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Background: Thromboembolic events, particularly strokes, remain a major complication of transcatheter aortic valve replacement (TAVR). Embolic protection devices have failed to show significant clinical benefit in large randomized clinical trials. Aortic wall thrombus (AWT) is often observed on multidetector computed tomography during TAVR work-up, but its prognostic significance is uncertain., Objectives: This study sought to evaluate the association between the presence of AWT and the incidence of thromboembolic outcomes in patients undergoing transfemoral (TF) TAVR for severe aortic stenosis., Methods: This was a prospective cohort study of consecutive patients who underwent TF TAVR for severe aortic stenosis between January 2011 and April 2022. A dedicated scale (range: 0-10) was qualitatively used to assess AWT. The primary outcome was a composite of procedural thromboembolic events defined as ischemic stroke, blue toe syndrome, bowel ischemia, or other solid organ infarction. The secondary endpoints were ischemic strokes and procedural death., Results: Of the 641 patients included, severe AWT (score ≥8) was identified in 73 (11.4%). The presence of severe AWT was strongly associated with an increase in the primary outcome (OR: 8.48; 95% CI: 3.36-21.40; P < 0.001). This relationship persisted following multivariable analysis, which adjusted for comorbidities and procedural characteristics. The presence of severe AWT was also found to be associated with an increased incidence of stroke and procedural death (OR: 5.66; 95% CI: 2.00-15.30; P = 0.002 and OR: 4.66; 95% CI: 1.80-11.30; P = 0.002, respectively)., Conclusions: The presence of severe AWT on preprocedural multidetector computed tomography is strongly associated with thromboembolic complications including stroke and mortality after TF TAVR., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications., Methods: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426., Findings: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups., Interpretation: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension., Funding: ReCor Medical., Competing Interests: Declaration of interests MA has received research grants from the French Ministry of Health, Quantum Genomics, and the European Horizon 2020 programme; has received grant support and non-financial support from ReCor Medical and Idorsia; and has received personal fees from CVRx, AstraZeneca, Alnylam Pharmaceutical, and Poxel Pharma. KS has received grant support and personal fees from ReCor Medical and Medtronic, and has received grant support from Cardiovascular Systems. MSax has received grant support and personal fees from ReCor Medical. PG has received grant support from the University Hospital of Bordeaux. LCR has received personal fees from ReCor Medical. APe has received personal fees from Quantum Genomics and grant support from Ablative Solutions, Quantum Genomics, and ReCor Medical. JB has received grant support from ReCor Medical and Ablative Solutions. MJB has received personal fees from ReCor Medical and Medtronic. JD has received grant support from ReCor Medical, Medtronic, Boston Scientific, Abbott Vascular, Acist Medical, AstraZeneca, Pie Medical, and Pulse Cath, and personal fees from ReCor Medical, Medtronic, Acist Medical, Boston Scientific, Pie Medical, and Pulse Cath. MDL has received personal fees from ReCor Medical, Medtronic, CVRx, Ablative Solutions, Vascular Dynamics, ROX Medical, and Tarilan Laser Technologies, and grants from Medtronic. FM is supported by Deutsche Gesellschaft für Kardiologie and Deutsche Forschungsgemeinschaft (SFB TRR 219); and has received grant support and personal fees from ReCor Medical, Medtronic, Berlin Chemie, Bayer, and Boehringer Ingelheim. RES has received grant support and personal fees from ReCor Medical, Medtronic, and Ablative Solutions. ASPS has received personal fees from ReCor Medical, Medtronic, Boston Scientific, and Philips. MAW has received personal fees from ReCor Medical, Medtronic, Boston Scientific, and Ablative Solutions. APa has received grant support and personal fees from ReCor Medical, Medtronic, and Ablative Solutions. DH reports institutional funding to Stamford Hospital from ReCor Medical. SB has received grant support from Abbott Vascular, the National Heart, Lung, and Blood Institute, and REATA; and personal fees from Abbott Vascular, Biotronik, REATA, Amgen, Pfizer, Boehringer Ingelheim, and Meril. JW has received personal fees from ReCor Medical and Medtronic. NCB is an employee of ReCor Medical and is the author on multiple patents in the field of renal denervation. HR-S is an employee of ReCor Medical. LC is an employee of ReCor Medical. CKM is an employee of North American Science Associates and a contractor for ReCor Medical. AJK reports institutional funding (in addition to research grants, institutional funding includes fees paid for speaking engagements or consulting) to Columbia University or the Cardiovascular Research Foundation (New York, NY, USA) from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, Cardiovascular Systems, CathWorks, Siemens, Philips, and ReCor Medical. AJK also reports travel expenses or meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, Cardiovascular Systems, CathWorks, Siemens, Philips, Chiesi, OpSens, Zoll, Regeneron, and ReCor Medical. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Backgrounds: Data on optimal antiplatelet therapy in patients undergoing stenting of the proximal left anterior descending artery (LAD) are limited., Methods: This is a post-hoc analysis of the GLOBAL LEADERS trial, a prospective, multi-center, randomized controlled trial, comparing the experimental strategy (1-month dual anti-platelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) with the reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) in relation to stenting of the proximal LAD. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction (MI) and key secondary safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at two years., Results: Among 15,845 patients included in the analysis, 3823 (23.9%) patients underwent stenting of the proximal LAD, while 12,022 (75.2%) did not. In the proximal LAD stenting group, there was no significant difference in the risk of the primary endpoint between the two antiplatelet strategies (3.38% vs. 3.93%; hazard ratio [HR]:0.86; 95% CI:0.62-1.20; P interaction  = 0.951). However, the risk of any MI (2.63% vs. 3.88%; HR:0.68; 95% CI:0.47-0.97; P interaction  = 0.015) and any revascularization (7.84% vs. 9.94%; HR:0.78; 95% CI:0.63-0.97; P interaction  = 0.058) was significantly lower in the experimental strategy group, while demonstrating a similar risk of BARC type 3 or 5 bleeding between the two antiplatelet strategies (1.93% vs. 1.99%; HR:0.98; 95% CI:0.62-1.54; P interaction  = 0.981)., Conclusions: The present study showed patients having stenting to the proximal LAD could potentially benefit from the experimental strategy with lower ischaemic events without a trade-off in major bleeding at two years., Competing Interests: Declaration of Competing Interest Dr. Hara reports grant from Japanese Circulation Society and Fukuda Foundation for Medical Technology, outside the submitted work; Dr. de Winter reports unrestricted educational research grant from Astra Zeneca for Acadamic Medical Center, University of Amsterdam, the Netherlands, outside the submitted work; Dr. Hamm reports personal fees from AstraZeneca, outside the submitted work; Dr. Steg reports grants and personal fees from Bayer/Janssen, grants and personal fees from Merck, grants and personal fees from Sanofi, grants and personal fees from Amarin, personal fees from Amgen, personal fees from Bristol Myers Squibb, personal fees from Boehringer-Ingelheim, personal fees from Pfizer, personal fees from Novartis, personal fees from Regeneron, personal fees from Lilly, personal fees from AstraZeneca, grants and personal fees from Servier, outside the submitted work; Dr. Windecker reports research and educational grants to the institution from Abbott, Amgen, BMS, Bayer, Boston Scientific, Biotronik, Cardinal Health, CardioValve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Johnson& Johnson, Medtronic, Querbet, Polares, Sanofi, Terumo, Sinomed, outside the submitted work. He serves as unpaid member of the steering/excecutive group of trials funded by Abbott, Abiomed, Amgen, BMS, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Polares, Sinomed, V-Wave and Xeltis, but has not received personal payments by any pharmaceutical company or device manufacturer. He is also member of the steering/excecutive committee group of several investigated-initiated trials that receive funding by industry without impact on his personal remuneration. Dr. Vranckx reports personal fees from Astra Zeneca, personal fees from The Medicines Company, during the conduct of the study; personal fees from Bayer Health Care, personal fees from Daiichi Sankyo, personal fees from Terumo, personal fees from CLS Bhering, outside the submitted work; Dr. Valgimigli reports grants and personal fees from Abbott, personal fees from Chiesi, personal fees from Bayer, personal fees from Daiichi Sankyo, personal fees from Amgen, grants and personal fees from Terumo, personal fees from Alvimedica, grants from Medicure, grants and personal fees from Astrazeneca, personal fees from Biosensors, personal fees from Idorsia, outside the submitted work; Dr. Serruys reports personal fees from Abbott Laboratories, personal fees from AstraZeneca, personal fees from Biotrinik, personal fees from GLG Research, personal fees from Medtronic, personal fees from Sino Medical Sciences Technology, personal fees from Société Europa Digital Publishing, personal fees from Stentys France, personal fees from Svelte Medical Systems, personal fees from Philips/Volcano, personal fees from Qualimed, personal fees from Xeltis, outside the submitted work; All other authors declare no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The number of TAVI procedures is rapidly increasing owing to the extension of indications. Procedural and long-term success warrant appropriate patient selection and rigorous preparation of the procedure during the pre-TAVI work-up. The aims of this work-up are several: validation of the indication, feasibility and safety of the procedure, selection of the prosthesis and of the route, anticipation of technical challenges. The CT-scan is the cornerstone of this assessment allowing for valve and vascular access appraisal. The geriatric evaluation remains important in the elderly, frail, high-risk patients. The assessment of cardiac and extracardiac comorbidities is systematic and may be incorporated into dedicated risk scores to improve the prediction of post-TAVI outcomes; this should be the basis of the decision-making process by the Heart Team., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Predictors of heart failure (HF) hospitalization after transcatheter aortic valve implantation (TAVI) are not well defined. CAPRI is a score for predicting 1-year post-TAVI cardiovascular and all-cause mortality. The aim of the present study is to assess the prognostic significance of the CAPRI score for HF hospitalization 1 year after TAVI., Methods and Results: CAPRI-HF is an ancillary study of the C4CAPRI trial, analyzing 409 consecutive patients treated by TAVI. The primary outcome was hospitalization for HF during the first year post-intervention. The prognostic value of the CAPRI score was assessed by multivariable analysis adjusted for diabetes, atrial fibrillation, vascular route, pacemaker implantation, post-TAVI aortic regurgitation, transfusion and pulmonary artery systolic pressure. A subanalysis focused on patients with low-gradient aortic stenosis (LGAS). At 1 year, HF hospitalization occurred in 78 (19.9%) patients. Patients with HF were more prone to have diabetes, atrial fibrillation, renal dysfunction, lower mean aortic gradient, higher logistic EuroSCORE and higher CAPRI score (p < .05 for all associations). In the multivariable analysis, CAPRI score was the sole predictor of HF: hazard ratio (HR) for each 0.1 CAPRI score increase was 1.065, 95% confidence interval (CI) 1.021-1.110. This was confirmed when adjusted for EuroSCORE: HR 1.066, 95% CI 1.024-1.110. The predictive power of the CAPRI score increased for LGAS: HR 1.098, 95% CI 1.028-1.172., Conclusions: CAPRI score helps predict HF post-TAVI. Including the score in the decision-making process may help selecting candidates for TAVI and identifying patients who need close monitoring post-procedure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Traditional cancer therapies, such as treatment with anthracyclines and chest radiation, are known to induce cardiovascular complications. Currently, the increase of cancer therapies will involve new mechanisms such as cancer immunotherapies, also called immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors). These treatments have shown long-term remissions in subgroup of cancers, including melanomas, non-small-cell lung cancer, urothelial carcinoma, renal cell carcinoma, squamous cell carcinoma of the head and neck and colorectal cancer. Although these treatments will change the natural course of these cancers, they may sometimes induce cardiovascular complications, which has been reported as about 1 % in the literature. Currently, the physicians must keep in mind one uncommon but severe cardiac complication: auto-immune myocarditis. The clinical presentation may include various symptoms like chest pain, heart failure or rhythm disorders. In this situation, a baseline cardiologic check-up before starting cancer immunotherapy may be very helpful. Cardiac biomarkers (troponin and brain natriuretic peptide) and 12-lead resting electrocardiogram must be promptly performed when myocarditis is suspected. A cardiologist's opinion must be requested in emergency to discuss both a transthoracic echocardiography and the appropriate treatment (stopping immunotherapy, adding immunosuppressive treatment such as corticoids) and the monitoring in an intensive care unit. Cardiac MRI and endomyocardial biopsies may help to approach the final diagnosis. In this situation, other cancer therapies may be discussed., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of this study was to develop a new scoring system based on thoracic aortic calcification (TAC) to predict 1-year cardiovascular and all-cause mortality., Background: A calcified aorta is often associated with poor prognosis after transcatheter aortic valve replacement (TAVR). A risk score encompassing aortic calcification may be valuable in identifying poor TAVR responders., Methods: The C 4 CAPRI (4 Cities for Assessing CAlcification PRognostic Impact) multicenter study included a training cohort (1,425 patients treated using TAVR between 2010 and 2014) and a contemporary test cohort (311 patients treated in 2015). TAC was measured by computed tomography pre-TAVR. CAPRI risk scores were based on the linear predictors of Cox models including TAC in addition to comorbidities and demographic, atherosclerotic disease and cardiac function factors. CAPRI scores were constructed and tested in 2 independent cohorts., Results: Cardiovascular and all-cause mortality at 1 year was 13.0% and 17.9%, respectively, in the training cohort and 8.2% and 11.8% in the test cohort. The inclusion of TAC in the model improved prediction: 1-cm 3 increase in TAC was associated with a 6% increase in cardiovascular mortality and a 4% increase in all-cause mortality. The predicted and observed survival probabilities were highly correlated (slopes >0.9 for both cardiovascular and all-cause mortality). The model's predictive power was fair (AUC 68% [95% confidence interval [CI]: 64% to 72%]) for both cardiovascular and all-cause mortality. The model performed similarly in the training and test cohorts., Conclusions: The CAPRI score, which combines the TAC variable with classical prognostic factors, is predictive of 1-year cardiovascular and all-cause mortality. Its predictive performance was confirmed in an independent contemporary cohort. CAPRI scores are highly relevant to current practice and strengthen the evidence base for decision making in valvular interventions. Its routine use may help prevent futile procedures., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aortic stenosis is a frequent disease in the elderly. Its prevalence is 0.4% with a sharp increase after the age of 65, and its outcome is very poor when the patient becomes symptomatic. The interventional procedure known as TAVI (trans-catheter aortic valve implantation), which was developed in France and carried out for the first time in Rouen by Prof. Alain Cribier and his team in 2002, has proven to be a valid alternative to surgical aortic valve replacement. At first, this technique was shown to be efficient in patients with contra-indications to surgical treatment or deemed to be at high surgical risk. Given the very promising outcomes achieved as a result of close heart team collaboration, appropriate patient selection, simplified procedures and reduced complication rates, transfemoral (TF) TAVI is now preferred in symptomatic intermediate risk patients>75 years old according to the latest ESC guidelines. In 2017, in France, TAVI is currently performed in 50 centers with on-site cardiac surgery. The 2016 TAVI outcomes recorded in the French national TAVI registry (France TAVI) are very encouraging and show that for 7133 patients treated (age 83.4±7 years, logistic Euroscore 14%), 87% of whom via the TF approach, cross-over to surgery was very low (0.5%) with a 3.0% in-hospital mortality rate. The substantial increase in TAVI indications and the improvement of its outcomes may in the near future call for a reconsideration of the number of high volume centers authorized to carry out this technique., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background and Aims: Pulse pressure (PP) is a surrogate of aortic stiffness (AS) easily obtainable. The link between AS and cardio-vascular disease is documented, however, data regarding acute coronary syndrome (ACS) patients are scarce and contradictory. We aimed to assess the prognostic value of PP measured at admission, with regard to major adverse outcomes (all-cause mortality, recurrence of MI, and stroke), during the first year following an acute coronary syndrome (ACS)., Methods: The SPUM-ACS project is a prospective cohort study of patients with ACS conducted in 4 Swiss University hospitals. Patients with no PP at admission or with severe clinical heart failure or cardiogenic shock were excluded. Cox regression analyses were performed to determine associations between PP and outcomes (all-cause mortality, recurrence of myocardial infarction (MI), and stroke). Three multivariate Cox regression models were adjusted for hemodynamic, cardiovascular, and non-cardiovascular confounders, added successively., Results: Of 5635 eligible patients, 5070 met the inclusion criteria. Mean patient age was 63 years (range: 54-72), 79.6% were male, and mean blood pressure and PP were 93.9 ± 15.6 and 54 ± 17 mmHg, respectively. Multivariate analyses confirmed the prognostic significance of PP for each 10-mmHg increase for the composite endpoint, hazard ratio (HR) 1.126 [1.051-1.206], p = 0.001; all-cause mortality, HR1.129 [1.013-1.260], p = 0.029; and recurrence of MI, HR1.206 [1.102-1.320], p < 0.001; but not for stroke, HR1.014[0.853-1.205]., Conclusions: PP measured at admission is a strong, independent prognostic marker predicting mortality and recurrence of MI after ACS. PP should be considered for the management of secondary prevention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: Orthostatic blood pressure decrease or increase has been related to cardiovascular events in hypertensive patients. Large blood pressure changes after orthostatic stress are associated with autonomic and neurohormonal abnormalities; aortic atherosclerosis (ATS) may also play a role., Methods: We investigated the interaction of ATS on the prognostic value of postural blood pressure changes. In a cohort of 958 hypertensive patients with an aortography (mean ± standard deviation age 44 ± 11 years, 61% men, mean blood pressure 182/110 mmHg), blood pressure was measured after 10 min of rest in the supine position. Systolic blood pressure (SBP) was also measured in standing position, 1 min after the supine position. Blood pressure changes were calculated as supine SBP minus standing SBP and analyzed as absolute or arithmetic means. ATS was assessed using an aortography score., Results: After 15 years of follow-up, 280 all-cause and 167 cardiovascular deaths occurred. In a multivariable Cox regression analysis adjusted for major cardiovascular risk factors and stratified according to ATS status, SBP changes were statistically associated with all-cause and cardiovascular mortality only in the presence of ATS: tertile 3 versus 1, 2.99 (1.37-6.49) and 4.08 (1.55-10.72) respectively, tertile 3 versus 2, 2.89 (1.29-6.46) and 4.82 (1.79-12.98), respectively (p for interaction: 0.003 for all-cause and 0.003 for cardiovascular mortality) for absolute changes. The hazard associated with the magnitude of SBP changes was more important than that associated with its direction., Conclusions: The prognostic significance of postural SBP changes is markedly influenced by ATS in hypertensive patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Sudden cardiac death in young athlete is always tragic. Some international guidelines recommend the realization of an electrocardiogram before practicing competitive sports to carry out the risk of sudden cardiac death due to genetic cardiopathy like QT long syndrome. Unfortunately, the diagnosis can be difficult because intensive sport can increase the QT interval over normal recognized values for sedentary people. Using a QT correction formula free of heart rate appears essential., Patients and Methods: Four hundred and forty-six young athletes (aged 10 to 18) had an electrocardiogram. QT intervals were measured and four methods were used to correct the QT interval for heart rate., Results: The Bazett formula performed the worst in terms of rate adjustment success. Hodges and Fridericia formulas are the best both in males and females, independently of age. Female had longer QTc intervals than males., Conclusion: The most widely used Bazett formula should be surrendered whereas Hodges and Fridericia formulas should be preferred, particularly in young athletes., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: The principal objective was to determine the effect of total aortic calcification (TAC) burden on outcomes (cardiac mortality, all-cause mortality, and heart failure (HF)) after transcatheter aortic valve implantation (TAVI). The secondary aim was to assess the contribution of each segment of the aorta to these outcomes., Background: Indications for TAVI are increasing in number. Even after procedural success, however, some patients die soon afterwards, indicating the futility of TAVI in certain cases., Methods: Aortic calcifications were measured on computed tomography in 164 patients treated by TAVI. TAC, ascending aortic calcification (AsAC), descending aorta calcifications, and abdominal aorta calcifications were expressed as tertiles and their prognostic values were assessed in a multivariable cox analysis adjusted for major confounders including EuroSCORE., Results: Median duration of follow-up was 565 (interquartile range: 246 to 1000) days. TAC (tertile3 vs. tertile1) was significantly and strongly associated with cardiac mortality (hazard ratio [HR]: 16.74; 95% confidence interval [CI]: 2.21 to 127.05; p = 0.006) and all-cause mortality (HR: 2.39; 95% CI: 1.18 to 4.84; p = 0.015) but not with HF (HR: 1.84; 95% CI: 0.87 to 3.90; p = 0.110). Each segment was associated with cardiac mortality, while only AsAC (tertile 3 vs. tertile 1) appeared predictive of HF (hazard ratio: 2.29; 95% CI: 1.12 to 4.66; p = 0.023)., Conclusions: TAC is an integrative predictor of cardiac and all-cause mortality after TAVI. It should be included in the assessment of patients before TAVI in order to predict cardiac outcome after valve replacement and avoid futile interventions., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The relationship between blood pressure (BP) and cardiovascular diseases has been extensively documented. However, the benefit of anti-hypertensive drugs differs according to the type of cardiovascular event. Aortic stiffness is tightly intertwined with BP and aorta cross-talk with small arteries. We endeavored to elucidate which BP component and type of vessel remodeling was predictive of the following outcomes: fatal myocardial infarction (MI), fatal stroke, renal -, coronary- or cerebrovascular-related deaths. Large vessel remodeling was estimated by an aortography-based aortic atherosclerosis score (ATS) while small vessel disease was documented by the presence of a hypertensive retinopathy. We included 1031 subjects referred for hypertension workup and assessed outcomes 30 years later. After adjustment for major risk factors, ATS and pulse pressure (PP) were predictive of coronary events while mean BP (MBP) and retinopathy were not. On the contrary, MBP was predictive of cerebrovascular and renal related deaths while ATS and PP were not. Retinopathy was only predictive of cerebrovascular related deaths. Lastly, the aortic atherosclerosis phenotype and increased PP identified patients prone to develop fatal MI whereas the retinopathy phenotype and increased MBP identified patients at higher risk of fatal stroke. These results illustrate the particular feature of the resistive coronary circulation comparatively to the brain and kidneys' low-resistance circulation. Our results advocate for a rational preventive strategy based on the identification of distinct clinical phenotypes. Accordingly, decreasing MBP levels could help preventing stroke in retinopathy phenotypes whereas targeting PP is possibly more efficient in preventing MI in atherosclerotic phenotypes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension., Methods: The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18-75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777., Findings: Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was -15·8 mm Hg (95% CI -19·7 to -11·9) in the renal denervation group and -9·9 mm Hg (-13·6 to -6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of -5·9 mm Hg (-11·3 to -0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups., Interpretation: In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation., Funding: French Ministry of Health., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: We report the first experience of Lyon's university hospital regarding renal denervation to treat patients with resistant essential hypertension., Patients and Methods: Over a one-year period, 17 patients were treated (12 men, 5 women) with renal denervation. Baseline characteristics were as follows: age 56.5±11.5 years, BMI 33±5kg/m(2) and ambulatory blood pressure 157±16/87±13mmHg with 4.2±1.5 anti-hypertensive treatment., Results: We did not observe intra-operative or early complications. After a median follow-up of 3 months and with the same anti-hypertensive treatment, office systolic blood pressure (SBP) and diastolic blood pressure (DBP) decrease respectively of 20±15 (P<0.001) and 10±13mmHg (P=0.014) (n=17). After six months of follow-up, ambulatory blood pressure (ABPM) decrease of 17.5±14.9mmHg (P=0.027) for SBP and of 10.5±9.6mmHg (P=0.029) for DBP (n=6). Among these patients, five of them were controlled (ABPM inferior to 130/80mmHg) and electrical left ventricular hypertrophy indexes decreased: R wave in aVL lead of 4±3mm (P=0.031), Sokolow index of 3±3mm (P=0.205), Cornell voltage criterion of 9±7mm (P=0.027) and Cornell product of 1310±1104 (P=0.027)., Conclusion: Our results are in accordance with data from other centers. On average blood pressure decreases significantly but important inter individual variations are observed. The procedure seems safe., (Copyright © 2014. Published by Elsevier SAS.)

Objectives: Our study aimed at determining the interaction between the prognostic value of diastolic blood pressure (DBP) and aortic atherosclerosis (ATS)., Background: With aging, equal systolic blood pressures (SBPs) become associated with low DBPs; i.e., high pulse pressures (PPs) become associated with a high risk of cardiovascular death. This association is usually ascribed to aortic stiffening with age but the precise impact of low DBP per se is yet uncertain., Methods: 938 hypertensive patients recruited in the seventies had an aortic ATS score at pretreatment aortography. All-cause and cardiovascular deaths were assessed 20 years later. The prognostic values of DBP and SBP were assessed by a multivariate Cox regression model and their interactions with ATS examined., Results: In the presence of ATS, an increase of 10 mmHg in DBP was associated with a protective effect: hazard ratios 0.84 [0.72-0.99] for cardiovascular death and 0.88 [0.78-1.00] for all-cause death. However, in the absence of ATS, DBP had no prognostic value: hazard ratios 1.05 [0.89-1.23] for cardiovascular death and 0.99 [0.88-1.11] for all-cause death (p for interaction: 0.061 and 0.087, respectively). No interaction was found between SBP and ATS (p for interaction > 0.40)., Conclusions: The prognostic values of DBP and aortic atheroma are not superimposable; yet, they are tightly connected: a low DBP is disadvantageous only in the presence of a pathologic aorta. Aortic atherosclerosis may explain, at least partly, in some high risk populations, the J-shape of the already reported DBP-outcome relationship., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Since 2009 in France, every people practicing sport in competition must have a cardiovascular exam with electrocardiogram, to prevent sudden cardiac death. Sometimes, an echocardiography will be necessary. Little is known about athlete's heart in the young, particularly in the French people., Patients and Methods: One hundred and seven French elite adolescent athletes had an electrocardiogram with echocardiography to establish reference values in this population., Results: QTcorrected (QTc) interval calculated by the Hodges formula, is always in the normal values. Interventricular septal thickness is always ≤ 11 mm and left ventricular end diastolic diameter ≤ 55 mm in about 90 % of the athletes. Females have QTc interval longer than males and interventricular septal thickness finer. Diastolic function (18.9 ± 2.6 cm/s for e', E/e' ratio at 5.3 ± 0.8) is "supernormal" and correlate with age and cardiac frequency. Right ventricular systolic function is always good., Conclusion: Adolescent athlete's heart is normal. If QTc interval is not normal, be afraid of a QT long syndrome. Furthermore, when interventricular septal thickness is > 11 mm or left ventricular end diastolic diameter > 55 mm, myocardiopathy will have to be ruled out., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objective: Genesis of sleep apnoea syndrome (SAS) in chronic heart failure (CHF) is not well known. The aim of our study was to find associated factors to SAS in heart failure (HF) and to look for differences between central sleep apnea (CSA) and obstructive sleep apnea (OSA)., Patients and Methods: We realised a cross-sectional and retrospective study. Thirty patients with stable heart failure under medical optimal therapy were included. Polygraphy, echocardiography and cardiopulmonary exercise were systematically performed., Results: Men were predominant (80%) in the group. Mean age, left ventricular ejection fraction (LVEF) were respectively 64.1±13.8years and 40±9.8%. SAS was present in 60% of patients (33.3% were classified as central sleep apnoea [CSA] and 26.7% as obstructive sleep apnoea [OSA]). Body mass index, blood pressure and left ventricular pressures estimated by the E/Ea ratio were significantly higher in the group with SAS (P<0.05) compared to the non SAS group. New York Heart Association class was significantly higher (P=0.04) and the predicted peak VO(2) was significantly lower in CSA patients compared to OSA patients., Conclusion: High left ventricular pressures estimated by the E/Ea are significantly associated with SAS in heart failure. CSA patients tend to have a worse functional state than OSA patients., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The association between diabetes mellitus and hypokinetic cardiomyopathy is frequent. We report a case of diabetes and hypokinetic cardiopathy in a 40-year-old man which led to the hypothesis of maternally inherited diabetes and deafness (MIDD) due to a mitochondrial disease. This diagnosis was confirmed by genetic testing which showed a DNA A3243G mutation in the mitochondria, the prevalence of which is 1-2% in diabetes mellitus. Cardiac abnormalities are frequent (18-34% of patients depending on the series) and the co-existence of left ventricular hypertrophy and systolic dysfunction is suggestive of this disease. Some authors have proposed co-enzyme Q as a treatment to improve the left ventricular ejection fraction and insulin secretion., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

We report two cases of cardiac pheochromocytoma, the first with superior vena cava obstruction and the second involving the left atrium and extending to the posterior wall of the aorta. Both tumors were resected with disease-free margins, with and without the use of cardiopulmonary bypass, respectively. The patients remain asymptomatic at 8-year and 1-year follow-ups, respectively., (Copyright 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We report the case of a patient referred to us for mitral and aortic valvular disease with a rheumatic appearance. The unusual macroscopic appearance on valve resection was not compatible with a rheumatic cause. A detailed review of this patient's clinical history (ie, a history of treatment with fenfluramine) suggested an iatrogenic cause, which was confirmed by histology. For the first time, a case of valvular heart disease that deteriorated was discovered 7 years after treatment with fenfluramine, whereas this iatrogenic disease classically resolves after discontinuation of treatment. This case illustrates the need for continuing heart valve surveillance of patients who have used these anorectics.

Background: Proximal tubule (PT) angiotensinogen (AGT) is part of a tubular renin-angiotensin system (RAS) that participates in the regulation of sodium reabsorption along the entire nephron. Physiologic maneuvers affecting AGT expression in PT also affect systemic RAS. Here, we tested the hypothesis that PT AGT is regulated by increased glomerular filtration rate (GFR)., Methods: Complete unilateral nephrectomy (UNX) in mice was used to induce a sustained increase in GFR in the remaining kidney. AGT expression was monitored by quantitative reverse transcription-polymerase chain reaction (RT-PCR). AGT protein in PT was investigated by semiquantitative histology. We also measured AGT concentration in plasma and in 24-hour urine by a specific enzyme-linked immunosorbent assay (ELISA)., Results: Seven weeks after nephrectomy, UNX animals exhibited a 2-fold increase in tubular AGT mRNA (P <.001) compared with sham-operated control animals. The proportion of PT sections exhibiting AGT immunostaining was significantly increased at day 3 (P <.05), and remained elevated at seven weeks (UNX = 0.63 +/- 0.09, sham = 0.38 +/- 0.02, P <.01), revealing recruitment of AGT-producing cells along the PT. AGT excretion in final urine corrected for creatinine and kidney weight was also elevated by UNX at seven weeks (UNX = 209 +/- 42 pmol/mg/g, sham = 147 +/- 29 pmol/mg/g, P <.05), with no difference in plasma AGT between UNX and control animals., Conclusion: These observations suggest that AGT expression in PT adapts in the long-term to changes in GFR. In the UNX model, urinary AGT excretion is also elevated as a consequence of increase in net tubular flow.

Background: The observation of renin expression in connecting tubule, a segment that also expresses tissue kallikrein (KLK-1), raises two questions. Are the genes expressed in the same or in different cells of connecting tubule? Does this topography support the hypothesis that KLK-1 activates prorenin or is it more likely that it affords coordinated gene regulation?, Methods: Renin and KLK-1 were examined by immunostaining and in situ hybridization. Renin activation by KLK-1 was investigated in vitro. In vivo, excretion of prorenin and active renin was compared in mice homozygous for targeted inactivation of KLK-1 (TK(-/-)) and normal littermates (TK(+/+))., Results: Using in situ immunostaining for renin and in situ hybridization for KLK-1 mRNA, we found that connecting tubule cells expressing renin also expressed KLK-1. We confirmed in vitro activation of prorenin by KLK-1, but found no difference in the ratio of active renin to prorenin in urine of TK(-/-) and TK(+/+) animals. Compared to TK(+/+) controls, TK(-/-) mice exhibited significantly lower 24-hour excretion of prorenin (5.05 +/- 1.16 mg Ang I/hour vs. 9.39 +/- 1.96 mg Ang I/hour, P < 0.05) and active renin (1.98 +/- 0.25 mg Ang I/hour vs. 3.58 +/- 0.39 mg Ang I/hour, P < 0.05), with no difference in either urine volumes or plasma renin concentrations., Conclusion: Direct interaction between renin and KLK-1, not ruled out in vitro, is not supported in vivo. By contrast, lower excretion of active renin and prorenin in TK(-/-) compared to TK(+/+) suggest coordinated regulation of the two proteins in their participation to collecting duct function.

BP measurement by a physician may trigger a blood pressure and heart rate increase often referred to as the white coat effect. This pressure response may occur both in normotensive and hypertensive subjects. The identification of such individuals is usually not possible on a clinical basis. This identification is however important because white coat effect and permanent hypertension do not share the same prognosis, the white coat effect being associated with a low rate of cardiovascular complications. To avoid an important overestimation of the real blood pressure level due to this white coat effect, it is possible to increase the delay before blood pressure measurements (beyond 15 minutes) or to take into account measurements made by nurses. Reading may also have a favorable consequence. However, a blood pressure recording outside the office, that is an ambulatory or a home blood pressure measurement, is the only way to confirm the presence of a white coat effect. The decision to treat is based on this measurement.

A 32-year-old pregnant woman with poor life and hygiene conditions presented with premature labour, fever and diarrhoea. After admission she gave birth to a stillborn child. The examination revealed a septicaemia with massive haemolysis and renal failure. Six blood cultures obtained on admission yielded Clostridium perfringens. The outcome was favourable after an adapted antibiomicrobial therapy. This case illustrates the potential severity of Clostridium perfringens foodborne toxi-infection which can lead to abortion and septicaemia with massive haemolysis.