The natural history of a family with aortic dissection associated with a novel ACTA2 variant.

Disease-causing heterozygous variants in the ACTA2 gene cause an autosomal dominant heritable thoracic aortic disease (HTAD) with thoracic aortic aneurysm and dissection as main phenotype, and occasional extravascular abnormalities such as livedo reticularis. ACTA2-HTAD accounts for an important part of non-syndromic HTAD, with detection rates varying between 1.5-21% according to different studies. A consensus statement for the screening and management of patients with pathogenic ACTA2 variants has been recently published by the European reference network for rare vascular diseases (VASCERN). However, management of ACTA2 patients is often challenged by extremely variable inter- and intra-familial clinical courses of the disease. Here we report a family harboring a disease-causing ACTA2 variant. The proband and two siblings presented with acute type A aortic dissection and rupture involving nondilated aortic segments before the age of 30. Their mother died at 49 years-old from type B aortic dissection and rupture. Genetic testing revealed the heterozygous novel p.(Pro335Arg) variant in the ACTA2 gene in the proband and in the affected siblings. The clinical history of this family highlights the difficulty of adopting effective prevention strategies in ACTA2 patients.

Influence of nocturnal hypoxemia on follow-up course after type B acute aortic syndrome.

INTRODUCTION: Association between sleep nocturnal breathing disorders and acute aortic syndrome (AAS) has been described but mid-term data are scarce. OBJECTIVES: We assessed the prognostic value of sleep apnea parameters and their relationship with aortic morphology after the onset of a type B AAS. METHODS: Between January 2010 and January 2018, sleep apnea screening in post type B AAS was prospectively performed. The association of sleep apnea parameters with aortic morphology and aortic expansion during follow-up was studied. RESULTS: Over the 8-year-study period, 103 patients were included, with a mean age of 57.8 ± 12.1 years old. Median follow-up was 25.0 months (11.0-51.0). Thirty-two patients (31%) required aortic stenting during the acute phase. In patients treated by aortic stenting, the descending thoracic aortic diameter was positively associated with a higher percentage of nocturnal time of saturation ≤ 90% after adjustment (p = 0.016). During follow-up, the nocturnal time of saturation ≤ 90% in patients treated by medical therapy was the only parameter associated with significant aortic expansion rate (r = 0.26, p = 0.04). Thirty-eight patients started and sustained nocturnal ventilation during follow-up. The association between aortic expansion rate and nocturnal time of saturation ≤ 90% did not persist during follow-up after adjustment on nocturnal ventilation initiation (r = 0.25, p = 0.056). CONCLUSIONS: Nocturnal hypoxemia parameters are positively associated with the max onset aortic diameter and significant aortic growth after type B AAS. Nocturnal ventilation seems to mitigate aortic expansion during follow-up.

Aortic morphology post type A acute aortic syndrome: Prognosis significance and association with 24-hour blood pressure-monitoring parameters.

BACKGROUND: After an emergent surgery for type A acute aortic syndrome, medical management is based on optimal blood pressure (BP) control. We assessed the prognostic significance of BP monitoring and its relationship with aortic morphology following type A acute aortic syndrome. METHODS: The data of 120 patients who underwent BP monitoring after a type A acute aortic syndrome from January 2005 to June 2016 were retrospectively collected. The first CT angiogram performed after surgery was used for the morphological analysis. RESULTS: The population included 79 males, with an overall mean age of 60 ± 12 years. Seven patients (5.8%) died during a median follow-up of 5.5 years. The median delay between BP monitoring and discharge was 3 (1-5) months. The mean 24-hour BP of the cohort was 127/73 mm Hg ± 10/17. During follow-up, different parameters of BP monitoring were not associated with the risk of aortic events. However, the diameter of the false lumen of the descending thoracic aorta was the best predictor associated with the risk of new aortic events during follow-up, particularly for the threshold of 28 mm or more (P < .001; Hazard ratio 4.7[2.7-8.2]). The diameter of the false lumen was associated with night-time systolic BP (P = .025; r = .2), 24-hour pulse pressure (P = .002; r = .28), and night-time pulse pressure (P = .008; r = .24). CONCLUSION: The risk of new aortic events following type A acute aortic syndrome is associated with the size of the residual false lumen, but not directly with BP parameters. Night-time BP parameters are associated with the size of the residual false lumen.

Editor's Choice - Long-term Survival and Risk Analysis in 136 Consecutive Patients With Type B Aortic Dissection Presenting to a Single Centre Over an 11 Year Period.

OBJECTIVES: To evaluate, in patients with acute type B aortic dissection, the results of medical and endovascular treatment in a large single centre experience and to investigate the clinical and imaging features on presentation that relate to poor outcome. METHODS: This was a retrospective analysis of prospectively collected clinical and CT imaging data. Consecutive patients (136) with acute type B aortic dissection were included in the study over an 11 year period. The characteristics of patients receiving endovascular (complicated) or medical treatment (uncomplicated) were compared. Kaplan-Meier estimators were used to estimate cumulative overall survival and survival free of aortic events. Factors associated with overall and aortic event free survival were also explored using Cox proportional hazards models. RESULTS: The mean follow up was 51 months (1-132), during which time 33 deaths and 48 aortic events occurred. At one and five years, overall survival was 94.0% and 74.8%, respectively, and freedom from aortic events was 75.6% and 58.7%. There was no difference in all cause survival and aortic event free survival at one and five years between the patients treated endovascularly and those receiving medical treatment alone. Risk analysis for aortic events demonstrated the maximum size of the proximal entry tear, the maximum thoracic aortic diameter, and the thoracic aortic false lumen maximum diameter to have a significant effect on the incidence of aortic events. CONCLUSIONS: Active management of patients with type B aortic dissection results in good long-term survival even in the presence of features traditionally associated with adverse outcomes. All patients require close lifetime surveillance as aortic events continue to occur during follow up even after endografting.

Aortic root size is associated with nocturnal blood pressure in a population of hypertensive patients under treatment for obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with an increased aortic root size. This association has never been studied in patients with hypertension undergoing continuous positive airway pressure (CPAP) treatment for OSA. METHODS: The 24-h blood pressure (BP) monitoring of 142 hypertensive patients undergoing CPAP treatment for OSA was prospectively documented. Aortic root diameter was assessed by echocardiography. RESULTS: The population included 33.8% women, with an overall mean age of 60.7 ± 10.5 years. The median body mass index was 32.7 [29. 5-36.3] kg/m2. The median treatment score was 3 [2-4] anti-hypertensive drugs per day. The median 24-h systolic and diastolic BP were 130 [120-144] and 74.5 [69-82] mmHg, respectively. The night-time systolic and diastolic BP were 119.5 [108-136] and 67 [61-74] mmHg, respectively. The mean diameter of the aorta at the level of the Valsalva sinuses was 34.9 ± 4.4 mm and 20.4 ± 2.3 mm/m when adjusted for height. Patients underwent ventilation for a median duration of 3.8 [1. 7-7.5] years, with a median night-time duration of 6.6 [5. 5-7.5] h per night. The median residual apnea-hypopnea index under ventilation was 2 [1-4] events per hour. A multivariate analysis showed that aortic root size was associated with male gender (p < 0.01) and nocturnal diastolic BP (p < 0.01). When normalized for height, aortic root diameter was positively associated with age (p < 0.01) and nocturnal diastolic BP (p < 0.01). CONCLUSION: In OSA patients, the relationship between aortic root diameter and nocturnal BP persists on CPAP therapy. Further studies that evaluate the potential protective effect of OSA treatment on aortic root dilatation should monitor nocturnal diastolic BP.

Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial.

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.

Prognostic Significance of the Renal Resistive Index After Renal Artery Revascularization in the Context of Flash Pulmonary Edema.

PURPOSE: To evaluate the prognostic value of the renal resistive index (Ri) after renal artery revascularization in the context of flash pulmonary edema. METHODS: Between 2000 and 2008, 43 patients (mean age 72.1±10.9 years; 23 women) underwent renal artery angioplasty/stenting in the context of flash pulmonary edema. Intrarenal Ri was assessed using duplex ultrasound. The majority (97.7%) of patients had hypertension, and nearly half (46.5%) had diabetes mellitus. For this retrospective analysis, the patients were divided into 2 groups according to the median Ri (<0.8 and ≥0.8) of the population. A Cox proportional hazards model was used to identify predictors of all-cause mortality (primary endpoint) and rehospitalization for heart failure; the results are presented as the hazard ratio (HR) and 95% confidence interval (CI). The mean follow-up was 49.8±30.6 months. RESULTS: There was no difference between the groups regarding clinical characteristics. A high Ri was associated with the risk of all-cause death (HR 2.54, 95% CI 1.15 to 5.60, p=0.021). This relationship was still statistically significant after adjustment for age, gender, diabetes, glomerular filtration rate, and treatment with a renin-angiotensin system inhibitor (HR 1.74, 95%CI 1.08 to 2.81, p=0.032). A high Ri was also associated with cardiovascular death in unadjusted and adjusted analyses. In contrast, a high Ri was not associated with the risk of rehospitalization for heart failure. CONCLUSION: After renal artery revascularization for flash pulmonary edema, a high intrarenal Ri is independently associated with all-cause mortality. Determination of the intrarenal Ri after this procedure may be useful for identifying at-risk patients.

[Iatrogenic and drug-induced hypertension]. / Hypertensions artérielles médicamenteuses et toxiques.

Various toxic or drug agents can induce arterial hypertension, aggravate or limit the efficiency of anti-hypertensive drugs. Iatrogenic and drug-induced hypertension should be well known by the clinicians and the pharmacists, given the impact for driving the management of patients. In the food, an excessive alcohol consumption (more than 30 g per day) and more rarely glycerizine (active ingredient of the licorice) should be systematically looked for in front of a recent hypertension or do not respond to usual treatment. In the list of offending medicines, we must remember ethinyl estradiol contained in the contraception (oral, vaginal ring or transcutaneous patch), non steroidal anti-inflammatory drugs, immunosuppressants (cyclosporine, tacrolimus), vascular endothelial growth factor and its receptor R2 (avastin, inhibitors of receptor tyrosine kinases), recombinant human erythropoietin, sympathomimetics (nasal decongestants), anabolic steroids, bromocriptine (inhibitor of lactation), psychotropes (tricyclics antidepressants, monoamine oxydase inhibitors). The diagnosis of iatrogenic hypertensions should be systematically suspected in front of a suggestive clinical context with a meticulous food questioning because these hypertensions are partially or fully reversible after exposure stops.

Thrombocytopenia: an early marker of late mortality in type B aortic dissection.

Mid-term and long-term mortality after aortic dissection remain high and due to unknown factors. To determine predicting factors at the acute phase associated with mid- and long-term all-cause mortality, patients with type B aortic dissection including intramural hematoma, treated in one referral university center in an area with a population of 4 million, were analyzed over a period of 12 years (from 1996 to 2008). Based on the total population, 77 patients discharged after type B aortic dissection (including 11 intramural hematoma) were recorded as treated with either medical treatment alone (n = 41) or with additional endovascular therapy (n = 36). The mean follow-up period was 50.8 months, with a survival rate of 78 % (17 deaths). Patient history, symptoms, medical treatment, biological parameters, imaging, and intervention during acute phase (more than 150 parameters) were analyzed to identify any relationship with complications and death. Kaplan-Meier survival curve and Cox proportional hazards analyses identified independent predictors of follow-up mortality from any cause. Factors influencing mortality (P < 0.05) were a low systolic blood pressure (SBP) at admission, a thrombocytopenia in the acute period, chronic bronchitis, diameter of ascending aorta, and renin-angiotensin system inhibitor intake. Independent predictors of mortality were chronic bronchitis (P = 0.0022, hazard ratio (HR) 17.5), early thrombocytopenia (P = 0.042, HR 3.5), and admission SBP <120 mmHg (P = 0.0048, HR 7.928). Treated (medical ± endovascular) type B aortic dissection held a worse long-term prognosis, which can be correlated with predicting factors, especially in-hospital thrombocytopenia, and should require closer follow-up.

Feasibility and prognostic significance of ventricular-arterial coupling after myocardial infarction: the RIGID-MI cohort.

AIMS: The clinical significance and feasibility of the recently described non-invasive parameters exploring ventricular-arterial coupling (VAC) remain uncertain. This study aimed to assess VAC parameters for prognostic stratification in stable patients with left ventricular ejection fraction (LVEF) ≥40% following myocardial infarction (MI). METHODS AND RESULTS: Between 2018 and 2021, patients with LVEF ≥40% were evaluated 1 month following MI using transthoracic echocardiography (TTE) and arterial tonometry at rest and after a handgrip test. VAC was studied via the ratio between arterial elastance (Ea) and end-systolic LV elastance (Ees) and between pulse wave velocity (PWV) and global longitudinal strain (GLS). Patients were followed for major adverse cardiovascular events (MACE): all-cause death, acute heart failure, stroke, AMI, and urgent cardiovascular hospitalization. Among the 374 patients included, Ea/Ees and PWV/GLS were obtained at rest for 354 (95%) and 253 patients (68%), respectively. Isometric exercise was workable in 335 patients (85%). During a median follow-up of 32 months (interquartile range: 16-42), 41 (11%) MACE occurred. Patients presenting MACE were significantly older and had a higher prevalence of peripheral arterial disease, lower GLS, higher Ea, PWV, and PWV/GLS ratio. The Ea/Ees ratio and standard TTE parameters during isometric exercise were not associated with MACE. After adjustment, the PWV/GLS ratio was the only VAC parameter independently associated with outcome. Receiver operating characteristic curve analysis identified a PWV/GLS ratio >0.70 (Youden's index = 0.37) as the best threshold to identify patients developing MACE: hazard ratio (95% confidence interval) = 2.2 (1.14-4.27), P = 0.02. CONCLUSION: The PWV/GLS ratio, assessed 1 month after MI, identifies a group of patients at higher risk of MACE providing additional value on top of conventional non-invasive parameters.

Aortic dissection: results of the invasive treatment in France between 2012 and 2018 according to the French national database.

BACKGROUND: To evaluate results of the invasive repair in the management of acute aortic dissection (AoD) in France. METHODS: Patients admitted to hospital with acute AoD from 2012 to 2018 were identified. Patient demographics, severity score at admission, treatment strategy and in-hospital mortality were described. For patients undergoing intervention, perioperative complications rate was reported. A secondary analysis evaluating patients' outcome as regards of the annual caseload per center was conducted. RESULTS: Overall, 14,706 patients with acute AoD were identified (male 64%, mean age 67, median modified Elixhauser score 5). The overall incidence increased during the study period (from 3.8 in 2012 to 4.4/100,000 in 2018) associated with a North-South gradient (respectively 3.6 vs. 4.7/100,000) and a winter peak; 45.5% (N.=6697) of patients received medical treatment alone. Among those with invasive repair, 6276 (78.3%) were defined as type A AoD (TAAD), whereas type B AoD (TBAD) accounted for 1733 patients (21.7%), of whom 1632 (94%) had TEVAR and 101 (6%) had other arterial procedures; 30-day mortality was respectively 18.9% in TAAD and 9.5% for TBAD. In high-volume centers (i.e. >20 AoD/year), a lower 3-month mortality of 22.3% was noted compared to 31.4% in the low-volume centres (P<0.001); 47% of patients reported ≥1 early major complication. TEVAR exhibited less complication (P<0.001) compared to other arterial reconstructions in TBAD. CONCLUSIONS: The incidence of acute AoD increased in France over the period of the study and was associated with stable postoperative early mortality. Early postoperative mortality is significantly reduced in high-volume centers.

Relationship between accessory renal arteries and resistant hypertension: A cohort study.

BACKGROUND: Resistant hypertension (RHT) is a major health care concern affecting 20 to 30% of hypertensive patients and increasing cardiovascular risk. Recent renal denervation trials have suggested a high prevalence of accessory renal arteries (ARA) in RHT. Our objective was to compare the prevalence of ARA in RHT vs. non-resistant hypertension (NRHT). METHODS: Eighty-six patients with essential hypertension who benefited from an abdominal CT-scan or MRI during their initial workup were retrospectively recruited in 6 French ESH (European Society of Hypertension) centers. At the end of a follow-up period of at least 6 months, patients were classified between RHT or NRHT. RHT was defined as uncontrolled blood pressure despite the optimal doses of three antihypertensive agents of which one is a diuretic or similar, or controlled by ≥ 4 medications. Blinded independent central review of all radiologic renal artery charts was performed. RESULTS: Baseline characteristics were: age 50±15 years, 62% males, BP 145±22/87±13mmHg. Fifty-three (62%) patients had RHT and 25 (29%) had at least one ARA. Prevalence of ARA was comparable between RHT (25%) and NRHT patients (33%, P=0.62), but there were more ARA per patient in NRHT (2±0.9) vs. RHT (1.3±0.5, P=0.05), and renin levels were higher in ARA group (51.6±41.7 mUI/L vs. 20.4±25.4 mUI/L, P=0.001). ARA were similar in diameter or length between the 2 groups. CONCLUSIONS: In this retrospective series of 86 essential hypertension patients, we found no difference in the prevalence of ARA in RHT and NRHT. More comprehensive studies are needed to answer this question.

Contrast-enhanced ultrasound vs. CT angiography in fenestrated EVAR surveillance: a single-center comparison.

PURPOSE: To evaluate contrast-enhanced ultrasound (CEUS) as an effective alternative to computed tomographic angiography (CTA) during follow-up after fenestrated endovascular aneurysm repair (EVAR) of juxtarenal aortic aneurysms. METHODS: Between January 2008 and April 2011, 62 patients (all men; mean age 72 years) underwent fenestrated EVAR follow-up with both CTA and CEUS. In a retrospective analysis, the first CTA and CEUS postoperative examinations after EVAR were compared for endoleak detection, aneurysm sac diameter, and target vessel patency. The examinations were performed within 30 days of the procedure and the interval between the 2 scans was <7 days. Only fenestrated endografts with up to 3 fenestrations (with or without a scallop) were eligible so that the entire implant could be visualized with standard abdominal ultrasound. RESULTS: The mean diameters of the aneurysm sac were 56.58±8.56 mm with CEUS and 57.70±8.59 mm with CTA. The mean difference in aneurysm sac diameter was -1.13±3.19 mm (95% CI -0.34 to -1.92), with CTA measurements tending to be slightly larger. Bland-Altman plots showed good agreement between the imaging modalities with respect to aneurysm sac diameter (Spearman correlation coefficient r(s)=0.921, p<0.01). Endoleaks were detected by CTA in 7 (11.3%) of 62 patients and by CEUS in 6 (9.7%). In 59 (95.16%) cases, the tests agreed, and their equivalence was confirmed by binomial distribution testing. There was complete agreement between CEUS and CTA in the assessment of target vessels (144/146 patent target arteries; 1 had a significant stenosis and another was thrombosed). CONCLUSION: CEUS is as accurate as CTA in endoleak detection, abdominal aortic aneurysm diameter measurement, and the evaluation of target vessels during surveillance of fenestrated stent-grafts. Although it cannot yet be proposed as the only imaging modality during follow-up, CEUS could be usefully employed with the self-evident advantage of reducing lifetime exposure to ionizing radiation.

Prognostic significance of reverse dipping status on lower limb event in type 2 diabetic patients without peripheral arterial disease.

AIMS: We assessed reverse dipping influence on the risk of lower limb events in type 2 diabetic patients without peripheral arterial disease. METHODS: Patients with type 2 diabetes addressed for cardiovascular risk stratification in our university hospital from 2008 to 2012 underwent 24 h blood pressure monitoring. Patients with a prior history of limb revascularization or with a stenosis > 50% of the legs were excluded. Reverse dipping was defined as a greater night-versus day-time systolic blood pressure. The endpoint was the first occurrence of lower limb revascularization or limb amputation. Hazard ratios (HRs) and 95% confidence intervals were calculated using the Cox model. RESULTS: Two hundred and eighty-one patients were included. During a median follow-up of 9.4 [7.7-10.6] years, 20 lower limb events and 45 all-cause deaths were observed. Thirty-five patients were reverse dippers. The reverse dipping status was associated with lower limb events when considering all-cause death as a competitive risk, (HR 3.61 [1.16-11.2], P = 0.026). Reverse dipping, HbA1C and proteinuria were independently associated with lower limb outcome in a multivariable analysis (respectively HR 4.09 [1.29-12.9], P = 0.017, HR 1.30 [1.04-1.63], P = 0.022 and HR 1.06 [1.02-1.11], P = 0.001). CONCLUSIONS: Reverse dipping status is independently associated with worse limb outcome in type 2 diabetic patients.

Diabetes mellitus and cardiovascular mortality across the spectrum of aortic stenosis.

OBJECTIVE: Current data regarding the impact of diabetes mellitus (DM) on cardiovascular mortality in patients with aortic stenosis (AS) are restricted to severe AS or aortic valve replacement (AVR) trials. We aimed to investigate cardiovascular mortality according to DM across the entire spectrum of outpatients with AS. METHODS: Between May 2016 and December 2017, patients with mild (peak aortic velocity=2.5-2.9 m/s), moderate (3-3.9 m/s) and severe (≥4 m/s) AS graded by echocardiography were included during outpatient cardiology visits in the Nord-Pas-de-Calais region in France and followed-up for modes of death between May 2018 and August 2020. RESULTS: Among 2703 patients, 820 (30.3%) had DM, mean age was 76±10.8 years with 46.6% of women and a relatively high prevalence of underlying cardiovascular diseases. There were 200 cardiovascular deaths prior to AVR during the 2.1 years (IQR 1.4-2.7) follow-up period. In adjusted analyses, DM was significantly associated with cardiovascular mortality (HR=1.40, 95% CI 1.04 to 1.89; p=0.029). In mild or moderate AS, the cardiovascular mortality of patients with diabetes was similar to that of patients without diabetes. In severe AS, DM was associated with higher cardiovascular mortality (HR=2.65, 95% CI 1.50 to 4.68; p=0.001). This was almost exclusively related to a higher risk of death from heart failure (HR=2.61, 95% CI 1.15 to 5.92; p=0.022) and sudden death (HR=3.33, 95% CI 1.28 to 8.67; p=0.014). CONCLUSION: The effect of DM on cardiovascular mortality varied across AS severity. Despite no association between DM and outcomes in patients with mild/moderate AS, DM was strongly associated with death from heart failure and sudden death in patients with severe AS.

Prognostic values of exercise echocardiography and cardiopulmonary exercise testing in patients with primary mitral regurgitation.

AIMS: To compare the clinical significance of exercise echocardiography (ExE) and cardiopulmonary exercise testing (CPX) in patients with ≥moderate primary mitral regurgitation (MR) and discrepancy between symptoms and MR severity. METHODS AND RESULTS: Patients consulting for ≥moderate discordant primary MR prospectively underwent low (25 W) ExE, peak ExE, and CPX within 2 months in Lille and Rennes University Hospital. Patients with Class I recommendation for surgical MR correction were excluded. Changes in MR severity, systolic pulmonary artery pressure (SPAP), left ventricular ejection fraction (LVEF), and tricuspid annular plane systolic excursion were evaluated during ExE. Patients were followed for major events (ME): cardiovascular death, acute heart failure, or mitral valve surgery. Among 128 patients included, 22 presented mild-to-moderate, 61 moderate-to-severe, and 45 severe MR. Unlike MR variation, SPAP and LVEF were successfully assessed during ExE in most patients. Forty-one patients (32%) displayed reduced aerobic capacity (peak VO2 < 80% of predicted value) with cardiac limitation in 28 (68%) and muscular or respiratory limitation in the 13 others (32%). ME occurred in 61 patients (47.7%) during a mean follow-up of 27 ± 21 months. Twenty-five Watts SPAP [hazard ratio (HR) (95% confidence interval, CI) = 1.03 (1.01-1.06), P = 0.003] and reduced aerobic capacity [HR (95% CI) = 1.74 (1.03-2.95), P = 0.04] were independently predictive of ME, even after adjustment for MR severity. The cut-off of 55 mmHg for 25 W SPAP showed the best accuracy to predict ME (area under the curve = 0.60, P = 0.05). CONCLUSION: In patients with ≥moderate primary MR and discordant symptoms, 25 W exercise pulmonary hypertension, defined as an SPAP ≥55 mmHg, and poor aerobic capacity during CPX are independently associated with adverse events.

Clinical significance of myocardial work parameters after acute myocardial infarction.

Aims: To investigate the additional prognostic value of myocardial work (MW) parameters following acute myocardial infarction (AMI). Methods and results: Between 2018 and 2020, 244 patients admitted in the cardiac intensive care unit in Lille University Hospital for AMI were included. One-month following AMI, comprehensive transthoracic echocardiography (TTE) was performed to assess parameters of myocardial function. Patients were then followed for major events (ME): cardiovascular death, heart failure, and unplanned coronary revascularization. At 1-month, half of the population was symptomatic (NYHA ≥ II), and medical therapy was almost optimized (angiotensin-converting enzyme inhibitor/angiotensin 2 receptor blocker in 95.5%, beta-blockers in 96.3%, DAPT in 94.7%, and statins in 97.1%). After a median follow-up of 681 (interquartile range: 538-840) days, ME occurred in 26 patients (10.7%). Patients presenting ME were older (65.5 ± 14.2 vs. 58.1 ± 12.1years, P = 0.005) with a higher prevalence of hypertension (65.4 vs. 36.2%, P = 0.004), more impaired left ventricular (LV) function as assessed by LV ejection fraction (P = 0.07), global longitudinal strain (P = 0.03), or MW parameters [P = 0.01 for global work efficiency (GWE)], and greater LV and left atrium dilatations (P = 0.06 for left ventricular end-diastolic volume index and P = 0.03 for left atrial volume index). After adjustment, GWE was the only TTE parameter independently associated with long-term occurrence of ME (P = 0.02). A GWE value <91% was selected to identify patients at higher ME risk (hazard ratio: 95% confidence interval) = 2.94 (1.36-6.35), P = 0.0041). Conclusion: Lower GWE at 1 month after AMI is independently associated with higher ME rates. A GWE <91% can improve the post-AMI patient risk stratification.

Functional mitral regurgitation: a link to pulmonary hypertension in heart failure with preserved ejection fraction.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) may present with Pulmonary hypertension (PH) and functional mitral regurgitation (MR). Whether PH is linked to the presence of functional MR has not been investigated in HFpEF patients. METHODS AND RESULTS: Systolic pulmonary artery pressure (sPAP) and functional MR were assessed by 2-dimensional Doppler echocardiography in 70 ambulatory HFpEF patients and 70 hypertensive control subjects free of organic mitral valve lesions, significant valve disease, and comorbid conditions associated with PH. Whereas none of control subjects had more than trivial MR, 21 patients with HFpEF had functional MR (mean mitral effective regurgitant orifice, regurgitant volume, and regurgitant fraction 7 ± 3 mm,(2) 15 ± 8 mL, and 28 ± 14%, respectively). Pulmonary hypertension (sPAP >35 mm Hg) was significantly more prevalent in HFpEF patients with functional MR than in HFpEF patients without functional MR (62 vs 22%; P = .002). Functional MR remained an independent predictor of PH in HFpEF patients (P = .004) after adjustment on mitral E wave to e' mitral annulus velocity ratio (E/e'; P = .022) and left atrial volume index (P = .025). Systolic PAP and E/e' were greater in HFpEF patients than in control subjects (35 ± 9 vs 29 ± 8 mm Hg [P < .0001] and 13 ± 6 vs 11 ± 5 [P = .018], respectively). Systolic PAP remained greater in HFpEF patients than in control subjects after adjusting for E/e' (P = .002). CONCLUSIONS: Pulmonary hypertension appears to be linked to the presence of functional MR in HFpEF patients.