic rFFR – after intrarenal administration of papaverine – were evaluated. Quantitative angiographic analysis of stenosis severity was performed including minimal lumen diameter (MLD) and percent diameter stenosis (DS) assessment. Renal/aortic ratio (RAR), resistive index (RI) and deltaRI (side-to side difference) were obtained in Doppler-duplex ultrasonography. The predictive value of selected variables was calculated using receiver-operating characteristics curves. Results. Mean Pd/Pa ratio was 0.86 ± 0.12 and decreased to 0.79 ± 0.13 after papaverine administration. Both Pd/Pa ratio and rFFR strongly correlated with TSPG (r = −0.92, p < 0.0001 and r = −0.88, p < 0.0001, respectively) and moderately with MLD (r = 0.62, p < 0.0001 and r = 0.66, p < 0.0001) and DS (r = −0.63, p < 0.0001 and r = −0.70, p < 0.0001). To identify more than 70% RAS, considered severe, the most predictive cut-off values were 0.93 for Pd/Pa ratio and 0.80 for rFFR. Conclusions. Mean Pd/Pa ratio and rFFR strongly correlated with angiographic data and in less pronounced manner with ultrasound parameters reflecting intrarenal blood flow. The best accuracy cut-off points for severe RAS predicting were 0.93 and 0.80, respectively.

Relationship between hemodynamic parameters of renal artery stenosis and the changes of kidney function after renal artery stenting in patients with hypertension and preserved renal function

Abstract Introduction: The role of physiological assessment of renal artery stenosis (RAS) using renal fractional flow reserve (rFFR) and resting translesional pressures ratio (Pd/Pa ratio) in the prediction of benefit from revascularization is still unknown. Objectives: The aim of the study was to assess the relationship between hemodynamic data and the change in kidney function after renal artery stenting in secondary hypertension. Patients and methods: 34 hypertensive patients (50% males, median age 65 years) with at least 60% RAS, underwent stenting and were followed up for 6 months. Pd/Pa ratio (ratio of mean distal to lesion to proximal pressure) and hyperemic rFFR (after papaverine) were measured before the procedure. At baseline and after 6 months, the glomerular filtration rate (eGFR), serum cystatin C and albuminuria were determined. In receiver operating characteristic curves, two previously established cut-off values with the highest accuracy of identifying severe RAS were used: 0.93 for the Pd/Pa ratio and 0.8 for the rFFR. Results: No significant difference in eGFR was found between patients with decreased and normal Pd/Pa ratio (1.4 vs 7.9 ml/min, p = ns). Similarly, minor changes in eGFR were observed in patients with decreased vs normal rFFR (2.4 vs 4.1 ml/min, p = ns). In patients with decreased Pd/Pa ratio, albuminuria remained stable (change 1.4 mg/24 h) compared with an increase of 12.6 mg/24 h in the subgroup with Pd/Pa ≥ 0.93(p < 0.05). However, after exclusion of two outliers with significant baseline proteinuria (425 and 1095 mg/24 h, respectively), the difference in albuminuria change according to the baseline Pd/Pa ratio was no longer maintained. Conclusions: Hemodynamic parameters of RAS do not distinguish the patients who may benefit from renal artery stenting in terms of kidney function improvement in short-term follow-up. Trial registration: ClinicalTrials.gov identifier: NCT01128933.

Transcatheter aortic valve implantation in patients with bicuspid aortic valve: a series of cases

BACKGROUND Bicuspid aortic valve (BAV) has been considered a relative contraindication for transcatheter aortic valve implantation (TAVI). Due to more oval shape of the BAV annulus compared to tricuspid aortic valve, the procedure has been discouraged because of an increased risk of stent assembly displacement, uneven expansion, post-procedure paravalvular leakage, stent valve distortion, or other malfunction after implantation. For the same reasons patients with BAV have been excluded from the majority of clinical TAVI trials. AIM To evaluate the efficacy and safety of TAVI in patients with BAV stenosis. METHODS We analysed a group of 104 patients admitted to our institution for TAVI between January 2009 and May 2012. During pre-procedure evaluation, transthoracic and transoesophageal (TEE) echocardiography as well as angio-computed tomography (CT) scan were performed to assess aortic valve anatomy and morphology. Appropriate measurements and detailed analyses of imaging data have been accomplished to select optimal access site, prosthesis size as well as to plan the procedure. BAVs were recorded in seven patients (6.7%; mean age 77.7 years). These patients presented with severe symptomatic aortic valve stenosis with a mean aortic valve area of 0.55 cm² (0.46-0.7 cm²) as measured in TEE. All of the patients had been disqualified from surgical valve replacement due to high surgical risk with a mean logistic Euroscore of 19.9%. All of them successfully underwent TAVI using CoreValve (n = 5) or Sapien (n = 2) valves. Follow-up was completed at 30 days, and six and 12 months after the procedure. RESULTS During follow-up one patient developed an elliptic distortion of the aortic prosthesis in CT, although it did not result in significant malfunctioning of the implant. One patient died of infective endocarditis 30 days after the procedure. Survivors at 30-day follow-up had mild to moderate aortic insufficiency, and it did not deteriorate after six months. At one year follow-up six out of seven patients remained alive. They achieved significant functional improvement by New York Heart Association class compared to baseline. CONCLUSIONS TAVI may constitute an alternative treatment option for high-risk patients with BAV, resulting in a low periprocedural mortality rate, and good 30-day, six-month, and one-year outcomes.

22-Year-old patient with malignant hypertension associated with primary aldosteronism

A 22-year-old male patient with no known history of hypertension was admitted to the emergency unit of the regional hospital in March 2011 with signs of pulmonary oedema and was found to have blood pressure (BP) of 220/140 mm Hg. Before hospitalization the patient reported progressive shortness of breath for 2 days. His BP was reduced by oral administration of captopril within few hours to 170/100 mm Hg. In addition, the patient was put on amlodipine 20 mg per day and bispoprolol 10 mg per day. After the patient was stabilized, he was transferred to the Department of Hypertension, Institute of Cardiology, Warsaw.

Usefulness of Somatostatin Receptor Scintigraphy (99mTc-[HYNIC, Tyr3]-Octreotide) and 123I-Metaiodobenzylguanidine Scintigraphy in Patients with SDHx Gene-Related Pheochromocytomas and Paragangliomas Detected by Computed Tomography

Aims: The aim of this study was to assess the usefulness of somatostatin receptor scintigraphy (SRS) using 99mTc-[HYNIC, Tyr3]-octreotide (TOC) and 123I-metaiodobenzylguanidine (mIBG) in patients with SDHx-related syndromes in which paragangliomas were detected by computed tomography and to establish an optimal imaging diagnostic algorithm in SDHx mutation carriers. Methods: All carriers with clinical and radiological findings suggesting paragangliomas were screened by SRS and 123I-mIBG. Lesions were classified by body regions, i.e. head and neck, chest, abdomen with pelvis and adrenal gland as well as metastasis. Results: We evaluated 46 SDHx gene mutation carriers (32 index cases and 14 relatives; 28 SDHD, 16 SDHB and 2 SDHC). In this group, 102 benign tumors were found in 39 studied patients, and malignant disease was diagnosed in 7 patients. In benign tumors, the sensitivity of SRS was estimated at 77% and of 123I-mIBG at 22.0%. The SRS and mIBG sensitivity was found to be clearly region dependent (p < 0.001). The highest SRS sensitivity was found in head and neck paragangliomas (HNP; 91.4%) and the lowest was found in abdominal paragangliomas and pheochromocytomas (40 and 42.9%, respectively). The highest 123I-mIBG sensitivity was found in pheochromocytomas (sensitivity of 100%) and the lowest in HNP (sensitivity of 3.7%). In metastatic disease, SRS was superior to mIBG (sensitivity of 95.2 vs. 23.8%, respectively). Conclusion: SRS and 123I-mIBG single photon emission computed tomography (SPECT) sensitivity in SDHx patients is highly body region dependent. In malignant tumors, SRS is superior to 123I-mIBG SPECT.

GROWTH RATE OF PARAGANGLIOMAS RELATED TO GERMLINE MUTATIONS OF THE SDHX GENES

OBJECTIVE The purpose was to determine the growth rate of succinate dehydrogenase subunit (SDHx) gene-related paragangliomas based on computed tomography (CT) measurements. METHODS Twenty-seven patients with SDHx mutations who underwent subsequent CT examinations were enrolled in the study. Tumors were classified as head and neck (HNP), thoracic, or abdominal/pelvic paragangliomas (PGLs). The percentage volume increase and volume doubling time were estimated. RESULTS We analyzed 56 PGLs (21 with SDHD, 6 with SDHB mutations) in 27 patients (16 men, 11 women; mean age 37.7 years). The estimated median of the follow-up was 23 months. Twenty-two (39.3%) PGLs were located in the abdomen, 8 (14.3%) in the thorax, and 26 (46.4%) in the head and neck region. The median volume growth rate was estimated at 10.4% per year (interquartile range [IQR]: -1.3; 36.3). The volume doubling time was estimated as 7.01 (2.24;+∞) years. By tumor site, the estimated medians of the annual volume growth rates were 13.6% (IQR:0.8 -30.4) for HNP, -6.06% (IQR: -1.79;47.32) for thoracic PGLs, and 10.5% (IQR: -2.2;44.6) for abdominal PGLs. The volume doubling time was 5.44 years (2.61; 87.0) for HNP, 11.8 years (1.79;+∞) for thoracic PGLs, and 6.94 years (1,88;+∞) for abdominal PGLs. There was no significant difference in the volume growth rate according to tumor location or initial size (P>.7 and P = .07, respectively) or gene mutation type (SDHB vs. SDHD, P>.8). CONCLUSION PGLs related to SDHx mutations are slowly growing tumors. There were no correlations between tumor location, growth rate or initial size over a 23-month follow-up period. ABBREVIATIONS CT = computed tomography HNP = head and neck paraganglioma IQR = interquartile range PGL = paraganglioma PPGL = pheochromocytoma and paraganglioma SDH = succinate dehydrogenase.