Prognostic value of forward flow indices in primary mitral regurgitation due to mitral valve prolapse.

Background: Degenerative mitral regurgitation (DMR) due to mitral valve prolapse (MVP) is a common valve disease associated with significant morbidity and mortality. Timing for surgery is debated for asymptomatic patients without Class I indication, prompting the search for novel parameters of early left ventricular (LV) systolic dysfunction. Aims: To evaluate the prognostic impact of preoperative forward flow indices on the occurrence of post-operative LV systolic dysfunction. Methods: We retrospectively included all consecutive patients with severe DMR due to MVP who underwent mitral valve repair between 2014 and 2019. LVOTTVI, forward stroke volume index, and forward LVEF were assessed as potential risk factors for LVEF <50% at 6 months post-operatively. Results: A total of 198 patients were included: 154 patients (78%) were asymptomatic, and 46 patients (23%) had hypertension. The mean preoperative LVEF was 69 ± 9%. 35 patients (18%) had LVEF ≤ 60%, and 61 patients (31%) had LVESD ≥40 mm. The mean post-operative LVEF was 59 ± 9%, and 21 patients (11%) had post-operative LVEF<50%. Based on multivariable analysis, LVOTTVI was the strongest independent predictor of post-operative LV dysfunction after adjustment for age, sex, symptoms, LVEF, LV end systolic diameter, atrial fibrillation and left atrial volume index (0.75 [0.62-0.91], p < 0.01). The best sensitivity (81%) and specificity (63%) was obtained with LVOTTVI ≤15 cm based on ROC curve analysis. Conclusion: LVOTTVI represents an independent marker of myocardial performance impairment in the presence of severe DMR. LVOTTVI could be an earlier marker than traditional echo parameters and aids in the optimization of the timing of surgery.

Genetic and phenotypic continuum of HOXA genes: A case with double HOXA9/HOXA13 mutations.

The HOXA genes cluster plays a key role in embryologic development. Mutations in HOXA genes have been linked to different human phenotypes, including developmental delay, limb anomalies, and urogenital malformations. The present study reported a clinical and genetic investigation of a female patient with polymalformative syndrome including left arm agenesis, bicornuate uterus and bicuspid aortic valve. Using whole exome sequencing, two heterozygous missense variants were identified. Of these, one was a novel variant in the HOXA13 gene [p.(Tyr290Ser)] and the second a heterozygous variant in the HOXA9 gene [p.(Ala102Pro)]. To the best of our knowledge, this is the first association of HOXA9/HOXA13 point mutations linked to a syndromic case. In conclusion, the present study suggested that the phenotypic spectrum of vertebral anomalies, anal atresia, cardiac defects, tracheo­esophageal fistula, renal anomalies and limb abnormalities/hand­foot­genital syndrome may be attributable to the combination of different HOXA variants, particularly in patients with a severe clinical presentation. The current report contributed as well to the molecular understanding of HOXA genes­related phenotypes via the identification of novel variant and genes associations.

Clinical insights into a tertiary care center cohort of patients with bicuspid aortic valve.

Although bicuspid aortic valve (BAV) is one of the most common congenital heart diseases, clinical data associated with valve dysfunction are still limited. We evaluated clinical characteristics and echocardiography of French patients with BAV associated with leaking and stenosis degeneration. We initiated a prospective registry from 2014 to 2018 at a tertiary center. A total of 223 patients (168 males [75%], age 53 ± 17 years) were enrolled. Among these patients 83% had left-right coronary cusps fusion, 80% Sievers type 1 BAV and 49% showed aortic dilatation. Twenty-four patients (11%) had normal valve function, 66 patients (31%) had aortic stenosis (AS), 91 patients (41%) had aortic regurgitation (AR) and 40 patients (17%) had AR and AS. BAV phenotype did not predict neither AS nor AR (all p > 0.1). By multivariable analysis, age > 50 (41.6[10.3-248.2], p < 0.001) and presence of raphe/fusion (12.8[2.4-87.4], p < 0.001) were significantly associated with AS, whereas male gender was associated with AR (5[1.6-16.4], p = 0.005). In addition, leaking degeneration was observed at a much younger age than stenosis (44 ± 14 years vs. 66 ± 10 years, p < 0.01) and among patients with valve dysfunction younger age was independently associated with AR (1.9[1.85-1.94], p < 0.001). In this study we confirmed high prevalence of valve dysfunction at first diagnosis of BAV in a referred population. The degenerative process differs according to type of dysfunction and is mainly dependent on age and gender.

Prognostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Infective Endocarditis.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is commonly used for the diagnosis of infective endocarditis (IE), but its prognostic value remains unknown. OBJECTIVES: This study sought to assess the prognostic value of 18F-FDG PET/CT in prosthetic valve endocarditis (PVE) and native valve endocarditis (NVE). METHODS: This study prospectively included 173 consecutive patients (109 PVE and 64 NVE) with definite left-sided IE who had an 18F-FDG PET/CT and were followed-up for 1 year. The primary endpoint was a composite of major cardiac events: death, recurrence of IE, acute cardiac failure, nonscheduled hospitalization for cardiovascular indication, and new embolic event. RESULTS: 18F-FDG PET/CT was positive in 100 (58%) patients, 83% (n = 90 of 109) in the PVE, and 16% (n = 10 of 64) in the NVE group. At a mean follow-up of 225 days (interquartile range: 199 to 251 days), the primary endpoint occurred in 94 (54%) patients: 63 (58%) in the PVE group and 31 (48%) in the NVE group. In the PVE group, positive 18F-FDG PET/CT was significantly associated with a higher rate of primary endpoint (hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.1 to 6.7; p = 0.04). Moderate to intense 18F-FDG valvular uptake was also associated with worse outcome (HR: 2.3; 95% CI: 1.3 to 4.5; p = 0.03) and to new embolic events in PVE (HR: 7.5; 95% CI: 1.24 to 45.2; p = 0.03) and in NVE (HR: 8.8; 95% CI: 1.1 to 69.5; p = 0.02). In the NVE group, 18F-FDG PET/CT was not associated with occurrence of the primary endpoint CONCLUSIONS: In addition to its good diagnostic performance, 18F-FDG PET/CT is predictive of major cardiac events in PVE and new embolic events within the first year following IE.

Long-term results of surgical treatment of secondary severe mitral regurgitation in patients with end-stage heart failure: Advantage of prosthesis insertion.

BACKGROUND: Surgical treatment of secondary mitral regurgitation (SMR) is controversial. AIM: To analyse outcome after undersizing annuloplasty (UA) and mitral valve replacement (MVR). METHODS: Consecutive patients operated on for severe SMR, with left ventricular ejection fraction (LVEF)<40% and refractory CHF, were included. Endpoints were in-hospital mortality, mid-term cardiovascular (CV) mortality, evolution of LV variables and recurrence of mitral regurgitation (MR). RESULTS: 59 patients were included (mean age 65±10 years, preoperative LVEF 36±6%; effective regurgitant orifice [ERO] 41±17 mm2), 41 with ischaemic disease: 12 underwent UA and 47 underwent MVR; only eight had concomitant coronary revascularization. In-hospital mortality was 3.3% (8.3% in UA group; 2.1% in MVR group). Eight-year CV mortality was 39±13% (40±18% in UA group; 27±10% in MVR group). Older age (hazard ratio 1.14, 95% confidence interval 1.07 to 1.22; P<0.001) and LV end-systolic diameter (hazard ratio 1.18, 95% confidence interval 1.09 to 1.27; P<0.001) independently predicted CV mortality. LVEF did not change between the preoperative and follow-up transthoracic echocardiograms in the MVR group (36±6% vs. 35±10%; P=0.6) or the UA group (36±5% vs. 31±12%; P=0.09). Conversely, LV end-diastolic diameter decreased significantly in the MVR group (64±8m to 59±9mm; P=0.002), but not in the UA group (61±7m to 64±10mm; P=0.2). Recurrence of significant MR occurred in 81% of patients in the UA group (mean postoperative ERO 19±6 mm2) versus none in the MVR group. CONCLUSIONS: Surgical treatment of SMR can be performed with acceptable operative risk and mid-term survival in severe heart failure, even if there is no indication for revascularization. MVR is associated with significant reverse remodelling, and UA with prohibitive risk of MR recurrence.

Utility of stress perfusion-cardiac magnetic resonance in follow-up of patients undergoing percutaneous coronary interventions of the left main coronary artery.

To assess the accuracy of cardiac magnetic resonance (CMR) for the diagnosis of angiographic stenosis after percutaneous coronary intervention (PCI) of left main coronary artery (LMCA). Patients undergone in the last year PCI of unprotected LMCA and scheduled for conventional X-ray coronary angiography (CXA) were evaluated with stress perfusion CMR within 2 weeks before CXA. Main contraindications to CMR were exclusion criteria. Stress perfusion CMR was performed to follow a bolus of contrast Gadobutrol after 3 min of adenosine infusion. Between the 50 patients enrolled, only 1 did not finish the CMR protocol and 49 patients with median age 71 (65-75) years (38 male, 11 female) were analyzed. Between 784 coronary angiographic segments evaluated we found 75 stenosis or occlusions (prevalence 9.5%), but only 13 stenosis or occlusions in proximal segments (prevalence 6.6%). Patients with coronary stenosis (n = 12, 24%) showed a significantly (p = 0.002) higher prevalence of diabetes (7 of 12, 58%). At CMR examination, late gadolinium enhancement was present in 25 (51%), reversible perfusion defects in 12 (24%), and fixed perfusion defects in 6 subjects (12%). The only patient with LMCA restenosis resulted positive at perfusion CMR. The accuracy of stress perfusion CMR in diagnosis of coronary stenosis was higher when the analysis was performed only in proximal coronary arteries (95%, CI 86-99) compared to overall vessels (84%, CI 70-92). Stress perfusion CMR could strongly reduce the need for elective CXA in follow up of LMCA PCI and should be validated in further multicenter prospective studies.

Long-term prognostic role of cerebrovascular disease and peripheral arterial disease across the spectrum of acute coronary syndromes.

BACKGROUND: In acute coronary syndromes (ACS), the influence of cerebro-vascular disease (CVD) and/or peripheral artery disease (PAD) on short-midterm outcome has been well established. Data on long-term outcome however, are limited. Our study aimed to explore the effect of CVD and PAD on long-term outcome in a cohort of unselected ACS patients, including ST-elevation (STE-ACS) and non-ST-elevation (NSTE-ACS). METHODS AND RESULTS: The population consisted of 2046 consecutive patients with a confirmed final diagnosis of ACS; 896 (44%) had STE-ACS and 1150 (66%) NSTE-ACS. CVD alone was present in 98 patients (5%), 282 (14%) had PAD alone, and 30 (1.5%) had both. All cause mortality at 5 years was lowest in patients without CVD/PAD (33%), intermediate in patients with either CVD or PAD (62% and 63%, respectively) reaching 80% in those with both CVD and PAD. These findings were confirmed in the STE-ACS and NSTE-ACS subgroups. CVD and PAD remained independent predictors of mortality after multivariable analysis, the combined presence of both carrying the highest risk within each ACS type (HR 4.15, 95% CI 1.83-9.44 for STE-ACS; HR 2.14, 1.29-3.54 for NSTE-ACS). Patients with CVD and/or PAD were less likely to be treated invasively and received less evidence-based treatment at discharge. CONCLUSIONS: Across the spectrum of ACS, extracardiac vascular disease harbors a negative long-term prognosis that worsens progressively with the number of affected arterial beds.

Troponin T elevation in acute aortic syndromes: Frequency and impact on diagnostic delay and misdiagnosis.

AIMS: Despite troponin assay being a part of the diagnostic work up in many conditions with acute chest pain, little is known about its frequency and clinical implications in acute aortic syndromes (AASs). In our study we assessed frequency, impact on diagnostic delay, inappropriate treatments, and prognosis of troponin elevation in AAS. METHODS AND RESULTS: Data were collected from a prospective metropolitan AAS registry (398 patients diagnosed between 2000 and 2013). Cardiac troponin test, using either standard or high sensitivity assay, was performed according to standard protocol used in chest pain units. Troponin T values were available in 248 patients (60%) of the registry population; the overall frequency of troponin positivity was 28% (ranging from 16% to 54%, using standard or high sensitivity assay respectively, p = 0.001). Troponin positivity was frequently associated with acute coronary syndromes (ACS)-like electrocardiogram findings, and with a twofold increased risk of long in-hospital diagnostic time (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.05-3.52, p = 0.03). The combination of positive troponin and ACS-like electrocardiogram abnormalities resulted in a significantly increased risk of in-hospital delay/coronary angiography/antithrombotic therapy due to a misdiagnosis of ACS (OR 2.48, 95% CI 1.12-5.54, p = 0.02). However, troponin positivity was not associated with in-hospital mortality (OR 1.63, 95% CI 0.86-3.10, p = 0.131). CONCLUSIONS: Troponin positivity was a frequent finding in AAS patients, particularly when a high sensitivity assay was employed. Abnormal troponin values were strongly associated with ACS-like electrocardiogram findings and with in-hospital diagnostic delay but apparently they did not influence in-hospital mortality.

Acute heart failure in patients with acute aortic syndrome: pathophysiology and clinical-prognostic implications.

AIMS: Although acute heart failure (AHF) is a potential complication of acute aortic syndromes (AAS), its clinical details and management implications have been scarcely evaluated. This study aimed to assess prevalence, pathophysiological mechanisms, impact on treatment, and in-hospital mortality of AHF in AAS. METHODS AND RESULTS: Data were collected from a prospective AAS registry (398 patients diagnosed between 2000 and 2013). Patients with AHF were identified by the presence of dyspnoea as the presentation symptom or radiological signs of pulmonary congestion or cardiogenic shock, including patients with cardiac tamponade (CT). AHF frequency was 28% (Stanford type A 32% vs. type B 20%, P = 0.01). Four mechanisms leading to AHF were identified, alone or in combination: CT (26%), aortic regurgitation (25%), myocardial ischaemia (17%), and hypertensive crisis (10%). In type A patients, aortic regurgitation and CT were the most frequent mechanisms, whereas myocardial ischaemia and hypertensive crisis were the most frequent in type B patients. Although no difference was noted for diagnostic times, AHF at presentation led to a longer surgical delay in type A AAS. In-hospital mortality was higher in patients with AHF compared with those without (34% vs. 17%, P < 0.001). After multivariable analysis, AHF was associated with increased risk of in-hospital death (adjusted odds ratio 1.97, 95% confidence interval 1.14-3.36, P = 0.014). CONCLUSION: AHF occurs in more than a quarter of patients with AAS of both type A and type B, is due to a variety of pathophysiological mechanisms, and is associated with increased surgical delay and in-hospital mortality.

Long-term outcomes and causes of death after acute coronary syndrome in patients in the Bologna, Italy, area.

We sought to evaluate the rates, time course, and causes of death in the long-term follow-up of unselected patients with acute coronary syndromes (ACS). We enrolled 2046 consecutive patients hospitalized from January 2004 to December 2005 with an audited final diagnosis of ACS. The primary study end point was 5-year all-cause mortality. In our series, 896 patients had ST-segment elevation (STE) and 1,150 non-ST-segment elevation (NSTE). Mean age of the study population was 71.6 years. Primary percutaneous coronary intervention was performed in 86% of STE-ACS, and 70% of NSTE-ACS was managed invasively. The 5-year all-cause mortality was 36.4% for STE-ACS and 42.0% for NSTE-ACS, with patients with STE-ACS showing a trend boarding statistical significance toward a lower risk of mortality (hazard ratio [HR] = 0.88, 95% confidence interval [CI] 0.76 to 1.02, p = 0.08). Landmark analysis demonstrated that patients with STE-ACS had a higher risk of 30-day mortality (STE-ACS vs NSTE-ACS HR = 1.53, 95% CI 1.16 to 2.06, p = 0.003) whereas the risk of NSTE-ACS increased markedly after 1 year (STE-ACS vs NSTE-ACS HR = 0.67, 95% CI 0.53 to 0.84, p = 0.001). The contribution of noncardiovascular (CV) causes to overall mortality increased from 3% at 30 days to 34% at 5 years, with cancer and infections being the most common causes of non-CV death both in STE-ACS and NSTE-ACS. In conclusion, long-term mortality after ACS is still too high both for STE-ACS and NSTE-ACS. Although patients with STE-ACS have a higher mortality during the first year, the mortality of patients with NSTE-ACS increases later, when non-CV co-morbidities gain greater importance.

Impact of high-sensitivity Troponin T on hospital admission, resources utilization, and outcomes.

AIMS: The use of high-sensitivity cardiac Troponin T (hs-cTnT) assay might lead to overdiagnosis and overtreatment of Acute Coronary Syndromes (ACS). This study assessed the epidemiological, clinical and prognostic impact of introducing hs-cTnT in the everyday clinical practice of an Emergency Department. METHODS AND RESULTS: We compared all consecutive patients presenting with suspected ACS at the Emergency Department, for whom troponin levels were measured. In particular, we considered 597 patients presenting during March 2010, when standard cardiac Troponin T (cTnT) assay was used, and 629 patients presenting during March 2011, when hs-cTnT test was used. Patients with suspected ACS and troponin levels above the 99th percentile (Upper Reference Limit, URL) significantly increased when using an hs-cTnT assay (17.2% vs. 37.4%, p< 0.001). Accordingly, also the mean GRACE risk score increased (124.2 ± 37.2 vs. 136.7 ± 32.2; p< 0.001). However, the final diagnosis of Acute Myocardial Infarction (AMI) did not change significantly (8.7% vs. 6.8%, p=0.263) by using a rising and/or falling pattern of hs-cTnT (change ≥ 50% or ≥ 20% depending on baseline values). In addition, no significant differences were found between the two study groups with respect to in-hospital (2.7% vs. 1.9%, p=0.366) and 1-year mortality (9.8% vs. 7.6%, p=0.216). CONCLUSIONS: We did not observe overdiagnosis and overtreatment issues in presenters with suspected ACS managed by appropriate changes in hs-cTnT levels, despite the increase in the number of patients presenting with abnormal troponin levels. This occurred without a rise in short-term and mid-term mortality.