Predictive value of the PRAETORIAN score for defibrillation test success in patients with subcutaneous ICD: A subanalysis of the PRAETORIAN-DFT trial.

BACKGROUND: The PRAETORIAN score estimates the risk of failure of subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy by using generator and lead positioning on bidirectional chest radiographs. The PRospective randomized compArative trial of subcutanEous implanTable cardiOverter-defibrillatoR ImplANtation with and without DeFibrillation Testing (PRAETORIAN-DFT) investigates whether PRAETORIAN score calculation is noninferior to defibrillation testing (DFT) with regard to first shock efficacy in spontaneous events. OBJECTIVE: This prespecified subanalysis assessed the predictive value of the PRAETORIAN score for defibrillation success in induced ventricular arrhythmias. METHODS: This multicenter investigator-initiated trial randomized 965 patients between DFT and PRAETORIAN score calculation after de novo S-ICD implantation. Successful DFT was defined as conversion of induced ventricular arrhythmia in <5 seconds from shock delivery within 2 attempts. Bidirectional chest radiographs were obtained after implantation. The predictive value of the PRAETORIAN score for DFT success was calculated for patients in the DFT arm. RESULTS: In total, 482 patients were randomized to undergo DFT. Of these patients, 457 (95%) underwent DFT according to protocol, of whom 445 (97%) had successful DFT and 12 (3%) had failed DFT. A PRAETORIAN score of ≥90 had a positive predictive value of 25% for failed DFT, and a PRAETORIAN score of <90 had a negative predictive value of 99% for successful DFT. A PRAETORIAN score of ≥90 was the strongest independent predictor for failed DFT (odds ratio 33.77; confidence interval 6.13-279.95; P < .001). CONCLUSION: A PRAETORIAN score of <90 serves as a reliable indicator for DFT success in patients with S-ICD, and a PRAETORIAN score of ≥90 is a strong predictor for DFT failure.

Association Between Self-Rated Medication Adherence and Adverse Cardiovascular Outcomes in Patients With Hypertension.

Background Medication nonadherence contributes to poor health outcomes but remains challenging to identify. This study assessed the association between self-rated adherence and systolic blood pressure, low-density lipoprotein cholesterol levels, cardiovascular events, and all-cause mortality in SPRINT (Systolic Blood Pressure Intervention Trial). Methods and Results A total of 9361 patients randomized to 2 systolic blood pressure target groups, <120 mm Hg (intensive) and <140 mm Hg (standard), self-rated their medication adherence at each visit by marking a scale, ranging from 0% to 100%. Lower and high adherence were defined as scores ≤80% and >80%, respectively. Linear mixed effect regression models and Cox proportional hazard models were used to evaluate the association between self-rated adherence and systolic blood pressure and low-density lipoprotein cholesterol and cardiovascular events and all-cause mortality, respectively. A total of 9278 participants (mean age 68±9.4 years, 35.6% female) had repeated self-rated adherence measurements available, with a mean of 15±4 measurements per participant over 3.8 years follow-up. Of these, 2694 participants (29.0%) had ≥1 adherence measurements ≤80%. Compared with high-adherent patients, patients with lower adherence had significantly higher estimated on-treatment systolic blood pressure at 2-year follow-up: 128.7 (95% CI, 127.6-129.9) versus 120.0 (95% CI, 119.7-120.2) mm Hg in the intensive arm; and 139.8 (95% CI 138.4-141.1) versus 135.0 (95% CI 134.7-135.2) in the standard arm. Moreover, lower adherence was associated with an estimated 11 mg/dL higher low-density lipoprotein cholesterol level, more cardiovascular events (hazard ratio [HR], 1.69 [95% CI, 1.20-2.39]), and higher all-cause mortality (HR, 1.63 [95% CI, 1.16-2.31]). Conclusions Self-rated adherence allows identification of lower medication adherence and correlates with blood pressure control, low-density lipoprotein cholesterol levels, and adverse outcomes.

Voltage gradients in transvenous and subcutaneous defibrillation and their risk of myocardial damage.

INTRODUCTION: Transvenous implantable cardioverter-defibrillator (ICD) shocks have been associated with cardiac biomarker elevations and are thought in some cases to contribute to adverse clinical outcomes and mortality, possibly from myocardium exposed to excessive shock voltage gradients. Currently, there are only limited data for comparison with subcutaneous ICDs. We sought to compare ventricular myocardium voltage gradients resulting from transvenous (TV) and subcutaneous defibrillator (S-ICD) shocks to assess their risk of myocardial damage. METHODS: A finite element model was derived from thoracic magnetic resonance imaging (MRI). Voltage gradients were modeled for an S-ICD with a left-sided parasternal coil and a left-sided TV-ICD with a mid-cavity, a septal right ventricle (RV) coil, or a dual coil lead (TV mid, TV septal, TV septal + superior vena cava [SVC]). High gradients were defined as > 100 V/cm. RESULTS: The volumes of ventricular myocardium with high gradients > 100 V/cm were 0.02, 2.4, 7.7, and 0 cc for TV mid, TV septal, TV septal + SVC, and S-ICD, respectively. CONCLUSION: Our models suggest that S-ICD shocks produce more uniform gradients in the myocardium, with less exposure to potentially damaging electrical fields, compared to TV-ICDs. Dual coil TV leads yield higher gradients, as does closer proximity of the shock coil to the myocardium.

Device-related complications in subcutaneous versus transvenous ICD: a secondary analysis of the PRAETORIAN trial.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is developed to overcome lead-related complications and systemic infections, inherent to transvenous ICD (TV-ICD) therapy. The PRAETORIAN trial demonstrated that the S-ICD is non-inferior to the TV-ICD with regard to the combined primary endpoint of inappropriate shocks and complications. This prespecified secondary analysis evaluates all complications in the PRAETORIAN trial. METHODS AND RESULTS: The PRAETORIAN trial is an international, multicentre, randomized trial in which 849 patients with an indication for ICD therapy were randomized to receive an S- ICD (N = 426) or TV-ICD (N = 423) and followed for a median of 49 months. Endpoints were device-related complications, lead-related complications, systemic infections, and the need for invasive interventions. Thirty-six device-related complications occurred in 31 patients in the S-ICD group of which bleedings were the most frequent. In the TV-ICD group, 49 complications occurred in 44 patients of which lead dysfunction was most frequent (HR: 0.69; P = 0.11). In both groups, half of all complications were within 30 days after implantation. Lead-related complications and systemic infections occurred significantly less in the S-ICD group compared with the TV-ICD group (P < 0.001, P = 0.03, respectively). Significantly more complications required invasive interventions in the TV-ICD group compared with the S-ICD group (8.3% vs. 4.3%, HR: 0.59; P = 0.047). CONCLUSION: This secondary analysis shows that lead-related complications and systemic infections are more prevalent in the TV-ICD group compared with the S-ICD group. In addition, complications in the TV-ICD group were more severe as they required significantly more invasive interventions. This data contributes to shared decision-making in clinical practice.

Efficacy and Safety of Appropriate Shocks and Antitachycardia Pacing in Transvenous and Subcutaneous Implantable Defibrillators: Analysis of All Appropriate Therapy in the PRAETORIAN Trial.

BACKGROUND: The PRAETORIAN trial (A Prospective, Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy) showed noninferiority of subcutaneous implantable cardioverter defibrillator (S-ICD) compared with transvenous implantable cardioverter defibrillator (TV-ICD) with regard to inappropriate shocks and complications. In contrast to TV-ICD, S-ICD cannot provide antitachycardia pacing for monomorphic ventricular tachycardia. This prespecified secondary analysis evaluates appropriate therapy and whether antitachycardia pacing reduces the number of appropriate shocks. METHODS: The PRAETORIAN trial was an international, investigator-initiated randomized trial that included patients with an indication for implantable cardioverter defibrillator (ICD) therapy. Patients with previous ventricular tachycardia <170 bpm or refractory recurrent monomorphic ventricular tachycardia were excluded. In 39 centers, 849 patients were randomized to receive an S-ICD (n=426) or TV-ICD (n=423) and were followed for a median of 49.1 months. ICD programming was mandated by protocol. Appropriate ICD therapy was defined as therapy for ventricular arrhythmias. Arrhythmias were classified as discrete episodes and storm episodes (≥3 episodes within 24 hours). Analyses were performed in the modified intention-to-treat population. RESULTS: In the S-ICD group, 86 of 426 patients received appropriate therapy, versus 78 of 423 patients in the TV-ICD group, during a median follow-up of 52 months (48-month Kaplan-Meier estimates 19.4% and 17.5%; P=0.45). In the S-ICD group, 83 patients received at least 1 shock, versus 57 patients in the TV-ICD group (48-month Kaplan-Meier estimates 19.2% and 11.5%; P=0.02). Patients in the S-ICD group had a total of 254 shocks, compared with 228 shocks in the TV-ICD group (P=0.68). First shock efficacy was 93.8% in the S-ICD group and 91.6% in the TV-ICD group (P=0.40). The first antitachycardia pacing attempt successfully terminated 46% of all monomorphic ventricular tachycardias, but accelerated the arrhythmia in 9.4%. Ten patients with S-ICD experienced 13 electrical storms, versus 18 patients with TV-ICD with 19 electrical storms. Patients with appropriate therapy had an almost 2-fold increased relative risk of electrical storms in the TV-ICD group compared with the S-ICD group (P=0.05). CONCLUSIONS: In this trial, no difference was observed in shock efficacy of S-ICD compared with TV-ICD. Although patients in the S-ICD group were more likely to receive an ICD shock, the total number of appropriate shocks was not different between the 2 groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022.

Complications related to elective generator replacement of the subcutaneous implantable defibrillator.

AIMS: To guarantee uninterrupted function of the subcutaneous implantable cardioverter-defibrillator (S-ICD), the pulse generator needs to be surgically replaced before the battery is depleted. The risks related to this replacement substantially impact long-term outcome for S-ICD recipients, as the majority will undergo one or several of these procedures in their lifetime. We aim to describe the procedural characteristics of the replacement procedure and to provide an insight in the complications associated with these replacements. METHODS AND RESULTS: In this retrospective analysis, data from replacement procedures and follow-up visits were collected from all patients who underwent elective S-ICD generator replacement in our tertiary centre from June 2014 until November 2019. Original device position was assessed using the PRAETORIAN score. Complications were defined as those requiring surgical intervention, systemic antibiotic treatment, or device extraction. Seventy-two patients were included, with a median follow-up of 1.9 years (IQR 0.6-3.3 years) after replacement. Battery depletion occurred after 5.9 ± 0.7 years. The pulse generator was repositioned in patients with a PRAETORIAN score ≥90 to minimize the defibrillation threshold. Although there was an increase in impedance compared to the implant procedure, first shock conversion rate during defibrillation testing was 91.4% with a success rate of 100% after multiple attempts. Two patients developed a complication after, respectively, 9 and 21 months, resulting in a complication rate of 1.4% per year. CONCLUSION: With a median follow-up of 1.9 years, this study shows a low complication rate after S-ICD replacement, with a first shock conversion rate of 91.4%.

Subcutaneous or Transvenous Defibrillator Therapy.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) was designed to avoid complications related to the transvenous ICD lead by using an entirely extrathoracic placement. Evidence comparing these systems has been based primarily on observational studies. METHODS: We conducted a noninferiority trial in which patients with an indication for an ICD but no indication for pacing were assigned to receive a subcutaneous ICD or transvenous ICD. The primary end point was the composite of device-related complications and inappropriate shocks; the noninferiority margin for the upper boundary of the 95% confidence interval for the hazard ratio (subcutaneous ICD vs. transvenous ICD) was 1.45. A superiority analysis was prespecified if noninferiority was established. Secondary end points included death and appropriate shocks. RESULTS: A total of 849 patients (426 in the subcutaneous ICD group and 423 in the transvenous ICD group) were included in the analyses. At a median follow-up of 49.1 months, a primary end-point event occurred in 68 patients in the subcutaneous ICD group and in 68 patients in the transvenous ICD group (48-month Kaplan-Meier estimated cumulative incidence, 15.1% and 15.7%, respectively; hazard ratio, 0.99; 95% confidence interval [CI], 0.71 to 1.39; P = 0.01 for noninferiority; P = 0.95 for superiority). Device-related complications occurred in 31 patients in the subcutaneous ICD group and in 44 in the transvenous ICD group (hazard ratio, 0.69; 95% CI, 0.44 to 1.09); inappropriate shocks occurred in 41 and 29 patients, respectively (hazard ratio, 1.43; 95% CI, 0.89 to 2.30). Death occurred in 83 patients in the subcutaneous ICD group and in 68 in the transvenous ICD group (hazard ratio, 1.23; 95% CI, 0.89 to 1.70); appropriate shocks occurred in 83 and 57 patients, respectively (hazard ratio, 1.52; 95% CI, 1.08 to 2.12). CONCLUSIONS: In patients with an indication for an ICD but no indication for pacing, the subcutaneous ICD was noninferior to the transvenous ICD with respect to device-related complications and inappropriate shocks. (Funded by Boston Scientific; PRAETORIAN ClinicalTrials.gov number, NCT01296022.).

Long-term follow-up of the two-incision implantation technique for the subcutaneous implantable cardioverter-defibrillator.

INTRODUCTION: The two-incision implantation technique of the subcutaneous implantable cardioverter-defibrillator (S-ICD) was introduced as an alternative to the standard three-incision approach by omitting the superior parasternal incision. Thereby, complications may be prevented. Short-term follow-up demonstrated the safety and efficacy of the two-incision technique. However, long-term results are lacking. METHODS: This retrospective study included patients implanted between February 2009 and June 2020. Patients were divided into a group of patients who were implanted with the standard three-incision technique and a group who were implanted with the two-incision technique. Outcomes were defibrillation impedance and efficacy and complications requiring intervention. RESULTS: A total of 268 patients were included (age 42.4 ± 16.6 years, 35.4% female, BMI 25.1 ± 4.5 kg/m2 ). Thirty-one patients underwent S-ICD implantation with the three-incision technique and 237 patients with the two-incision technique. First shock efficacy during defibrillation testing was 93% in the three-incision group versus 94% in the two-incision group (P = .69), and shock impedance was 85 versus 68 ohms (P = .04). First shock success was 75% versus 76% for spontaneous episodes (P = 1.00). Complication-free survival at 5-year follow-up in the three-incision group was estimated at 0.96 (95% CI 0.90-1.00) versus 0.98 (95% CI 0.96-1.00) in the two-incision group (P = .20) and for inappropriate shocks at 5-year 0.77 (95% CI 0.63-0.94) versus 0.83 (95% CI 0.77-0.89, P = .30), respectively. CONCLUSION: Five-year follow-up in this S-ICD cohort showed similar complication rates and effectiveness of two-incision technique compared to the three-incision technique. This technique offers physicians a less invasive and more simplified implantation procedure for the S-ICD, with a better cosmetic result.

Initial Estimated Glomerular Filtration Rate Decline and Long-Term Renal Function During Intensive Antihypertensive Therapy: A Post Hoc Analysis of the SPRINT and ACCORD-BP Randomized Controlled Trials.

Lowering blood pressure (BP) can lead to an initial decline in estimated glomerular filtration rate (eGFR). However, there is debate how much eGFR decline is acceptable. We performed a post hoc analysis of ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure) and SPRINT (Systolic Blood Pressure Intervention Trial), which randomized patients to intensive or standard systolic BP-targets. We determined the relation between initial decline in mean arterial pressure and eGFR. Subsequently, we stratified patients to BP-target and initial eGFR decrease and assessed the relation with annual eGFR decline after 1 year. A total of 13 266 patients with 41 126 eGFR measurements were analyzed. Up to 10 mm Hg of BP-lowering, eGFR did not change. Hereafter, there was a linear decrease of 3.4% eGFR (95% CI, 2.9%-3.9%) per 10 mm Hg mean arterial pressure decrease. The observed eGFR decline based on 95% of the subjects varied from 26% after 0 mm Hg to 46% with a 40 mm Hg mean arterial pressure decrease. There was no difference in eGFR slope (P=0.37) according to initial eGFR decline and BP-target, with a decrease of 1.24 (95% CI, 1.09-1.39), 1.20 (95% CI, 0.97-1.43), and 1.14 (95% CI, 0.77-1.50) in the 5%, 5% to 20%, and >20% stratum during intensive and 0.95 (95% CI, 0.81-1.09), 1.23 (95% CI, 0.97-1.49), and 1.17 (95% CI, 0.65-1.69) mL/minute per 1.73 m2 per year during standard treatment. In patients at high cardiovascular risk with and without diabetes mellitus, we found no association between initial eGFR and annual eGFR decline during BP-lowering treatment. Our results support that an eGFR decrease up to 20% after BP lowering can be accepted and suggest that the limit can be extended up to 46% depending on the achieved BP reduction. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000620, NCT01206062.

A morphology based deep learning model for atrial fibrillation detection using single cycle electrocardiographic samples.

BACKGROUND: Deep learning (DL) has shown promising results in improving atrial fibrillation (AF) detection algorithms. However, these models are often criticized because of their "black box" nature. AIM: To develop a morphology based DL model to discriminate AF from sinus rhythm (SR), and to visualize which parts of the ECG are used by the model to derive to the right classification. METHODS: We pre-processed raw data of 1469 ECGs in AF or SR, of patients with a history AF. Input data was generated by normalizing all single cycles (SC) of one ECG lead to SC-ECG samples by 1) centralizing the R wave or 2) scaling from R-to- R wave. Different DL models were trained by splitting the data in a training, validation and test set. By using a DL based heat mapping technique we visualized those areas of the ECG used by the classifier to come to the correct classification. RESULTS: The DL model with the best performance was a feedforward neural network trained by SC-ECG samples on a R-to-R wave basis of lead II, resulting in an accuracy of 0.96 and F1-score of 0.94. The onset of the QRS complex proved to be the most relevant area for the model to discriminate AF from SR. CONCLUSION: The morphology based DL model developed in this study was able to discriminate AF from SR with a very high accuracy. DL model visualization may help clinicians gain insights into which (unrecognized) ECG features are most sensitive to discriminate AF from SR.

Net Clinical Benefit of Left Atrial Appendage Closure Versus Warfarin in Patients With Atrial Fibrillation: A Pooled Analysis of the Randomized PROTECT-AF and PREVAIL Studies.

Background The PROTECT-AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) and PREVAIL (Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trials demonstrated noninferiority of left atrial appendage closure (LAAC) to warfarin for the composite end point of stroke, systemic embolism, or cardiovascular death. This study aims to quantify the net clinical benefit (NCB) of LAAC versus warfarin, accounting for differences in clinical impact of different event types. Methods and Results We performed a post hoc analysis of the PROTECT-AF and PREVAIL trials, which randomized atrial fibrillation patients to LAAC or warfarin in a 2:1 fashion. The trials enrolled patients in the United States and Europe between 2005 and 2012 with paroxysmal, persistent, or permanent atrial fibrillation and CHADS2 risk scores ≥1. Relative to an index weight for death (1.0), events were assigned weights based on their disabling effect: (1) stroke event weights were based on modified Rankin scores in the base case analyses, and (2) major bleed (0.05) and pericardial effusion (0.05). NCB was calculated as the sum of weight-adjusted events per 100 patient-years. Among 1114 randomized subjects, the NCB of LAAC was 1.42% per year (95% CI 0.01-2.82, P=0.04) and a relative risk of 0.74 (95% CI 0.56-1.00). NCB point estimates favored warfarin early in follow-up, but trended in favor of LAAC after 1 to 2 years. The benefit of LAAC was preserved across subgroups, with particular benefit observed in the subgroup of prior stroke and without diabetes mellitus. Conclusions This analysis demonstrates long-term NCB of LAAC with Watchman over warfarin therapy, as the upfront risk of periprocedural events is counterbalanced over time by reduced bleeding events and mortality. Clinical Trial Registration UR: http://www.clinicaltrials.gov. Unique identifiers: NCT01182441 and NCT00129545.

Rationale and design of the PRAETORIAN-DFT trial: A prospective randomized CompArative trial of SubcutanEous ImplanTable CardiOverter-DefibrillatoR ImplANtation with and without DeFibrillation testing.

In transvenous implantable cardioverter-defibrillator (TV-ICD) implants, routine defibrillation testing (DFT) does not improve shock efficacy or reduce arrhythmic death but patients are exposed to the risk of complications related to DFT. The conversion rate of DFT in subcutaneous ICD (S-ICD) is high and first shock efficacy is similar to TV-ICD efficacy rates. STUDY DESIGN: The PRAETORIAN-DFT trial is an investigator-initiated, randomized, controlled, multicenter, prospective two-arm trial designed to demonstrate non-inferiority of omitting DFT in patients undergoing S-ICD implantation in which the S-ICD system components are optimally positioned. Positioning of the S-ICD will be assessed with the PRAETORIAN score. The PRAETORIAN score is developed to systematically evaluate implant position of the S-ICD system components which determine the defibrillation threshold on post-operative chest X-ray. A total of 965 patients, scheduled to undergo a de novo S-ICD implantation without contra-indications for either DFT strategy, will be randomized to either standard of care S-ICD implantation with DFT, or S-ICD implantation without DFT but with evaluation of the implant position using the PRAETORIAN score. The study is powered to claim non-inferiority of S-ICD implantation without DFT in de novo S-ICD patients in respect to the primary endpoint of first shock efficacy in spontaneous arrhythmia episodes. Patients with a high PRAETORIAN score (≥90) in the interventional arm of this study will undergo DFT according to the same DFT protocol as in the control arm. CONCLUSION: The PRAETORIAN-DFT trial is a randomized trial that aims to gain scientific evidence to safely omit a routine DFT after S-ICD implantation in patients with correct device positioning.

A novel tool to evaluate the implant position and predict defibrillation success of the subcutaneous implantable cardioverter-defibrillator: The PRAETORIAN score.

BACKGROUND: Suboptimal positioning of the subcutaneous implantable cardioverter-defibrillator (S-ICD) increases the defibrillation threshold and risk of conversion failure. OBJECTIVE: Our objective is to develop a tool to evaluate the implant position and predict defibrillation success of the S-ICD: the PRAETORIAN score. METHODS: The PRAETORIAN score is based on clinical and computer modeling knowledge of determinants affecting the defibrillation threshold: subcoil fat, subgenerator fat, and anterior positioning of the S-ICD generator. The score evaluates these determinants on the postoperative anterior-posterior and lateral chest radiographs and has 3 categories: 30-<90 points representing a low risk, 90-<150 points representing an intermediate risk, and ≥150 points representing a high risk of conversion failure. The score was developed using 2 separate S-ICD data sets for derivation and validation. The performance metrics are the positive and negative predictive values. RESULTS: The development data set consisted of 181 patients with S-ICD, and the validation cohort consisted of 321 patients from the S-ICD Investigational Device Exemption trial. The distribution of scores was 93%-98% low risk (<90 points), 2%-5% intermediate risk (90-<150 points), and 1% high risk (≥150 points). The positive predictive value for an intermediate or high PRAETORIAN score for a failed conversion test was 51%, while a low PRAETORIAN score predicted a successful conversion in 99.8% of patients. CONCLUSION: The PRAETORIAN score allows the identification of patients with high defibrillation thresholds by using the routine chest radiograph and provides feedback to implanters on S-ICD positioning. The PRAETORIAN-DFT trial will prospectively validate the score by randomizing to standard conversion testing vs using the score without conversion testing.

Creatinine Rise During Blood Pressure Therapy and the Risk of Adverse Clinical Outcomes in Patients With Type 2 Diabetes Mellitus.

Lowering blood pressure may affect renal function. Current guidelines state that reducing antihypertensive therapy should be considered in patients with a >30% serum creatinine increase after initiation of antihypertensive therapy. We examined the association between a serum creatinine increase and adverse clinical outcomes in the ACCORD-BP trial (Action to Control Cardiovascular Risk in Diabetes Blood Pressure), were patients with type 2 diabetes mellitus were randomized to intensive (target systolic blood pressure <120 mm Hg) and standard antihypertensive (<140 mm Hg) treatment. The primary outcome was a combined end point consisting of all-cause mortality, major cardiovascular events, and renal failure. Patients were stratified into 3 groups according to serum creatinine increase between baseline and 4 months (<10%, 10%-30%, >30%). A total of 4733 patients, aged 62.2 years, 52% men with a mean estimated glomerular filtration rate 81.5 mL/min per 1.73 m2 were included. Follow-up was available for 4446 patients, 2231 were randomized to intensive and 2215 to standard therapy. Kaplan-Meier analysis showed no association between a serum creatinine increase and the composite end point in the intensive ( P=0.20) and the standard treatment group ( P=0.17). After adjusting for possible confounders, a >30% serum creatinine increase was associated with a higher risk of clinical adverse outcomes in both treatment groups, but to a similar extent. These data suggest that a >30% serum creatinine increase that coincides with lower blood pressure values should not directly lead to a reduction in antihypertensive medication in patients with type 2 diabetes mellitus. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000620.

[Limits to the treatment of hypertension]. / Grenzen aan de behandeling van hypertensie.

According to the 2011 Dutch guideline on Cardiovascular risk management 1 in 5 hypertensive patients are eligible for blood pressure lowering treatment. The Dutch guideline recommends striving for a systolic blood pressure (SBP) of < 140 mmHg in adult patients who have no cardiovascular disease or diabetes mellitus, while the recent American guideline now recommends an SBP target value of < 130 mmHg for all adult patients. An important reason for using a stricter SBP target value are the results of randomised studies and meta-analyses that looked at the effect of intensive antihypertensive therapy on the risk of mortality and cardiovascular disease. Based on the literature, there appears to be sufficient evidence that intensive antihypertensive therapy (SBP target value of < 130 mmHg) is useful in patients with cardiovascular disease and in patients with high cardiovascular risk. Currently, there is insufficient evidence that intensive antihypertensive therapy is useful in patients who have diabetes mellitus or who are over 80 years old.

Clinical parameters to optimize patient selection for subcutaneous and transvenous implantable defibrillator therapy.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) lacks the antitachycardia pacing (ATP) capability of tranvenous ICDs (TV-ICD). S-ICD patient selection can be challenging as some patients may benefit from ATP. We aim to identify clinical predictors of ATP benefit, in order to improve patient selection for S-ICD or TV-ICD therapy. METHODS: De novo single- and dual-chamber TV-ICD patients implanted between March 2011 and December 2015 were included. Ventricular arrhythmias terminated by ATP and not followed by a shock were considered successful ATP therapy. Cox proportional hazard analysis was performed to assess the adjusted effect of multiple predictors for appropriate ATP and shock therapy. RESULTS: Note that 431 patients were included with a median follow-up of 26 months. Ninety-nine patients (23%) received appropriate ATP therapy, which terminated the arrhythmia in 67%. A history of nonsustained ventricular tachycardia (NSVT) or monomorphic VT (MVT) was the only predictor of appropriate ATP therapy in the multivariable model (hazard ratio [HR] 2.73, P < 0.001). Sixty-five of 221 patients with a history of NS (VT) received appropriate ATP (29%) versus 24 patients (11%) without a history NS (VT) (P < 0.001). A secondary prevention indication was the only predictor in the multivariate model for appropriate shock therapy (HR 1.82, P  =  0.05). CONCLUSION: A history of NSVT or MVT is a significant predictor for appropriate and successful ATP therapy. One in three patients with NSVT or MVT received appropriate ATP versus one in 10 patients without a history of NSVT or MVT over a 2-year period of follow-up.

Prospective blinded evaluation of a novel sensing methodology designed to reduce inappropriate shocks by the subcutaneous implantable cardioverter-defibrillator.

BACKGROUND: Most inappropriate shocks from the subcutaneous implantable cardioverter-defibrillator (S-ICD) are caused by cardiac oversensing. A novel sensing methodology, SMART Pass (SP; Boston Scientific Corporation, Natick, MA), aims to reduce cardiac oversensing. OBJECTIVE: The purpose of this study was to evaluate the effect of SP on shocks in ambulatory patients with S-ICD. METHODS: Patients implanted in 2015-2016 and enrolled in a remote patient monitoring system were included and followed for 1 year. Shocks were adjudicated by 3 independent blinded reviewers as appropriate or inappropriate. Shock incidence was calculated for patients with SP programmed enabled or disabled at implantation, censoring patients when SP programming changed or at the last transmission. The SP setting (enabled vs disabled) was modeled as a time-dependent Cox regression variable. RESULTS: The cohort consisted of 1984 patients, and a total of 880 shocks were adjudicated. At implantation, SP was enabled in 655 patients (33%) and disabled in 1329 patients (67%). SP reduced the risk for the first inappropriate shock by 50% (P < .001) and the risk for all inappropriate shocks by 68% (P < .001) in multivariate analysis adjusted for age and device programming. The incidence of inappropriate shocks was 4.3% in the SP enabled arm vs 9.7% in the SP disabled arm. The incidence of appropriate shocks was similar (5.2% vs 6.6%; P = .18) along with the time to treat the first appropriate shock (17.4 seconds vs 16.7 seconds; P = .92) for SP enabled vs disabled, respectively. CONCLUSION: This prospective blinded evaluation of the SP filter demonstrates that enabling the SP filter results in a significant reduction of inappropriate shocks by the S-ICD without a negative effect on appropriate shocks.