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Aims: Transthyretin cardiac amyloidosis (ATTR-CA) is a rare and progressive cardiomyopathy caused by amyloid fibril deposition in myocardial tissue. Diagnostic challenges have historically hampered timely detection. Recent advances in noninvasive diagnostic techniques have facilitated ATTR-CA diagnosis. We aimed to examine the development of a regional network for the diagnosis and management of ATTR-CA and describe a cohort of patients with ATTR-CA, investigate diagnostic pathways and assess clinical outcomes according to diagnosis periods., Methods: We performed a survey study analyzing answers from 11 cardiology centers and we conducted a retrospective study including patients with ATTR-CA attending a referral center between 1 January 2012 and 31 December 2022, and categorized by the period of diagnosis (2012-2016 and 2017-2022)., Results: Over the years, a growing number of patients reached a diagnosis and were treated in the surveyed nonreferral centers of the region. The retrospective study showed a more significant diagnostic delay in the earlier period rather than the later one [13.4 (5-30.2) vs. 10.6 (5.0-17.9) months, P = 0.04]. Patients diagnosed after 2017 showed a greater survival rate than those diagnosed earlier ( P = 0.02). In the multivariate analysis, the year of diagnosis from 2017 remained independently associated with mortality [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.28-0.79; P = 0.005]., Conclusion: This study emphasized the shift toward noninvasive diagnostic criteria. It revealed a positive impact on patient survival and disease management with the use of disease-modifying therapies and diagnostic developments in more recent years. The findings underscore the importance of disease awareness and networking to reduce diagnostic delays and enhance patient journeys for ATTR-CA., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Objective: The COVID-19 pandemic affected neuro-oncological patients and their caregivers regarding tumor care and emotional functioning, including Quality of Life (QoL). This study aimed to understand how COVID-19 affected their psychological state and the relations between patients and health personnel in neuro-oncology., Methods: A cross-sectional study was conducted on neuro-oncological patients and their caregivers., Results: A total of 162 patients and 66 caregivers completed the questionnaire. Altogether, 37.5% of patients perceived a greater risk of contracting COVID-19 compared to the general population. On a 0-10 scale, the patients' tumor-related anxiety score was 5.8, and their COVID-19-related score was 4.6. The caregivers reported 7.7 and 5.5, respectively. QoL was described as at least good in 75% of both patients and caregivers; the caregivers' care burden increased in 22.7% of cases during the pandemic, with no correlation with QoL. Future perception often changed, both in patients and caregivers. In 18% of cases, the cancer treatment schedule was changed, either by patient decision or by medical decision. However, 93.5% of patients were satisfied with their overall care., Conclusions: A considerable proportion of patients and caregivers still perceived the tumor disease as more burdensome than the pandemic, and their future as more uncertain. Such data suggest the need to build a productive alliance between patients and health professionals.

Background: Chronic kidney disease is common in patients admitted with acute coronary syndrome and its prevalence dramatically increases with age. Understanding the determinants of adverse outcomes in this extremely high-risk population may be useful for the development of specific treatment strategies and planning of secondary prevention modalities., Aim: The aim of this study was to assess the impact of baseline renal function and acute kidney injury on one-year outcome of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention., Methods: Patients aged 75 years and older with acute coronary syndrome undergoing successful percutaneous coronary intervention were selected among those enrolled in three Italian multicentre studies. Based on the baseline estimated glomerular filtration rate (eGFR) calculated using the Cockcroft-Gault formula ([(140-age) × body weight × 0.85 if female]/(72 × serum creatinine)* 1.73 m 2 of body surface area), patients were classified as having none or mild (eGFR ≥60 ml/min/1.73 m 2 ), moderate (eGFR 30-59 ml/min/1.73 m 2 ) or severe (eGFR <30 ml/min/1.73 m 2 ) renal dysfunction. Acute kidney injury was defined according to the Acute Kidney Injury Network classification. All-cause and cardiovascular mortality, non-fatal myocardial infarction, rehospitalisation for cardiovascular causes, stroke and type 2, 3 and 5 Bleeding Academic Research Consortium bleedings were analysed up to 12 months., Results: A total of 1904 patients were included. Of these, 57% had moderate and 11% severe renal dysfunction. At 12 months, patients with renal dysfunction had higher rates ( P  < 0.001) of all-cause (4.5%, 7.5% and 17.8% in patients with none or mild, moderate and severe renal dysfunction, respectively) and cardiovascular mortality (2.8%, 5.2% and 10.2%, respectively). After multivariable adjustment, severe renal dysfunction was associated with a higher risk of all-cause (hazard ratio (HR) 2.86, 95% confidence interval (CI) 1.52-5.37, P  = 0.001) and cardiovascular death (HR 3.11, 95% CI 1.41-6.83, P  = 0.005), whereas non-fatal events were unaffected. Acute kidney injury incidence was significantly higher in ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome patients (11.7% vs. 7.8%, P  = 0.036) and in those with reduced baseline renal function ( P  < 0.001), and it was associated with increased mortality independently from baseline renal function and clinical presentation., Conclusions: Baseline renal dysfunction is highly prevalent and is associated with higher mortality in elderly acute coronary syndrome patients undergoing percutaneous coronary intervention. Acute kidney injury occurs more frequently among ST-elevation myocardial infarction patients and those with pre-existing renal dysfunction and is independently associated with one-year mortality., (© The European Society of Cardiology 2020.)

Background: Worse outcomes have been reported for women, compared with men, after an acute coronary syndrome (ACS). Whether this difference persists in elderly patients undergoing similar invasive treatment has not been studied. We investigated sex-related differences in 1-year outcome of elderly acute coronary syndrome patients treated by percutaneous coronary intervention (PCI)., Methods: Patients 75 years and older successfully treated with PCI were selected among those enrolled in 3 Italian multicenter studies. Cox regression analysis was used to assess the independent predictive value of sex on outcome at 12-month follow-up., Results: A total of 2035 patients (44% women) were included. Women were older and most likely to present with ST-elevation myocardial infarction (STEMI), diabetes, hypertension, and renal dysfunction; men were more frequently overweight, with multivessel coronary disease, prior myocardial infarction, and revascularizations. Overall, no sex disparity was found about all-cause (8.3% vs 7%, P = .305) and cardiovascular mortality (5.7% vs 4.1%, P = .113). Higher cardiovascular mortality was observed in women after STEMI (8.8%) vs 5%, P = .041), but not after non ST-elevation-ACS (3.5% vs 3.7%, P = .999). A sensitivity analysis excluding patients with prior coronary events (N = 1324, 48% women) showed a significantly higher cardiovascular death in women (5.4% vs 2.9%, P = .025). After adjustment for baseline clinical variables, female sex did not predict adverse outcome., Conclusions: Elderly men and women with ACS show different clinical presentation and baseline risk profile. After successful PCI, unadjusted 1-year cardiovascular mortality was significantly higher in women with STEMI and in those with a first coronary event. However, female sex did not predict cardiovascular mortality after adjustment for the different baseline variables., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Whether balloon aortic valvuloplasty (BAV) may provide an effective palliation in symptomatic high-risk patients is uncertain. Therefore, we aimed to evaluate outcomes in symptomatic high-risk patients with severe aortic stenosis (AS), who underwent BAV. All-cause mortality and length of hospitalization for heart failure (HF) up to death or to 1-year follow up were collected after BAV. One hundred thirty-two (132) patients (62% women), mean age 85±7 years, underwent BAV with a substantial reduction of the peak-to-peak aortic gradient from 53±21 to 29±15 mmHg (p<0.001). The median of days of HF hospitalization prior to BAV was 9 (0-19), and decreased after BAV to 0 (0-9), p<0.001. During 1-year follow-up patients with untreated CAD (85, 64%) had a higher mortality compared to patients with insignificant/treated CAD (47, 36%): 1-year survival: 45±7% vs. 66± 7%; p=0.02. After adjustment for STS risk score and severity of residual AS, patients with untreated CAD remained at higher risk of mortality (adjusted HR 1.74 [1.01-2.91]; p=0.04). Thus, in this series of symptomatic high-risk patients, BAV was associated with a significant reduction in aortic valve gradient and hospitalization time for HF post-BAV. In patients with significant CAD, percutaneous intervention might be considered in order to improve survival.

Objective: Vasomotor symptoms (VMS) during menopausal transition have been linked to a higher burden of cardiovascular risk factors, subclinical vascular disease, and subsequent vascular events. We aim to investigate the association of VMS with the extent of coronary disease and their prognostic role after an acute coronary syndrome., Methods: The Ladies Acute Coronary Syndrome study enrolled consecutive women with an acute coronary syndrome undergoing coronary angiography. A menopause questionnaire was administered during admission. Angiographic data underwent corelab analysis. Six out of 10 enrolling centers participated in 1-year follow-up. Outcome data included the composite endpoint of all-cause mortality, recurrent myocardial infarction, stroke, and rehospitalization for cardiovascular causes within 1 year., Results: Of the 415 women with available angiographic corelab analysis, 373 (90%) had complete 1-year follow-up. Among them, 202 women had had VMS during menopausal transition. These women had the same mean age at menopause as those without VMS (50 years in both groups), but were younger at presentation (median age 71 vs 76 years; P < 0.001), despite a more favorable cardiovascular risk profile (chronic kidney dysfunction 4.5% vs 15.9%; P = 0.001; prior cerebrovascular disease 4.5 vs 12.2%; P = 0.018). Extent of coronary disease at angiography was similar between groups (mean Gensini score 49 vs 51; P = 0.6; mean SYNTAX score 14 vs 16; P = 0.3). Overall cardiovascular events at 1 year did not differ between groups (19% vs 22%; P = 0.5)., Conclusions: In postmenopausal women with an acute coronary syndrome, a history of VMS was associated with younger age at presentation, despite a lower vascular disease burden and similar angiographically defined coronary disease as compared with women without VMS. No difference could be found in terms of overall clinical outcomes. These results should be interpreted cautiously as all analyses were unadjusted and did not account for risk factor differences between women with and without a history of VMS.

Background: Early menopause has been associated with increased cardiovascular mortality, but prospective studies investigating outcomes of postmenopausal women with acute coronary syndromes (ACS) in relation to menopausal age are lacking., Methods: We analyzed the 1-year outcome of 373 women with acute myocardial infarction enrolled in the Ladies ACS study. All patients underwent coronary angiography, with corelab analysis. Menopause questionnaires were administered during admission. Menopausal age below the median of the study population (50 years) was defined as "early menopause". The composite 1-year outcome included all-cause mortality, recurrent myocardial infarction and stroke., Results: The mean age at index ACS was 73 years (IQR 65-83) for women with early menopause, and 74 (IQR 65-80) for those with late menopause. Patients with early menopause had more prevalent chronic kidney disease (12.8% vs 5.9%, p = 0.03), whereas there were no differences in all other clinical characteristics, extent of coronary disease at angiography (as assessed by Gensini and SYNTAX scores), as well as interventional treatments. Within 1 year, women with late menopause had significantly better outcome as compared with those with early menopause (6.5% vs 15.3%, p = 0.007). At logistic regression analysis, late menopause was independently associated with better outcome (OR 0.28; 95% CI 0.12-0.67; p = 0.004). With each year's delay in the menopause the adjusted risk decreased by 12% (OR 0.88, 0.77-0.99, p = 0.040)., Conclusion: Despite comparable clinical and angiographic characteristics, women with late menopausal age experience better outcomes after an ACS as compared with those with early menopause., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Epidemiological studies have shown a higher risk of cardiovascular mortality associated with early menopause, but the relation between menopausal age and extent of coronary artery disease after menopause is unknown. We assessed the relation between menopausal age and extent of coronary disease in postmenopausal women with an acute coronary syndrome., Methods: A prospective study was conducted in patients ≥55 years old undergoing coronary angiography for an acute coronary syndrome. Enrollment was stratified by sex (women/men ratio 2:1) and age (55-64, 65-74, 75-85, and >85 years). Women were administered menopause questionnaires during admission. An independent core lab quantified coronary artery disease extent using the Gensini Score, which classifies both significant (>50%) and nonsignificant lesions. Linear correlation was used to appraise the association between the Gensini score and menopausal age., Results: We enrolled 675 patients, 249 men and 426 women (mean age 74 years). The mean Gensini score was 60 ± 36 in men vs 50 ± 32 in women (P <.001), being higher among men at any age. The median menopausal age of women was 50 years. Risk factors and age at first acute coronary syndrome were identical among women below and above the median menopausal age. The Gensini score in women showed a weak association with age (R = 0.127; P = .0129), but not with menopausal age (R = 0.063; P = .228). At multivariable analysis, ejection fraction, female sex, and ST elevation myocardial infarction were independent predictors of the Gensini score in the overall population., Conclusions: Menopausal age was not associated with the extent of coronary artery disease. Age at first acute coronary syndrome presentation, risk factors, and prior cardiovascular events were not affected by menopausal age. (The LADIES ACS study: NCT01997307)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Liver transplantation (LT) has become the standard of care for patients with end stage liver disease. The allocation of organs, which prioritizes the sickest patients, has made the management of liver transplant candidates more complex both as regards their comorbidities and their higher risk of perioperative complications. Patients undergoing LT frequently display considerable physiological changes during the procedures as a result of both the disease process and the surgery. Transoesophageal echocardiography (TEE), which visualizes dynamic cardiac function and overall contractility, has become essential for perioperative LT management and can optimize the anaesthetic management of these highly complex patients. Moreover, TEE can provide useful information on volume status and the adequacy of therapeutic interventions and can diagnose early intraoperative complications, such as the embolization of large vessels or development of pulmonary hypertension. In this review, directed at clinicians who manage TEE during LT, we show why the procedure merits a place in challenging anaesthetic environment and how it can provide essential information in the perioperative management of compromised patients undergoing this very complex surgical procedure.

Background: Recurrent ST-segment elevations in acute coronary syndromes have been attributed to coronary cyclic flow variations (CCFVs) possibly due to coronary vasospasm and unstable platelet aggregation in partially occluded arteries., Methods: We describe the case of a patient with an acute myocardial infarction, recurrent ST-segment elevations and diffuse disease of the left anterior descending artery., Results: The post-angiography 12-lead continuous ECG monitoring revealed cyclic anterior ST-segment elevations that were completely abolished with continuous intravenous infusion of low-dose isosorbide-dinitrate., Conclusion: The complete and sustained response to low-dose nitrate suggests that vasoconstriction plays a crucial role to provoke CCFVs. This case underlines the importance of continuous 12-lead ECG monitoring with ST-segment trend analysis in the CCU., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) may coexist in elderly patients with a history of smoking. Low-grade systemic inflammation induced by smoking may represent the link between these 2 conditions. In this study, we investigated left ventricular dysfunction in patients primarily diagnosed with COPD, and nonreversible airflow limitation in patients primarily diagnosed with CHF. The levels of circulating high-sensitive C-reactive protein (Hs-CRP), pentraxin 3 (PTX3), interleukin-1β (IL-1 β), and soluble type II receptor of IL-1 (sIL-1RII) were also measured as markers of systemic inflammation in these 2 cohorts. Patients aged ≥ 50 years and with ≥ 10 pack years of cigarette smoking who presented with a diagnosis of stable COPD (n=70) or stable CHF (n=124) were recruited. All patients underwent echocardiography, N-terminal pro-hormone of brain natriuretic peptide measurements, and post-bronchodilator spirometry. Plasma levels of Hs-CRP, PTX3, IL-1 β, and sIL-1RII were determined by using a sandwich enzyme-linked immuno-sorbent assay in all patients and in 24 healthy smokers (control subjects). Although we were unable to find a single COPD patient with left ventricular dysfunction, we found nonreversible airflow limitation in 34% of patients with CHF. On the other hand, COPD patients had higher plasma levels of Hs-CRP, IL1 β, and sIL-1RII compared with CHF patients and control subjects (p < 0.05). None of the inflammatory biomarkers was different between CHF patients and control subjects. In conclusion, although the COPD patients had no evidence of CHF, up to one third of patients with CHF had airflow limitation, suggesting that routine spirometry is warranted in patients with CHF, whereas echocardiography is not required in well characterized patients with COPD. Only smokers with COPD seem to have evidence of systemic inflammation.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in men and women worldwide. The apparent cardioprotective effects of endogenous estrogens seem to prevent CVD in premenopausal women. Following menopause and loss of hormonal effects, gender-based differences in CVD are reduced, with the CVD risk being higher in women who develop the metabolic syndrome. In postmenopausal women, many features of the metabolic syndrome emerge with estrogen deficiency. Estrogen deficiency occurring in the menopausal period is associated with 1) dyslipidemia (hypertriglyceridemia, reduced HDL, and increased small dense LDL particles); 2) insulin resistance; 3) hypertension; 4) increased central fat and reduction in lean body mass; and 5) increased hypercoagulability and pro-inflammatory state. In addition to traditional cardiovascular risk factors, also early menopause has a negative impact on females. Over the past years, different approaches were found to improve quality of life and cardiovascular health in menopausal women. Since the concept of hormone replacement therapy (HRT), large observational studies and randomized clinical trials have amassed a wealth of data about the effects of menopause and the safety and efficacy of using estrogen replacement therapies to treat menopause symptoms and menopause-related diseases. While there is no question that HRT effectively mitigates troublesome menopause symptoms, conflicting evidence about other effects of HRT has fueled controversy concerning its relative benefits and risks. Moreover, it seems that CVD protection mediated by replacement therapy is maximum when treatment is initiated in the absence of signs of atherosclerosis (typically in the premenopausal period), whereas it vanishes as atherosclerosis progresses (postmenopausal period). However, many questions remain unsolved regarding the effectiveness of hormonal compounds, doses, regimens, and route of administration. On the basis of these considerations, it is necessary in the near future to expand scientific knowledge and develop appropriate lifestyle modifications and therapeutic strategies for the treatment of either traditional cardiovascular risk factors or menopause-related metabolic changes.

Hypertension is the most common chronic disease in industrialized countries and represents the most common major cardiovascular risk factor after the fifth decade of life in both men and women. The prevalence of hypertension is lower in premenopausal women than men, whereas in postmenopausal women it is higher than in men. Mechanisms responsible for the increase in blood pressure are complex and multifactorial, including loss of estrogen, oxidative stress, endothelial dysfunction, modification in renin-angiotensin system spillover and sympathetic activation. In addition, postmenopausal hypertension can be considered an isolated disease, more typical of elderly women, or part of the metabolic syndrome, which is indeed more common in early postmenopausal women. In particular, metabolic syndrome may be considered a potentially unfavourable prognostic factor in hypertensive postmenopausal women, because it seems to worsen the severity of hypertension and reduce the capacity to respond to specific treatments. This article summarizes the different causes of postmenopausal hypertension and the specific treatment recommended by guidelines for this condition.

More than a quarter of a million women die each year in the industrialized countries from cardiovascular diseases (CVD), and current projections indicate that this number will continue to rise with our ageing population. Important sex-related differences in the prevalence, presentation, management and outcomes of different CVD have discovered in the last two decades of cardiovascular research. Nevertheless, much evidence supporting contemporary recommendations for testing, prevention and treatment of CVD in women is still extrapolated from studies conducted predominantly in men. The compendium of CVD indicates that current research and strategy development must focus on gender-specific issues to address the societal burden and costs related to these incremental shifts in female gender involvement. Indeed, this significant burden of CVD in women places unique diagnostic, treatment and financial encumbrances on our society that are only further intensified by a lack of public awareness about the disease on the part of patients and clinicians alike. This societal burden of the disease is, in part, related to our poor understanding of gender-specific pathophysiologic differences in the presentation and prognosis of CVD and the paucity of diagnostic and treatment guidelines tailored to phenotypic differences in women. In this, scenario is of outmost importance to know these differences to provide the best care for female patients, because under-recognition of CVD in women may contribute to a worse clinical outcome. This review will provide a synopsis of available evidence on gender-based differences in the initial presentation, pathophysiology and clinical outcomes of women affected by CVD.

Background: The Mehran Risk Score (MRS) has been demonstrated to be clinically useful for prediction of contrast-induced nephropathy (CIN) after nonurgent percutaneous coronary intervention. We aim to validate the MRS in the setting of Primary percutaneous coronary intervention for prediction of both CIN and short- and long-term clinical outcomes., Methods and Results: We assigned 891 consecutive patients with ST-elevation-myocardial infarction undergoing primary percutaneous coronary intervention to 4 groups of risk of CIN (RC) according to MRS (low, medium, high, and very high risk). We evaluated CIN, death, and major cardiovascular and cerebrovascular events after 25 months' mean follow-up. At multivariable analysis, mortality in very high-risk group was more than 10-fold higher (hazard ratio [HR], 10.11; 95% confidence interval [CI], 4.83 to 21.1; P<0.001) when compared with the low-risk group and was also increased in the high-risk group (HR, 6.31; 95% CI, 3.28 to 12.14; P<0.001) and medium-risk group (HR, 3.18; 95% CI, 1.83 to 5.51; P<0.001). Similarly, an increasing effect was seen across MRS strata for major cardiovascular and cerebrovascular events both in the very high-risk group (HR, 3.79; 95% CI, 2.27 to 6.6.32; P<0.001), high-risk group (HR, 1.90; 95% CI, 1.31 to 2.75; P=0.001), and medium-risk group (HR, 1.42; 95% CI, 1.10 to 1.85; P=0.007). In addition, the HR for rehospitalization increased with the increasing RC groups (HR, 3.32; 95%CI, 1.96 to 5.63; P<0.001; HR, 3.11; 95% CI, 1.35 to 7.20; P=0.008; HR, 7.73; 95% CI, 2.97 to 20.10; P<0.001, respectively). The odds ratio for CIN was 2.84 (95% CI, 1.16 to 6.92; P=0.021) in the very high RC group, 1.33 (95% CI, 0.68 to 2.61; P=0.398) in the high RC group, and 1.10 (95% CI, 0.67 to 1.79; P=0.699) in the medium RC group, as compared with the lower one., Conclusions: The MRS may be applied in the primary angioplasty setting population and is able to predict CIN and to stratify patients for poor clinical outcomes both in the short- and long-term follow-up.

Recent advances in the field of cardiovascular medicine have not led to significant declines in case-fatality rates for women as in men. There are gender-specific differences in symptoms profile, diagnosis and treatment of coronary disease in women. For women presenting for coronary heart disease (CHD) evaluation, traditional disease management approaches that focus on detection of a 'critical stenosis' often fail to identify those women critically at-risk. Symptoms do not help physicians in differential diagnosis of chest pain in women; indeed the most common presentation of obstructive CHD in women is atypical symptoms. In 50% of the cases, non-obstructive CHD at coronary angiography, due to 'noncardiac chest pain' or coronary microvascular dysfunction is frequently reported. For these reasons, the evidence reviewed suggests that prognostic risk assessment may work relatively better than diagnostic obstructive coronary disease assessment for women., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: Few reports described outcomes of complete compared with infarct-related artery (IRA)-only revascularisation in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD). Moreover, no studies have compared the simultaneous treatment of non-IRA with the IRA treatment followed by an elective procedure for the other lesions (staged revascularisation)., Methods: The outcomes of 263 [corrected] consecutive patients with STEMI and multivessel CAD undergoing primary angioplasty were studied. Before the first angioplasty patients were randomly assigned to three different strategies: culprit vessel angioplasty-only (COR group); staged revascularisation (SR group) and simultaneous treatment of non-IRA (CR group)., Results: During a mean follow-up of 2.5 years, 42 (50.0%) patients in the COR group experienced at least one major adverse cardiac event (MACE), 13 (20.0%) in the SR group and 15 (23.1%) in the CR group, p<0.001. Inhospital death, repeat revascularisation and re-hospitalisation occurred more frequently in the COR group (all p<0.05), whereas there was no significant difference in re-infarction among the three groups. Survival free of MACE was significantly reduced in the COR group but was similar in the CR and SR groups., Conclusions: Culprit vessel-only angioplasty was associated with the highest rate of long-term MACE compared with multivessel treatment. Patients scheduled for staged revascularisation experienced a similar rate of MACE to patients undergoing complete simultaneous treatment of non-IRA.

Aims: To examine the independent prognostic role of functional mitral regurgitation (FMR) and its impact across the severity of chronic heart failure (CHF) in a large population of outpatients with systolic CHF followed at two multidisciplinary clinics., Methods and Results: Echocardiography was performed upon enrolment in 469 CHF patients. Follow-up for death and heart transplant was updated on January 2007. Five-year transplant-free survival was 82.7% in patients with no or Grade I FMR, 64.4% in Grade II, 58.5% in Grade III, and 46.5% in Grade IV (P < 0.0001). There was a strong graded association between FMR and the long-term risk of death and heart transplant, which remained significant after multivariable adjustment (P = 0.0003). The association between FMR and events was strong and independent in patients with less severe symptoms and in those at lower overall risk based on a propensity score analysis, while it was not significant in patients with more advanced CHF or in the high-risk subgroup (P < 0.0001 for interactions)., Conclusion: This study clarifies previous apparently discrepant results by demonstrating that FMR is an independent determinant of death and heart transplantation only in less severe CHF and in patients with a lower risk profile. This finding indicates that FMR plays a major role in the early phase of CHF, suggesting that this should be the focus of strategies attempting to reduce it.