Summary 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.
The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for ...resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control.
One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients.
The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients.
In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.
Intravenous mineralocorticoid receptor antagonists (MRAs) have been used in some centers for decades to reduce the risk of hypokalemia and boost diuresis in acutely decompensated heart failure ...(ADHF). We report the well-tolerated use of intravenous MRAs as a rescue procedure in 3 patients admitted for ADHF with important diuretic resistance. Undertaking trials evaluating the effect of this therapeutic strategy in ADHF could represent a promising avenue.
Objectives
To assess the diagnostic performances of chest CT for triage of patients in multiple emergency departments during COVID-19 epidemic, in comparison with reverse transcription polymerase ...chain reaction (RT-PCR) test.
Method
From March 3 to April 4, 2020, 694 consecutive patients from three emergency departments of a large university hospital, for which a hospitalization was planned whatever the reasons, i.e., COVID- or non-COVID-related, underwent a chest CT and one or several RT-PCR tests. Chest CTs were rated as “Surely COVID+,” “Possible COVID+,” or “COVID−” by experienced radiologists. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the final RT-PCR test as standard of reference. The delays for CT reports and RT-PCR results were recorded and compared.
Results
Among the 694 patients, 287 were positive on the final RT-PCR exam. Concerning the 694 chest CT, 308 were rated as “Surely COVID+”, 34 as “Possible COVID+,” and 352 as “COVID−.” When considering only the “Surely COVID+” CT as positive, accuracy, sensitivity, specificity, PPV, and NPV reached 88.9%, 90.2%, 88%, 84.1%, and 92.7%, respectively, with respect to final RT-PCR test. The mean delay for CT reports was three times shorter than for RT-PCR results (187 ± 148 min versus 573 ± 327 min,
p
< 0.0001).
Conclusion
During COVID-19 epidemic phase, chest CT is a rapid and most probably an adequately reliable tool to refer patients requiring hospitalization to the COVID+ or COVID− hospital units, when response times for virological tests are too long.
Key Points
•
In a large university hospital in Lyon
,
France
,
the accuracy
,
sensitivity
,
specificity
,
PPV
,
and NPV of chest CT for COVID-19 reached 88.9
%,
90.2
%,
88
%,
84.1
%,
and 92.7
%,
respectively
,
using RT-PCR as standard of reference.
•
The mean delay for CT reports was three times shorter than for RT-PCR results
(
187
±
148 min
versus
573
±
327 min
,
p
<
0.0001
).
•
Due to high accuracy of chest CT for COVID-19 and shorter time for CT reports than RT-PCR results
,
chest CT can be used to orient patients suspected to be positive towards the COVID
+
unit to decrease congestion in the emergency departments.
The aim was threefold: 1) expound the independent physiological parameters that drive FFR, 2) elucidate contradictory conclusions between fractional flow reserve (FFR) and coronary flow reserve ...(CFR), and 3) highlight the need of both FFR and CFR in clinical decision making. Simple explicit theoretical models were supported by coronary data analyzed retrospectively.
FFR was expressed as a function of pressure loss coefficient, aortic pressure and hyperemic coronary microvascular resistance. The FFR-CFR relationship was also demonstrated mathematically and was shown to be exclusively dependent upon the coronary microvascular resistances. The equations were validated in a first series of 199 lesions whose pressures and distal velocities were monitored. A second dataset of 75 lesions with pre- and post-PCI measures of FFR and CFR was also analyzed to investigate the clinical impact of our hemodynamic reasoning.
Hyperemic coronary microvascular resistance and pressure loss coefficient had comparable impacts (45% and 49%) on FFR. There was a good concordance (y = 0.96 x - 0.02, r2 = 0.97) between measured CFR and CFR predicted by FFR and coronary resistances. In patients with CFR < 2 and CFR/FFR ≥ 2, post-PCI CFR was significantly >2 (p < 0.001), whereas it was not (p = 0.94) in patients with CFR < 2 and CFR/FFR < 2.
The FFR behavior and FFR-CFR relationship are predictable from basic hemodynamics. Conflicting conclusions between FFR and CFR are explained from coronary vascular resistances. As confirmed by our results, FFR and CFR are complementary; they could jointly contribute to better PCI guidance through the CFR-to-FFR ratio in patients with coronary artery disease.
Purpose of Review
The identification of BRAF mutation prompted the development of new class of targeted therapy for treating melanoma: BRAF inhibitors and MEK inhibitors. Cardiovascular events have ...been reported with these treatments and could counterbalance their long-term maintenance.
Recent Findings
LVEF decrease due to BRAF and MEK inhibitors appears fairly common (10%) but usually not severe, without impact on patient outcomes. To date, no treatment options have been tested to prevent or to treat a decrease of LVEF associated with BRAF and MEK inhibitors. QTc prolongation was observed in 3% and arterial hypertension in 20% during treatment but only one-third of cases required a therapeutic change.
Summary
BRAF and MEK inhibitors have revolutionized the management and the prognosis of melanoma patients. Cardio-oncology units may be useful for a better care of potential cardiac toxicity and particularly to inappropriately avoid discontinuing BRAF and MEK inhibitors.
Abstract 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.
Data on optimal antiplatelet therapy in patients undergoing stenting of the proximal left anterior descending artery (LAD) are limited.
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.
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; Pinteraction = 0.951). However, the risk of any MI (2.63% vs. 3.88%; HR:0.68; 95% CI:0.47–0.97; Pinteraction = 0.015) and any revascularization (7.84% vs. 9.94%; HR:0.78; 95% CI:0.63–0.97; Pinteraction = 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; Pinteraction = 0.981).
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.
•The proximal LAD segment has been considered at a higher risk for adverse events.•Few studies have evaluated optimal antiplatelet regimens in this specific cohort.•Ticagrelor monotherapy reduced ischemic risks in patients with stenting to proximal LAD.•These favourable benefits were achieved without an increased risk of major bleeding.
Background
Although aortic stiffness assessed by pulse wave velocity (PWV) is a strong predictor of coronary artery disease, the significance of local coronary stiffness has never been tackled. The ...first objective of this study was to describe a method of measuring coronary PWV (CoPWV) invasively and to describe its determinants. The second objective was to assess both CoPWV and aortic PWV in patients presenting with acute coronary syndromes or stable coronary artery disease.
Methods and Results
In 53 patients, CoPWV was measured from the delay in pressure wave and distance traveled as a pressure wire was withdrawn from the distal to the proximal coronary segment. Similarly, aortic PWV was measured invasively when the wire was pulled across the ascending aorta; carotid–femoral PWV was also measured noninvasively using the SphygmoCor system (AtCor Medical). Mean CoPWV was 10.3±6.1 m/s. Determinants of increased CoPWV were fractional flow reserve, diastolic blood pressure, and previous stent implantation in the recorded artery. CoPWV was lower in patients with acute coronary syndromes versus stable coronary artery disease (7.6±3 versus 11.5±6.4 m/s; P=0.02), and this persisted after adjustment for confounders. In contrast, aortic stiffness, assessed by aortic and carotid–femoral PWV, did not differ significantly.
Conclusions
CoPWV seems associated with acute coronary events more closely than aortic PWV. High coronary compliance, whether per se or because it leads to a distal shift in compliance mismatch, may expose vulnerable plaques to high cyclic stretch. CoPWV is a new tool to assess local compliance at the coronary level; it paves the way for a new field of research.
Transcatheter aortic valve replacement (TAVR) has now become a safe and effective alternative to surgery in patients with a contraindication or at high risk (2). Because patients considered for TAVR ...are elderly, implying that they often have a markedly remodeled aorta, the arterial component of the LV load is likely to be sizable; yet, the precise impact of aortic remodeling on cardiac outcomes after TAVR has never been tackled. In a first multivariable Cox regression model adjusted for arterial approach, peripheral artery disease, and previous coronary artery bypass grafting (or prevalence of coronary artery disease), AAC remained predictive of the outcome (tertiles 3 and 2 vs. 1 HR: 2.50; 95% CI: 1.23 to 5.09; p = 0.001; +1 Log increment of ACC HR: 1.70; 95% CI: 1.10 to 2.61; p = 0.016).
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