Kai Mortensen

Augmentation index relates to progression of aortic disease in adults with Marfan syndrome

BACKGROUND Noninvasive applanation tonometry (APT) is useful to assess aortic stiffness and pulse wave reflection. Moreover, APT can predict outcome in many conditions such as arterial hypertension. In this study, we test whether APT measurements relate to progression of aortic disease in Marfan syndrome (MFS). METHODS We performed APT in 50 consecutive, medically treated adults with MFS (19 men and 31 women aged 32 +/- 13 years), who had not undergone previous cardiovascular surgery. During 22 +/- 16 months of follow-up, 26 of these patients developed progression of aortic disease, which we defined as progression of aortic root diameters >or=5 mm/annum (18 individuals), aortic surgery >or=3 months after APT (seven individuals), or onset of acute aortic dissection any time after APT (one individual). RESULTS Univariate Cox regression analysis suggested an association of aortic disease progression with age (P = 0.001), total cholesterol levels (P = 0.04), aortic root diameter (P = 0.007), descending aorta diameter (P = 0.01), aortic root ratio (P = 0.02), and augmentation index (AIx@HR75; P < 0.006). Multivariate Cox regression analysis confirmed an independent impact on aortic disease progression exclusively for baseline aortic root diameters (hazard ratio = 1.347; 95% confidence interval (CI) 1.104-1.643; P = 0.003) and AIx@HR75 (hazard ratio = 1.246; 95% CI 1.029-1.508; P = 0.02). In addition, Kaplan-Meier survival curve analysis illustrated significantly lower rates of aortic root disease progression both with lower AIx@HR75 (P = 0.025) and with lower pulse wave velocity (PWV) values (P = 0.027). CONCLUSIONS We provide evidence that APT parameters relate to aortic disease progression in medically treated patients with MFS. We believe that APT has a potential to improve risk stratification in the clinical management of MFS patients.

Catheter-based renal sympathetic denervation improves central hemodynamics and arterial stiffness: a pilot study.

J Clin Hypertens (Greenwich). 2012;14:861–870. ©2012 Wiley Periodicals, Inc.

Improved Heart Rate Dynamics in Patients Undergoing Percutaneous Renal Denervation

Autonomic sympathetic activation plays a key role in the pathophysiology of systemic hypertension and left ventricular hypertrophy. As shown in the Symplicity HTN-1 and HTN-2 trials, percutaneous renal denervation (PRD) has proven to be an effective and safe method to treat patients with medically resistant hypertension and is considered to influence central sympathetic tone. In patients after renal denervation, microneurography showed a gradual reduction in muscle sympathetic nerve activity in accordance with a modulation of central sympathetic tone. The effect on cardiac autonomic tone is not known. Heart rate variability (HRV) is a marker of cardiac autonomic activity. The present study assessed for the first time the effect of sympathetic renal denervation on heart rate dynamics in patients. This prospective single-center study was approved by the local ethics committee. All patients provided written informed consent. For inclusion, patients had to be older than 18 years with a systolic office blood pressure (BP) 150 mm Hg despite intake of 3 antihypertensive drugs, including one diuretic. Exclusion criteria were secondary causes of hypertension, reduced renal function (glomerular filtration rate <45 mL ⁄ min ⁄ 1.73 m), atrial fibrillation, pacemaker rhythm, and pregnancy. Patients with significant renal artery stenosis, abnormalities of renal artery anatomy, or a history of prior renal artery intervention were excluded from the study. Eligible patients had to document home BPs 3 times daily. Medication was maintained in all patients throughout follow-up and changes were made only when symptomatic low BP occurred. In 14 patients, Holter electrocardiographic recordings were analyzed for time and frequency domain HRV parameters before and 3 months after percutaneous renal sympathetic denervation. Twentyfour–hour electrocardiographic (ECG) recordings were performed using 3-channel Holter recorders (LifeCard CF, Spacelabs; Delmar Reynolds, Hertford, UK) at a sampling rate of 1024 Hz. Office BP measurements

Augmentation index and the evolution of aortic disease in marfan-like syndromes.

BACKGROUND The augmentation index at a heart rate of 75 beats/min (AIx@HR75) and central pulse pressure (CPP) can be measured noninvasively with applanation tonometry (APT). In this observational study, we investigated the relationship between AIx@HR75, CPP and aortic disease in patients with Marfan-like syndromes. METHODS We performed APT in 78 consecutive patients in whom classic Marfan syndrome (MFS) had been excluded (46 men and 32 women aged 34 +/- 13 years). These patients comprised 9 persons with MFS-like habitus, 6 with a bicuspid aortic valve (BAV), 5 with MASS phenotype, 3 with vascular type of Ehlers-Danlos syndrome (EDS), 3 with familial thoracic aortic aneurysm, 2 with Loeys-Dietz syndrome (LDS), 1 with mitral valve prolapse syndrome, 1 with familial ectopia lentis, and 48 persons with Marfan-like features but no defined syndrome. During 20 +/- 18 months after APT, we observed progression of aortic diameters in 15 patients, and aortic surgery or aortic dissection in 3 individuals. RESULTS All 11 patients with Marfan-like syndromes and progression of aortic disease exhibited AIx@HR75 > or =11%, including 8 individuals with aortic diameters < or =95th percentile of normal at baseline. Similarly, all 7 individuals without any defined syndrome but progression of aortic diameters exhibited AIx@HR75 >11%, including 6 individuals with aortic diameters < or =95th percentile at the time of APT. Aortic disease did not evolve at AIx@HR75 <11%. CPP is also related to aortic disease progression. CONCLUSIONS Aortic disease evolution relates to AIx@HR75 and CPP in Marfan like syndromes. Larger studies with comprehensive clinical and echocardiographic follow-up over long time intervals will be required to establish APT for prediction of aortic disease evolution in Marfan-like syndromes.

Successful Single-Sided Renal Denervation Approach in a Patient With Stenosis of an Accessory Renal Artery

Sympathetic overactivity has been implicated in the pathophysiology of systemic hypertension. As shown in randomized controlled trials, percutaneous renal denervation has been proven to be an effective and safe method to treat patients with resistant hypertension. In present trials, patients with significant renal artery stenosis or abnormalities in renal artery anatomy or a history of prior renal artery intervention were excluded. Thus, no data exist regarding renal denervation in patients with accessory renal artery. Here, we report a single-sided renal denervation in an 83-year-old woman (weight, 70 kg; height, 152 cm) with contralateral accessory renal artery, who experienced medically resistant hypertension despite intake of 7 antihypertensive drugs. The patient fulfilled inclusion criteria of the Symplicity HTN-1 and HTN-2 trials. Secondary causes for hypertension were excluded including sleep apnea syndrome. The patient did not have diabetes, renal failure, or coronary heart disease. The patient was required to record automated home blood pressure (BP) measurements 3 times daily for periods of 7 days before and 1 and 3 months after renal denervation. Antihypertensive medication was maintained unchanged throughout follow-up. Baseline systolic ⁄ diastolic BP was 173 22 mm Hg ⁄ 86 14 mm Hg. For renal denervation, the femoral artery was accessed in standard technique and fluoroscopic angiography was performed to visualize the renal artery. Angiography revealed normal configuration of left renal artery, where denervation was performed with application of 5 low-power radiofrequency treatments along the proximal portion of the vessel. Mean temperature was 48 3 C during 120 seconds of ablation at each point. On the right side, angiography revealed a cranial accessory renal artery with high ostial stenosis. The caudal renal artery showed a diameter of <4 mm precluding an ablation procedure. Because of a rather small renal artery diameter, stenting was not performed. In result, only left single-sided renal denervation was performed. After denervation, renal function assessed by serum creatinine was unchanged (baseline 74.9 lmol ⁄ L vs after 3 months 84.2 lmol ⁄ L). Single-sided renal denervation resulted in moderate office BP reduction 1 month after the procedure (173 22 mm Hg vs 162 20 mm Hg; not significant). Significant systolic BP changes were seen at 3 months follow-up of 14% (173 22 mm Hg vs 148 15 mm Hg; P<.001). Diastolic BP did not change significantly over time (86 14 mm Hg vs 83 9 mm Hg [1 month] and vs 83 9 mm Hg [3 months]). No adverse events were observed. Our case report supports previous data on effective and significant BP reduction after renal denervation in patients with medically resistant hypertension. We describe here for the first time successful one-sided sympathetic renal denervation in a patient with an accessory renal artery showing a relevant stenosis of the ostium. Systolic BP reduction of 25 mm Hg after 3 months was comparable to the results in the randomized Symplicity HTN-1 and HTN-2 controlled trials. However, our patient had nonsignificant changes in systolic BP after 1 month and was not affected in diastolic parameters. This observation underlines the individual response of renal denervation in patients with resistant hypertension. Accessory renal arteries originating directly from the aorta were found in 25% to 50% of normal patients at autopsy. The accessory renal arteries were often narrower than main renal arteries. There are conflicting data whether accessory renal arteries lead to systemic arterial hypertension by activation of the renin-angiotensin system as a consequence of lower perfusion pressure and higher resistance across the accessory artery. In the present case, we found an additional, significant stenosis of the accessory renal artery. The estimated incidence of accessory renal artery stenosis ranges from 1.5% in a catheter angiography study (n=68) to 2.2% in a magnetic resonance angiography study (n=45). Controversial data suggested either transcatheter angioplasty or interventional occlusion of accessory renal arteries to treat hypertension linked to this abnormality. Gupta and Tello concluded in their study that accessory renal arteries are not associated with an increased risk of hypertension development. In our patient, we performed renal denervation only on the side with normal renal anatomy and not on the side with the accessory renal artery. Also, no dilatation or stenting of the accessory renal artery stenosis was performed due to small vessel diameter. Yet, follow-up showed a significant reduction in BP. We therefore conclude that in select patients, single-sided renal denervation may be an acceptable approach to treat resistant hypertension. Furthermore, our data support the hypothesis that accessory renal arteries may not be causative for resistant hypertension.

A standardized education protocol significantly reduces traumatic injuries and syncope recurrence: an observational study in 316 patients with vasovagal syncope

AIMS The aim of this study was to assess the role of a non-pharmacological approach on the frequency of traumatic injuries and syncope recurrence in patients with vasovagal syncope and normal hearts. We report the experience in our syncope centre with a standardized education and teaching protocol for patients with vasovagal syncope. The treatment of vasovagal syncope is often complex and discouraging. Besides medical options, behaviour modification is a main component of therapy but has no statistical evidence to support its use. METHODS AND RESULTS Between January 1999 and September 2006, we prospectively enrolled all patients with vasovagal syncope. The patients were counselled about the benign nature of their disease. Specific recommendations were made according to a standardized education protocol established at our syncope centre. A pre-/post-study was conducted to investigate the effectiveness of our approach on syncope recurrence and frequency of injury as the study endpoints. Complete follow-up data were available from 85% of the study population (316 of 371) after a mean time of 710 ± 286 days (mean age 50 years; standard deviation ± 18 years, 160 female). Eighty-seven patients (27.5%) had a syncope recurrence with 22 suffering an injury during syncope. During the follow-up period, the syncope burden per month was significantly reduced from 0.35 ± 0.03 at initial presentation to 0.08 ± 0.02 (P< 0.001). The frequency of traumatic syncope was significantly lower at the time of recurrence compared with the initial presentation (25 vs. 42%; McNemars test P= 0.02). CONCLUSION A standardized education protocol significantly reduces traumatic injuries and syncope recurrence in patients with vasovagal syncope.

Should all dysfunctional high-voltage leads be extracted? Results of a single-centre long-term registry.

AIMS A considerable number of lead defects occurs during long-term cardioverter defibrillator therapy. Evidence-based strategies for the handling of chronically implanted, non-functional high-voltage (HV) leads are mandatory. METHODS AND RESULTS Patient outcome after abandonment of HV leads was retrospectively compared with patient outcome following other lead revision strategies and following primary implantation. A total of 903 consecutive patients undergoing 997 implantable cardioverter defibrillator (ICD) implantations or lead revisions were followed for a mean period of 48.8 ± 37.8 months. One or more additional HV leads were placed in 60 patients. An additional pace/sense lead was implanted in 13 patients. Extraction and replacement of a dysfunctional HV lead was performed in 21 patients. The overall rate of complications including artefact sensing, ineffective defibrillation, symptomatic subclavian vein thrombosis, and other lead defects did not differ between patients with and without an additional HV lead (10.0 vs. 8.9%, P = 0.32). Survival without lead associated complications did not differ between groups. Results remained unchanged after correction for covariates. CONCLUSIONS Abandoned HV leads did not increase the risk of ICD system-related complications in the majority of patients. Thus, a general lead extraction policy of dysfunctional HV leads cannot be advised in an average ICD population. Recommendations may not apply for young and physically active patients, in whom HV lead extraction must be considered.

Ascending aortic aneurysm and aortic valve dysfunction in bicuspid aortic valve disease

BACKGROUND The relationship of aortic valve dysfunction and ascending aortic aneurysm is unclear in adults with bicuspid aortic valve disease. METHODS We retrospectively studied 134 consecutive out-patients (98 men, 36 women aged 43 ± 18 years) with bicuspid aortic valve disease. To investigate the relationship of ascending aortic aneurysm and aortic valve dysfunction we exclusively considered severe pathologies that required treatment by surgical or percutaneous intervention. RESULTS Of 134 patients, 39 had aortic valve dysfunction without concomitant ascending aortic aneurysm which had been treated previously with isolated valve surgery or percutaneous valvuloplasty comprising 25 patients with aortic stenosis (19%) and 14 patients with aortic regurgitation (10%). Conversely, 26 patients had ascending aortic aneurysm which had been treated previously with aortic surgery (19%). Of these, ascending aortic aneurysm was associated with severe aortic stenosis in 13 patients and with severe aortic regurgitation in 7 patients, whereas aneurysm was unrelated to severe aortic valve dysfunction in the remaining 6 patients including 2 without any degree of aortic valve dysfunction. The maximal aortic diameters were similar at the time of aortic surgery irrespective of presence of severe aortic valve dysfunction (P=.527). Other characteristics of patients with ascending aortic aneurysm were also similar irrespective of presence or type of aortic valve dysfunction. CONCLUSION The majority of patients with bicuspid aortic valve disease exhibit ascending aortic aneurysm in conjunction with severe aortic valve dysfunction. However, in our study 6 of 134 (5%) of persons with bicuspid aortic valve disease developed ascending aortic aneurysm without aortic valve dysfunction.

Biphasic versus Monophasic Shock for External Cardioversion of Atrial Flutter

Background: External cardioversion is effective to terminate persistent atrial flutter. Biphasic shocks have been shown to be superior to monophasic shocks for ventricular defibrillation and atrial fibrillation cardioversion. The purpose of this trial was to compare the efficacy of rectilinear biphasic versus standard damped sine wave monophasic shocks in symptomatic patients with typical atrial flutter. Methods: 135 consecutive patients were screened, 95 (70 males, mean age 62 ± 13 years) were included. Patients were randomly assigned to a monophasic or biphasic cardioversion protocol. Forty-seven patients randomized to the monophasic protocol received sequential shocks of 100, 150, 200, 300 and 360 J. Forty-eight patients with the biphasic protocol received 50, 75, 100, 150 or 200 J. Results: First-shock efficacy with 50-Joule, biphasic shocks (23/48 patients, 48%) was significantly greater than with the 100-Joule, monophasic waveform (13/47 patients, 28%, p = 0.04). The cumulative second-shock efficacy with the 50- and 75-Joule, biphasic waveform (39/48 patients, 81%) was significantly greater than with the 100- and 150-Joule, monophasic waveform (25/47 patients, 53%, p < 0.05). The cumulative efficacy for the higher energy levels showed naturally no significant difference between the two groups. The amount of the mean delivered energy was significantly lower in the biphasic group (76 ± 39 J) compared to the monophasic one (177 ± 78 J, p < 0.05). Conclusions: For transthoracic cardioversion of typical atrial flutter, biphasic shocks have greater efficacy and the mean delivered current is lower than for monophasic shocks. Therefore, biphasic cardioversion with lower starting energies should be recommended.

Central pulse pressure and augmentation index in asymptomatic bicuspid aortic valve disease

a Centre of Cardiology and Cardiovascular Surgery, University Hospital Eppendorf, Hamburg, Germany b Department of Medical Biometry and Epidemiology, University Hospital Eppendorf, Hamburg, Germany c Medical Clinic II, University of Lubeck, Germany d Institute of Epidemiology and Social Medicine, University of Muenster, Germany e Helmholtz Zentrum Munchen, German Research Center for Environmental Health (GmbH), Institute of Epidemiology II, Neuherberg, Germany f Institute of Medical Genetics, Charite Universitatsmedizin Berlin, Germany