Risk assessment in patients with symptomatic and asymptomatic pre-excitation.

AIMS: Controversy remains as to whether the exercise stress test (EST) is sufficient for risk evaluation in patients with pre-excitation. This study aims to clarify the usefulness of EST in risk stratification in both asymptomatic and symptomatic patients presenting with pre-excitation. METHODS AND RESULTS: This prospective study includes consecutive asymptomatic and symptomatic patients with pre-excitation referred for risk assessment. All participants performed an incremental EST (bicycle) prior to an electrophysiology study (EPS). Primary data from the EST included loss of pre-excitation during exercise, and primary data from the EPS included the measurement of accessory pathway effective refractory period (APERP), shortest pre-excited RR interval (SPERRI), and inducible arrhythmia with the use of a beta-adrenergic receptor agonist if deemed necessary. One hundred and sixty-four patients (59 asymptomatic, 105 symptomatic) completed an EST and EPS. Forty-five patients (27%) demonstrated low-risk findings on EST, of which 19 were asymptomatic and 26 were symptomatic. Six patients with low-risk EST findings had SPERRI/APERP ≤ 250 ms at EPS, and two of them were asymptomatic. The sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy of low-risk EST for excluding patients with SPERRI/APERP ≤ 250 ms were 40, 91, 87, 51, and 60%, respectively. The number of patients with inducible arrhythmia at EPS was similar in the asymptomatic (36, 69%) and symptomatic (73, 61%) groups. CONCLUSION: Sudden loss of pre-excitation during EST has a low NPV in excluding high-risk APs. The EPS with the use of isoproterenol should be considered to accurately assess the risk of patients with pre-excitation regardless of symptoms (ClinicalTrials.gov Identifier: NCT03301935).

Association between catheter ablation of atrial fibrillation and mortality or stroke.

OBJECTIVE: Catheter ablation of atrial fibrillation effectively reduces symptomatic burden. However, its long-term effect on mortality and stroke is unclear. We investigated if patients with atrial fibrillation who undergo catheter ablation have lower risk for all-cause mortality or stroke than patients who are managed medically. METHODS: We retrospectively included 5628 consecutive patients who underwent first-time catheter ablation for atrial fibrillation between 2008 and 2018 at three major Swedish electrophysiology units. Control individuals with an atrial fibrillation diagnosis but without previous stroke were selected from the Swedish National Patient Register, resulting in a control group of 48 676 patients. Propensity score matching was performed to produce two cohorts of equal size (n=3955) with similar baseline characteristics. The primary endpoint was a composite of all-cause mortality or stroke. RESULTS: Patients who underwent catheter ablation were healthier (mean CHA2DS2-VASc score 1.4±1.4 vs 1.6±1.5, p<0.001), had a higher median income (288 vs 212 1000 Swedish krona [KSEK]/year, p<0.001) and had more frequently received university education (45.1% vs 28.9%, p<0.001). Mean follow-up was 4.5±2.8 years. After propensity score matching, catheter ablation was associated with lower risk for the combined primary endpoint (HR 0.58, 95% CI 0.48 to 0.69). The result was mainly driven by a decrease in all-cause mortality (HR 0.51, 95% CI 0.41 to 0.63), with stroke reduction showing a trend in favour of catheter ablation (HR 0.75, 95% CI 0.53 to 1.07). CONCLUSIONS: Catheter ablation of atrial fibrillation was associated with a reduction in the primary endpoint of all-cause mortality or stroke. This result was driven by a marked reduction in all-cause mortality.

Validation of diagnostic accuracy of a handheld, smartphone-based rhythm recording device.

AIM: Evaluation of the diagnostic accuracy of a rhythm recording device, for detection of atrial tachyarrhythmia (ATA) and atrial fibrillation (AF) compared to 12-lead-electrocardiogram (12-L-ECG). RESEARCH DESIGN AND METHODS: Two hundred 12-L-ECGs (reference standard) and Coala Heart Monitor (CHM) recordings (index test) were collected from 189 patients. Two electrophysiologists independently performed manual analysis of all 12-L-ECGs and CHM recordings in random order. The CHM recordings were also analyzed by an automatic algorithm and compared to the results of the reference standard. RESULTS: Manual analysis of CHM for ATA showed a sensitivity of 98.9% (95% confidence interval (CI): 94.0-100) and a specificity of 100% (CI: 96.6-100). Manual analysis for AF had a sensitivity of 100% (CI: 95.3-100) and a specificity of 97.5% (CI: 93.0-99.5). Automatic analysis for ATA showed a sensitivity of 93.5% (CI: 86.3-97.6) and a specificity of 92.6% (CI: 85.9-96.7). Automatic analysis for AF showed a sensitivity of 97.4% (CI: 91.0-99.7) and a specificity of 86.1% (CI: 78.6-91.7). CONCLUSION: CHM has a very high accuracy for ATA and AF in manual analysis and a high accuracy for ATA and AF in automatic analysis, making the device suitable for screening.

Electrical cardioversion for early recurrences post pulmonary vein isolation.

BACKGROUND: To study the association between timing and success of electrical cardioversion (ECV) for the treatment of early recurrences (ERs) of atrial fibrillation post pulmonary vein isolation (PVI) on long-term rhythm outcome. METHODS: Data of 133 patients ablated for paroxysmal or persistent atrial fibrillation receiving ECV for ERs, i.e., atrial tachyarrhythmia recurrences within 90 days post ablation were analyzed. During 1-year follow-up, patients were screened for late recurrences (LRs), i.e., recurrences after the blanking period. RESULTS: In 114 patients (85.7%), ECV was successful compared to 19 patients (14.3%) with failed ECV. A higher body mass index (odds ratio (OR) 1.19 (95% CI 1.02-1.39), p = 0.029), a lower left ventricular ejection fraction (OR 1.07 (95% CI 0.99-1.15), p = 0.079), and performance of ECV > 7 days from ER onset (OR 2.99 (95% CI 1.01-8.87), p = 0.048) remained independently associated with ECV failure. During 1-year follow-up, the rate of LR was significantly higher among patients with failed ECV as compared to patients with successful ECV (hazard ratio (HR) 3.00 (95% CI, 1.79-5.03), p < 0.001). Patients with ECV performed > 7 days from ER onset had a significantly higher risk of developing LR as compared to patients with ECV performed within ≤ 7 days from ER onset (HR 1.73 (95% CI 1.15-2.62), p = 0.009). Performance of ECV > 7 days from ER onset (HR 1.76 (95% CI 1.16-2.67), p = 0.008) and failed ECV (HR 3.32 (95% CI 1.96-5.64), p < 0.001) remained independently associated with LR. CONCLUSIONS: A failed ECV and performance of ECV > 7 days from ER onset were independently associated with LR.

Transseptal Access Through an Atrial Septal Defect Closure Device Resulting in Open Heart Surgery.

A pulmonary vein isolation procedure in a patient with an atrial septal defect (ASD) closure device was complicated by entrapment of a mapping catheter in the device. The procedure was converted to open heart surgery, the device with the trapped catheter was explanted, the ASD was covered with a bovine patch, and a cryomaze procedure was performed. (Level of Difficulty: Intermediate.).

Color Variations in Left Atrial Appendage Occluders.

The authors stopped a case of left atrial appendage occlusion because of miscolored brownish devices. The investigation demonstrated that devices may show a range of colors from a typical blue to a brownish hue, depending on oxide layer thickness, and this does not appear to have any impact on the performance of the device. (Level of Difficulty: Intermediate.).

Cryoablation of atypical atrioventricular nodal reentry tachycardia.

AIM: Data on ablation for atypical recurrent atrioventricular nodal reentry tachycardia (AVNRT) and long-term follow-up are generally sparse. Furthermore, the rate of recurrence and safety of cryoablation for atypical AVNRT has not been established. We compared patients cryoablated for atypical AVNRT and typical AVNRT during long-term follow-up. METHODS: All patients (n = 2612) who underwent catheter ablation for AVNRT at the Karolinska University Hospital between January 2009 and August 2019 were analyzed. A total of 91 patients undergoing first-time cryoablation for atypical AVNRT were included. A control group with first-time cryoablation for typical AVNRT was matched in a 1:1 ratio. Patients were followed-up for recurrences for a median of 5.0 years (interquartile range: 3.1-7.5 years). RESULTS: After 5 years, AVNRT recurrence occurred in 10 patients (11.0%) in the atypical AVNRT group and in 8 patients (8.8%) in the typical AVNRT group (hazard ratio: 1.31 [95% confidence interval: 0.52-3.32]; p = 0.568). The duration of the index procedure was significantly longer for atypical compared to typical AVNRT ablation (132.1 ± 49.2 min vs. 110.1 ± 38.8 min; p = 0.001). Transient AV blocks occurred in a similar fashion in the atypical compared to typical group (11 [12.1%] vs. 4 [4.9%]; p = 0.103). However, no ablation induced persistent AV block developed in either group. CONCLUSION: Cryoablation for atypical AVNRT showed similar rate of recurrences and safety compared to typical AVNRT during long-term follow-up.

Low incidence of major complications after the first six hours post atrial fibrillation ablation: Is same-day discharge safe and feasible in most patients?

AIMS: This study evaluates the incidence of procedural complications related to catheter ablation of atrial fibrillation (AF) to assess the potential feasibility and safety of same-day discharge in a large cohort. METHODS: We performed an analysis of prospectively collected data of complications of all patients staying overnight after undergoing AF ablation between 2001 and 2020 at a tertiary center. Using medical records, we analyzed complications occurring intraprocedurally until 6 h postablation and between 6 h postablation and discharge the day after the ablation procedure. RESULTS: In 5414 AF ablations, we identified a total of 108 (2.0%) major complications occurring intraprocedural or before discharge. Most major complications occurred intraprocedurally or within 6 h after the procedure (n = 96, 1.8%). Twelve (0.2%) major complications occurred between 6 h Postablation and discharge. The most common of these major complications were congestive heart failure (n = 6) and transient ischemic attack (TIA, n = 4). During this time span, 61 (1.1%) minor complications occurred. Factors independently associated with major complications intraprocedurally and until discharge were body mass index (BMI) ≥ 30 kg/m2 (p = .009), significant valvular disease (p = .001), cardiomyopathy (p < .001), prior stroke or TIA (p = .014), first-time procedure versus repeat procedure (p = .013), cryoablation versus radiofrequency (p < .001), and procedure duration (p < .001). CONCLUSION: After AF ablation, very few complications occurred between 6 h postprocedure and discharge the next day. Therefore, same-day discharge is a safe option for a majority of patients.

Sinus heart rate post pulmonary vein ablation and long-term risk of recurrences.

PURPOSE: Cather ablation is known to influence the autonomic nervous system. This study sought to investigate the association of sinus heart rate pre-/post-ablation and recurrences in patients with atrial fibrillation undergoing pulmonary vein isolation (PVI). METHODS: Between January 2012 and December 2017, data of 482 patients undergoing their first PVI were included. Sinus heart rate was recorded before (PRE), directly post-ablation (POST) and 3 months post-ablation (3 M). All patients were screened for atrial tachyarrhythmia recurrences during the one-year follow-up. RESULTS: In the total study cohort, the mean resting sinus heart rate at PRE [mean 57.9 bpm (95% CI 57.1-58.7 bpm)] increased by over 10 bpm to POST [mean 69.4 bpm (95% CI 68.5-70.3 bpm); p < 0.001] followed by a slight decrease at 3 M [mean 67.3 bpm (95% CI 66.4-68.2 bpm)] but still remaining higher compared to PRE (p < 0.001). This pattern was observed in patients with and without recurrences at POST and 3 M (both p < 0.001 compared to PRE). However, at 3 M the mean sinus heart rate was significantly lower in patients with compared to patients without recurrences (p = 0.031). In this regard, patients with a heart rate change < 11 bpm (PRE to 3 M) or, as an alternative parameter, patients with a heart rate < 60 bpm at 3 M had a significantly higher risk of recurrences compared to the remaining patients (Hazard ratio (HR) 1.82 (95% CI 1.32-2.49), p < 0.001 and HR 1.64 (95% CI 1.20-2.25), p = 0.002, respectively). CONCLUSION: Our study confirms the impact of PVI on cardiac autonomic function with a significant sinus heart rate increase post-ablation. Patients with a sinus heart rate change < 11 bpm (PRE to 3 M) are at higher risk for recurrences during one-year post-PVI.

Focal atrial tachycardia-the localization differences between men and women: A study of 487 consecutive patients.

OBJECTIVE: The preferential sites for focal atrial tachycardia (FAT) are mainly in the right atrium in both sexes. However, a limited number of studies have indicated that sex differences in the localization of FAT. This study investigated possible sex differences in the distribution of FAT in a large cohort of patients referred for ablation. METHODS: From 2004 to 2019, 487 patients (298 women) were referred to our institution for ablation of FAT. A standard electrophysiological study was conducted, and isoproterenol or atropine was given when needed. Conventional catheter mapping, electroanatomic contact mapping, and noncontact mapping were used to assess the origin of ectopic atrial tachycardia. RESULTS: Overall, 451 foci were successfully ablated in 436 patients (90%). Although the foci located along the crista terminalis were more common in women than in men (42% vs. 29%; p=0.023), the opposite were found in the foci located along the tricuspid annulus (5% vs. 11%; p=0.032) and the right atrial appendage (RAA) (1% vs. 3%; p=0.032). Other locations were similarly distributed in men and women. In addition, the presence of persistent FAT was more frequent in men than in women (22% vs. 5%; p<0.001). Finally, the difference in the induction pattern of FAT was also remarkable between sexes. CONCLUSION: The distribution of FAT in women and men is different. In addition, persistent FAT seems more often in men than in women. The different distribution, persistency, and induction pattern of FAT should be considered in the successful management of this type of tachycardia.

Long-term outcome of patients with invasive electrophysiology procedure-related cardiac tamponade.

AIMS: Iatrogenic cardiac tamponades are a rare but dreaded complication of invasive electrophysiology procedures (EPs). Their long-term impact on clinical outcomes is unknown. This study analysed the risk of death or serious cardiovascular events in patients suffering from EP-related cardiac tamponade requiring pericardiocentesis during long-term follow-up. METHODS AND RESULTS: Out of 19 997 invasive EPs at the Karolinska University Hospital between January 1998 and September 2018, all patients with EP-related periprocedural cardiac tamponade were identified (n = 60) and matched (1:3 ratio) to a control group (n = 180). After a follow-up of 5 years, the composite primary endpoint - death from any cause, acute myocardial infarction, transitory ischaemic attack (TIA)/stroke, and hospitalization for heart failure - occurred in significantly more patients in the tamponade than in the control group [12 patients (20.0%) vs. 19 patients (10.6%); hazard ratio (HR) 2.53 (95% confidence interval, CI 1.15-5.58); P = 0.021]. This was mainly driven by a higher incidence of TIA/stroke in the tamponade than in the control group [HR 3.75 (95% CI 1.01-13.97); P = 0.049]. Death from any cause, acute myocardial infarction, and hospitalization for heart failure did not show a significant difference between the groups. Hospitalization for pericarditis occurred in significantly more patients in the tamponade than in the control group [HR 36.0 (95% CI 4.68-276.86); P = 0.001]. CONCLUSION: Patients with EP-related cardiac tamponade are at higher risk for cerebrovascular events during the first 2 weeks and hospitalization for pericarditis during the first months after index procedure. Despite the increased risk for early complications tamponade patients have a good long-term prognosis without increased risk for mortality or other serious cardiovascular events.

Early recurrences of atrial tachyarrhythmias post pulmonary vein isolation.

AIMS: To investigate the significance of early recurrence (ER) of atrial tachyarrhythmias after pulmonary vein isolation (PVI) on the development of late recurrence (LR) and to redefine the blanking period during which an ER is considered nonspecific. METHODS: Data of 713 patients undergoing their first PVI for paroxysmal or persistent atrial fibrillation between January 2012 and December 2017 were included. All patients were followed-up for 12 months according to clinical and outpatient routine and were screened for any atrial tachyarrhythmia lasting >30 seconds occurring during the first 3 months postablation (ER) and after the 3 months blanking period (LR). RESULTS: Patients with ER compared to those without ER had significantly more LR (74.5% vs 16.5% vs, P < .001). The occurrence of ER during the first, second and third months showed increasing LR rates of 35.2%, 67.9%, and 94.8%, respectively (P < .001). Receiver operator characteristic analysis revealed a blanking period of 46 days with the highest sensitivity (68.1%) and specificity (96.5%). Later timing and longer time span of ER were independent predictors for LR in multivariable analysis. CONCLUSION: ER is a strong predictor for LR. Our study advocates a shortening of the post-PVI blanking period followed by a "gray zone" up to 3 months where individualized therapeutic decisions based on additional risk factors should be considered. We suggest that the ER time span might serve as such a predictor identifying patients at the highest risk for LR.

Safety of fluoroscopy-guided transseptal approach for ablation of left-sided arrhythmias.

AIMS: The transseptal approach is used for left atrial access during the ablation of atrial fibrillation (AF) and other left-sided arrhythmia substrates. Transseptal puncture (TP) is commonly performed with fluoroscopic guidance, contrast injection, and pressure monitoring. In many centres, additional techniques [intracardiac echocardiography (ICE), transoesophageal echocardiography (TEE), radiofrequency needle] are used to facilitate TP but its use adds costs. In this retrospective study, we studied the safety and complication rate when TP was routinely done with fluoroscopic guidance, contrast injection, and pressure monitoring using ICE or TEE only in selected cases. METHODS AND RESULTS: This study analysed 4690 consecutive TP performed between 2000 and 2015: 3408 (72.6%) were ablation of AF, left-sided atrial flutter, or left-sided atrial tachycardia (non-AP group); 1153 (24.6%) were ablation of left-sided accessory pathway, AP group; and 129 (2.8%) were ablation of ventricular tachycardia. Transseptal puncture was done under fluoroscopy, pressure monitoring, and commonly using contrast media injection. In 27 procedures, ICE or TEE was used to guide the TP. We found 34 tamponades (Tx) that required pericardial drainage of which 28 (0.59%) could possibly be TP related and six could not. The total complication rate for all Tx was 0.72%. A higher rate of tamponades was observed in the AF (non-AP) group than in the AP group (0.88 vs. 0.17%, P < 0.02). The highest rate of tamponades was registered during the operators 51-100 cases, 1.3%, and decreased to 0.4% in cases 101-200, P = 0.04. CONCLUSION: TP can safely be done under fluoroscopy and pressure monitoring without routine use of additional techniques. With experience, operators should be able to further decrease complication rate.

Hypertension is associated with increased mortality in patients with ischaemic heart disease after revascularization with percutaneous coronary intervention - a report from SCAAR.

BACKGROUND: The prognostic role of hypertension on long-term survival after percutaneous coronary intervention (PCI) is limited and inconsistent. We hypothesize that hypertension increases long-term mortality after PCI. METHODS: We analyzed data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) for all consecutive patients admitted coronary care units in Sweden between January 1995 and May 2013 and who underwent PCI due to ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI)/unstable angina (UA) or stable angina pectoris. We used Cox proportional-hazards regression for statistical modelling on complete-case data as well as on imputed data sets. We used interaction test to evaluate possible effect-modulation of hypertension on risk estimates in several pre-specified subgroups: age categories, gender, diabetes, smoking and indication for PCI (STEMI, NSTEMI/UA and stable angina). RESULTS: During the study period, 175,892 consecutive patients underwent coronary angiography due to STEMI, NSTEMI/UA or stable angina. 78,100 (44%) of these had hypertension. Median follow-up was 5.5 years. After adjustment for differences in patient's characteristics, hypertension was associated with increased risk for mortality (HR 1.12, 95% CI 1.09-1.15, p < .001). In subgroup analysis, risk was highest in patients less than 65 years, in smokers and in patients with STEMI. The risk was lowest in patients with stable angina (p < .001 for interaction test). CONCLUSION: Hypertension is associated with higher mortality in patients with STEMI, NSTEMI/UA or stable angina who are treated with PCI.

Histone deacetylase inhibition enhances tissue plasminogen activator release capacity in atherosclerotic man.

UNLABELLED: The expression of the tissue plasminogen activator (t-PA) gene appears to be under epigenetic control and can be affected by histone deacetylation inhibition. The study aimed to test if histone deacetalyase inhibitor treatment lead to increased t-PA release or reduced exhaustion in t-PA release in response to stimulation, as well as change in plasminogen activator inhibitor-1 (PAI-1) in subjects with coronary disease. In this clinical study, 16 post-myocardial infarction subjects, the perfused forearm model was used with isoprenaline provocation during 20 minutes, to stimulate local t-PA release. Each subject was measured twice on the same day (repeated stimuli sequences) as well as on two different occasions, without treatment and after four weeks of treatment with valproic acid (500 mg, twice daily). Net forearm release for t-PA in response to isoprenaline at minutes 1.5, 3, 6, 9, 12, 15 and 18 was measured, allowing assessment of cumulative t-PA release. There was a reduction in the exhaustion of cumulative t-PA release during repeated and prolonged stimulation with valproic acid treatment compared to non-treatment. Plasma PAI-1 antigen was decreased following treatment compared to non-treatment (18.4 ± 10.0 vs. 11.0 ± 7.1 nanograms/ml respectively, mean with 95% confidence interval). These findings demonstrate that histone deacetylation inhibition increases the capacity for endogenous t-PA release in subjects with vascular disease. Furthermore, the fibrinolytic balance is favored with suppressed PAI-1 levels. More studies are needed to establish the clinical relevance of these findings. TRIAL REGISTRATION: EU Clinical Trials Register 2012-004950-27.

Profibrinolytic effect of the epigenetic modifier valproic acid in man.

AIMS: The aim of the study was to test if pharmacological intervention by valproic acid (VPA) treatment can modulate the fibrinolytic system in man, by means of increased acute release capacity of tissue plasminogen activator (t-PA) as well as an altered t-PA/Plasminogen activator inhibitor -1 (PAI-1) balance. Recent data from in vitro research demonstrate that the fibrinolytic system is epigenetically regulated mainly by histone deacetylase (HDAC) inhibitors. HDAC inhibitors, including VPA markedly upregulate t-PA gene expression in vitro. METHODS AND RESULTS: The trial had a cross-over design where healthy men (n = 10), were treated with VPA (Ergenyl Retard) 500 mg depot tablets twice daily for 2 weeks. Capacity for stimulated t-PA release was assessed in the perfused-forearm model using intra-brachial Substance P infusion and venous occlusion plethysmography. Each subject was investigated twice, untreated and after VPA treatment, with 5 weeks wash-out in-between. VPA treatment resulted in considerably decreased levels of circulating PAI-1 antigen from 22.2 (4.6) to 10.8 (2.1) ng/ml (p<0.05). It slightly decreased the levels of circulating venous t-PA antigen (p<0.05), and the t-PA:PAI-1 antigen ratio increased (p<0.01). Substance P infusion resulted in an increase in forearm blood flow (FBF) on both occasions (p<0.0001 for both). The acute t-PA release in response to Substance P was not affected by VPA (p = ns). CONCLUSION: Valproic acid treatment lowers plasma PAI-1 antigen levels and changes the fibrinolytic balance measured as t-PA/PAI-1 ratio in a profibrinolytic direction. This may in part explain the reduction in incidence of myocardial infarctions by VPA treatment observed in recent pharmacoepidemiological studies. TRIAL REGISTRATION: The EU Clinical Trials Register 2009-011723-31.

Acute vascular effects of atorvastatin in hypertensive men: a pilot study.

OBJECTIVES: Statins have multiple pleiotropic effects that are independent of their cholesterol-lowering properties including rapid improvement of endothelial function in vitro. Hypertension is characterized by endothelial dysfunction and we hypothesized that a single-dose of atorvastatin may have an acute effect on vascular function. DESIGN: Endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation were assessed with venous occlusion plethysmography during intra-arterial infusion of acetylcholine (ACH) and sodium nitroprusside (SNP), respectively, in 13 hypertensive men after wash-out from antihypertensive medication. Vasoconstrictive responses were evaluated in response to angiotensin II (Ang II) infusion. The protocol was repeated 1 h after 80 mg oral atorvastatin (ATV; Lipitor(®)). RESULTS: ATV treatment significantly increased baseline forearm blood flow from 3.38 (0.27) to 4.31 (0.35) ml/min/100 ml tissue (p < 0.05). ATV did not affect ACH-induced EDV. Forearm vascular resistance in response to SNP was significantly lowered by ATV (p < 0.05). Vasoconstriction in response to Ang II was significantly inhibited by ATV treatment (p = 0.005). CONCLUSIONS: The observed acute statin effects in hypertension appear to be endothelium-independent and related to vascular smooth muscle cell function. These actions may in part contribute to the beneficial pleiotropic effects of statin therapy even in the acute in vivo setting.

The impaired fibrinolytic capacity in hypertension is unaffected by acute blood pressure lowering.

The endogenous fibrinolytic system and the ability of the endothelium to release tissue-plasminogen activator (t-PA) play a pivotal role to protect humans from atherothrombotic events. We have recently reported that the decreased capacity for t-PA release in hypertension is restored with chronic blood pressure lowering. Thus, we explored if acute blood pressure lowering has the same effect. The capacity for acute t-PA release was investigated in the perfused-forearm model during stimulation by intra-arterial substance P 8 pmol/min in hypertensive subjects. The procedure was then repeated during acute blood pressure lowering (n = 9) induced by sodium nitroprusside (SNP) infusion or during placebo infusion (n = 3). SNP lowered mean arterial pressure from 108.6 (2.6) to 83.0 (2.6) (mean and SEM) mmHg (P < 0.001). Substance P induced significant increase in t-PA release during both high- and low-pressure conditions (P < 0.01, ANOVA). Peak t-PA release rate was 199 (77) and 167 (41) (mean and SEM) ng/min/l tissue, and accumulated t-PA release was 2,395 (750) and 2,394 (473) ng, during high- and low-pressure conditions, respectively. t-PA release and hemodynamic responses were almost identical during high- and low-pressure conditions (P = ns, for all). Acute blood pressure lowering does not restore stimulated t-PA release from the endothelium in hypertensive subjects. These findings are in contrast to previously described effects of chronic blood pressure treatment. Although data need to be confirmed in a larger study, they suggest that high blood pressure decreases the cellular t-PA pool rather than interferes with release mechanisms of the protein.