Bioprosthetic pulmonary valve dysfunction in a primary cardiac sarcoma survivor: Clinical considerations and treatment options.

The case highlights the good survival after radical surgery and chemotherapy of a cardiac sarcoma, and the need for close follow-up due to possible early postsurgical complications.

2-year outcomes of MitraClip as a bridge to heart transplantation: The international MitraBridge registry.

BACKGROUND: In the first report from the MitraBridge registry, MitraClip as a bridge to heart transplantation (HTx) proved to be at 1-year an effective treatment strategy for 119 patients with advanced heart failure (HF) who were potential candidates for HTx. We aimed to determine if benefits of MitraClip procedure as a bridge-to-transplant persist up to 2-years. METHODS: By the end of the enrollment period, a total of 153 advanced HF patients (median age 59 years, left ventricular ejection fraction 26.9 ± 7.7%) with significant secondary mitral regurgitation, who were potential candidates for HTx and were treated with MitraClip as a bridge-to-transplant strategy, were included in the MitraBridge registry. The primary endpoint was the 2-year composite adverse events rate of all-cause death, first hospitalization for HF, urgent HTx or LVAD implantation. RESULTS: Procedural success was achieved in 89.5% of cases. Thirty-day mortality was 0%. At 2-year, Kaplan-Meier estimates of freedom from primary endpoint was 47%. Through 24 months, the annualized rate of HF rehospitalization per patient-year was 44%. After an overall median follow-up time of 26 (9-52) months, elective HTx was successfully performed in 30 cases (21%), 19 patients (13.5%) maintained or obtained the eligibility for transplant, and 32 patients (22.5%) no longer had an indication for HTx because of significant clinical improvement. CONCLUSIONS: After 2-years of follow-up, the use of MitraClip as a bridge-to-transplant was confirmed as an effective strategy, allowing elective HTx or eligibility for transplant in one third of patients, and no more need for transplantation in 22.5% of cases.

How Coronary Perforation Looks at Optical Coherence Tomography Imaging.

In this case, review of OCT images after successful closure of a coronary perforation (CP) showed that the initial CP was visible as an abrupt interruption of the intimal tissue and the presence of a crater with blood reaching the external layers of vessel wall. CP was probably caused by overstretch of the vessel wall in an intramural segment of the left anterior descending coronary artery. CP is a possible complication of PTCA that is rarely documented with intracoronary imaging due to its rapid and dramatic evolution. We report the unique images of how an initial CP appears at OCT.

Impact of hemoglobin levels at admission on outcomes among elderly patients with acute coronary syndrome treated with low-dose Prasugrel or clopidogrel: A sub-study of the ELDERLY ACS 2 trial.

Hemoglobin (Hb) levels have emerged as a useful tool for risk stratification and the prediction of outcome after myocardial infarction. We aimed at evaluating the prognostic impact of this parameter among patients in advanced age, where the larger prevalence of anemia and the higher rate of comorbidities could directly impact on the cardiovascular risk. METHODS: All the patients in the ELDERLY-2 trial, were included in this analysis and stratified according to the values of hemoglobin at admission. The primary endpoint of this study was cardiovascular mortality within one year. The secondary endpoints were all-cause mortality, MI, Bleeding Academic Research Consortium (BARC) type 2-3 or 5 bleeding, any stroke, re-hospitalization for cardiovascular event or stent thrombosis (probable or definite) within 12 months after index admission. RESULTS: We included in our analysis 1364 patients, divided in quartiles of Hb values (<12.2; 12.2-13.39; 13.44-14.49; ≥ 4.5 g/dl). At a mean follow- up of 330.4 ± 99.9 days cardiovascular mortality was increased in patients with lower Hb (HR[95%CI] = 0.76 [0.59-0.97], p = 0.03). Results were no more significant after correction for baseline differences (adjusted HR[95%CI] = 1.22 [0.41-3.6], p = 0.16). Similar results were observed for overall mortality. At subgroup analysis, (according to Hb median values) a significant interaction was observed only with the type of antiplatelet therapy, but not with major high-risk subsets of patients. CONCLUSIONS: Among elderly patients with acute coronary syndrome managed invasively, lower hemoglobin at admission is associated with higher cardiovascular and all-cause mortality and major ischemic events, mainly explained by the higher risk profile.

Lyme Carditis: From Pathophysiology to Clinical Management.

Cardiac involvement is a rare but relevant manifestation of Lyme disease that frequently presents as atrioventricular block (AVB). Immune-mediated injury has been implicated in the pathogenesis of Lyme carditis due to possible cross-reaction between Borrelia burgdorferi antigens and cardiac epitopes. The degree of the AVB can fluctuate rapidly, with two-thirds of patients progressing to complete AVB. Thus, continuous heart rhythm monitoring is essential, and a temporary pacemaker may be necessary. Routinely permanent pacemaker implantation, however, is contraindicated because of the frequent transient nature of the condition. Antibiotic therapy should be initiated as soon as the clinical suspicion of Lyme carditis arises to reduce the duration of the disease and minimize the risk of complications. Diagnosis is challenging and is based on geographical epidemiology, clinical history, signs and symptoms, serological testing, ECG and echocardiographic findings, and exclusion of other pathologies. This paper aims to explain the pathophysiological basis of Lyme carditis, describe its clinical features, and delineate the treatment principles.

Global longitudinal strain by CMR improves prognostic stratification in acute myocarditis presenting with normal LVEF.

BACKGROUND: Prognostic stratification of acute myocarditis (AM) presenting with normal left ventricular ejection fraction (LVEF) relies mostly on late gadolinium enhancement (LGE) characterization. Left ventricular peak global longitudinal strain (LV-GLS) measured by feature tracking analysis might improve prognostication of AM presenting with normal LVEF. METHODS: Data of patients undergoing cardiac magnetic resonance (CMR) for clinically suspected AM in seven European Centres (2013-2020) were retrospectively analysed. Patients with AM confirmed by CMR and LVEF ≥50% were included. LGE was visually characterized: localized versus. non-localized, subepicardial versus midwall. LV-GLS was measured by dedicated software. The primary outcome was the first occurrence of an adverse cardiovascular event (ACE) including cardiac death, life-threatening arrhythmias, development of heart failure or of LVEF <50%. RESULTS: Of 389 screened patients, 256 (66%) fulfilled inclusion criteria: median age 36 years, 71% males, median LVEF 60%, median LV-GLS -17.3%. CMR was performed at 4 days from hospitalization. At 27 months, 24 (9%) patients experienced ≥1 ACE (71% developed LVEF <50%). Compared to the others, they had lower median LV-GLS values (-13.9% vs. -17.5%, p = .001). At Kaplan-Meier analysis, impaired LV-GLS (both considered as > -20% or quartiles), non-localized and midwall LGE were associated with ACEs. Patients with LV-GLS ≤-20% did not experience ACEs. LV-GLS remained associated with ACEs after adjustment for non-localized and midwall LGE. CONCLUSION: In AM presenting with LVEF ≥50%, LV-GLS provides independent prognostic value over LGE characterization, improving risk stratification and representing a rationale for further studies of therapy in this cohort.

Effect of prehospital treatment in STEMI patients undergoing primary PCI.

BACKGROUND: The appropriate timing to administer antithrombotic therapies in ST-elevation myocardial infarction (STEMI) remains uncertain. This study aims to evaluate the role of antithrombotic therapy administration at first medical contact (FMC) compared with the administration in the Cathlab. METHODS: We conducted a "before-after" observational study enrolling STEMI undergoing primary percutaneous coronary intervention (PCI). Outcomes were evaluated during two successive periods, before (control group: aspirin only at FMC) and after (pretreated intervention group: heparin, aspirin plus ticagrelor at FMC) the introduction of a new regional pretreatment protocol. RESULTS: A total of 537 consecutive patients (300 in control vs. 237 in intervention group) were enrolled. The pretreated compared with no pretreated population showed better basal reperfusion, expressed as basal Thrombolysis in Myocardial Infarction (TIMI)-flow (p for trend p < 0.001). Pretreated population showed lower frequency of TIMI 0 (56.5% vs. 73.7%, odds ratio [OR]: 0.46, 95% confidence interval [CI]: 0.32-0.67, p < 0.001) and higher frequency of TIMI 2-3 (33.3% vs. 19.3% OR: 2.0, 95% CI: 1.38-2.00, p < 0.001) and TIMI 3 (14.3% vs. 9.7%, OR: 1.56, 95% CI: (0.92-2.65), p = 0.094). Pretreated compared with no pretreated population showed reduced infarct size expressed as Troponin Peak (20,286 (8726-75,027) versus 48,676 (17,229-113,900), p = 0.001), and higher left ventricular ejection fraction at discharge (53% (44-59) vs. 50% (44-56), p = 0.027). In-hospital BARC ≥ 2 bleeding were similar (2.1% vs. 2.0%, p = 0.929, in pretreated versus no pretreated population, respectively). CONCLUSION: This study provides support for an early pretreatment strategy in STEMI patients and confirmed the importance of an efficient organization of STEMI networks which allow initiation of antithrombotic treatment at FMC.

Arrhythmic risk stratification by cardiac magnetic resonance tissue characterization: disclosing the arrhythmic substrate within the heart muscle.

Sudden cardiac death (SCD) is a pivotal health problem worldwide. The identification of subjects at increased risk of SCD is crucial for the accurate selection of candidates for implantable cardioverter defibrillator (ICD) therapy. Current strategies for arrhythmic stratification largely rely on left ventricular (LV) ejection fraction (EF), mostly measured by echocardiography, and New York Heart Association functional status for heart failure with reduced EF. For specific diseases, such as hypertrophic and arrhythmogenic cardiomyopathy, some risk scores have been proposed; however, these scores take into account some parameters that are a partial reflection of the global arrhythmic risk and show a suboptimal accuracy. Thanks to a more comprehensive evaluation, cardiac magnetic resonance (CMR) provides insights into the heart muscle (the so-called tissue characterization) identifying cardiac fibrosis as an arrhythmic substrate. Combining sequences before and after administration of contrast media and mapping techniques, CMR is able to characterize the myocardial tissue composition, shedding light on both intracellular and extracellular alterations. Over time, late gadolinium enhancement (LGE) emerged as solid prognostic marker, strongly associated with major arrhythmic events regardless of LVEF, adding incremental value over current strategy in ischemic heart disease and non-ischemic cardiomyopathies. The evidence on a potential prognostic role of mapping imaging is promising. However, mapping techniques require further investigation and standardization. Disclosing the arrhythmic substrate within the myocardium, CMR should be considered as part of a multiparametric approach to personalized arrhythmic stratification.

Early prognostic stratification and identification of irreversibly shocked patients despite primary percutaneous coronary intervention.

BACKGROUND: Despite prognostic improvements in ST-elevation myocardial infarction (STEMI), patients presenting with cardiogenic shock (CS) have still high mortality. Which are the relevant early prognostic factors despite revascularization in this high-risk population is poorly investigated. METHODS: We analyzed STEMI patients treated with primary percutaneous coronary intervention (PCI) and enrolled at the University Hospital of Trieste between 2012 and 2018. A decision tree based on data available at first medical contact (FMC) was built to stratify patients for 30-day mortality. Multivariate analysis was used to explore independent factors associated with 30-day mortality. RESULTS: Among 1222 STEMI patients consecutively enrolled, 7.5% presented with CS. CS compared with no-CS patients had worse 30-day mortality (33% vs 3%, P < 0.01). Considering data available at FMC, CS patients with a combination of age ≥76 years, anterior STEMI and an expected ischemia time > 3 h and 21 min were at the highest mortality risk, with a 30-day mortality of 85.7%. In CS, age (OR 1.246; 95% CI 1.045-1,141; P = 0.003), final TIMI flow 2-3 (OR 0.058; 95% CI 0.004-0.785; P = 0.032) and Ischemia Time (OR = 1.269; 95% CI 1.001-1.609; P = 0.049) were independently associated with 30-day mortality. CONCLUSIONS: In a contemporary real-world population presenting with CS due to STEMI, age is a relevant negative factor whereas an early and successful PCI is positively correlated with survival. However, a subgroup of elderly patients had severe prognosis despite revascularization. Whether pPCI may have an impact on survival in a very limited number of irreversibly critically ill patients remains uncertain and the identification of irreversibly shocked patients remains nowadays challenging.

Prognostic Significance of Feature-Tracking Right Ventricular Global Longitudinal Strain in Non-ischemic Dilated Cardiomyopathy.

Aims: Left ventricular global longitudinal strain (GLS) by cardiac magnetic resonance feature tracking (CMR-FT) analysis has shown an incremental prognostic value compared to classical parameters in non-ischemic dilated cardiomyopathy (NICM). However, less is known about the role of right ventricular (RV) GLS. Our objective was to evaluate the prognostic impact of RV-GLS by CMR-FT analysis in a population of NICM patients. Methods: In this multicenter study, we examined NICM patients evaluated with a comprehensive CMR-FT study. Major cardiac events (MACEs) were considered as the study primary outcome measure and were defined as a composite of (a) cardiovascular death, (b) cardiac transplant or destination therapy ventricular assist device, (c) hospitalization for life-threatening ventricular arrhythmias or implantable cardiac defibrillator appropriate intervention. Heart failure (HF) related events, including hospitalizations and life-threatening arrhythmia-related events were considered as secondary end-points. Receiver operating time-dependent analysis were used to calculate the possible additional effect of RV-GLS to standard evaluation. Results: We consecutively enrolled 273 patients. During a median follow-up of 39 months, 41 patients (15%) experienced MACEs. RV-GLS and LV late gadolinium emerged as the strongest prognostic CMR-FT variables: their association provided an estimated 3-year MACEs rate of 29%. The addition of RV-GLS significantly improved the prognostic accuracy in predicting MACEs with respect to the standard evaluation including LGE (areas under the curve from 0.71 [0.66-0.82] to 0.76 [0.66-0.86], p = 0.03). On competing risk analysis, RV-GLS showed a significant ability to reclassify overall both HF-related and life-threatening arrhythmia-related events, regardless of LV and RV ejection fraction. Conclusions: In NICM patients, RV-GLS showed a significant prognostic role in reclassifying the risk of MACEs, incremental with respect to standard evaluation with standard prognostic parameters.

Clinical impact of myocardial fibrosis in severe aortic stenosis.

The pressure overload due to the progressive narrowing of the valve area determines the development of the left ventricular hypertrophy which characterizes aortic stenosis (AS). The onset of myocardial fibrosis marks the inexorable decline of an initially compensatory response towards heart failure. However, myocardial fibrosis does not yet represent a key element in the prognostic and therapeutic framework of AS. In this context, cardiac magnetic resonance imaging plays a major role by highlighting both the focal irreversible fibrotic replacement, using the late gadolinium enhancement (LGE) technique, and the earlier diffuse reversible interstitial fibrosis, using the T1 mapping techniques. For this reason, the presence of myocardial fibrosis would be useful to identify a subgroup of patients at greater risk of events among the subjects with severe AS. Actually, more and more evidences seem to identify the presence of LGE as a powerful prognostic factor to be used to optimize the timing of prosthetic valve replacement. Randomized clinical trials, such as the EVoLVeD trial currently underway, will be needed to better define the importance of myocardial fibrosis assessment in the management of patients with AS.

STEMI and Multivessel Disease: Medical Therapy Amplifies the Benefit of Complete Myocardial Revascularisation.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) with multivessel disease (MVD) may be treated with different revascularisation strategies. However, the potential predictors of outcomes on top of different revascularisation strategies are poorly studied. This study aimed to evaluate the prognostic impact of two different revascularisation strategies and the potential impact of medical therapy. METHODS: Using a propensity score approach, the impact of two treatment strategies was analysed -staged non-culprit revascularisation group vs culprit-lesion-only percutaneous coronary intervention (PCI) group -- on a composite outcome of cardiovascular death (CVD), myocardial infarction, and repeated revascularisation. Moreover, models were further adjusted for medication at discharge. RESULTS: Among 1,385 STEMI patients treated with primary PCI, a subgroup of 433 with MVD was analysed. At the median follow-up of 41 (IQR, 21-65) months, after propensity-score adjustment, the multivariable Cox proportional hazard analysis showed that the staged non-culprit revascularisation group was associated with a lower composite endpoint (HR, 0.44; 95% CI, 0.24-0.82; p=0.01), lower CVD (HR, 0.34; 95% CI, 0.14-0.82; p=0.02), and lower all-cause death (HR, 0.46; 95% CI, 0.24-0.86; p=0.02). Use of renin-angiotensin inhibitors was associated with lower CVD (HR, 0.51; 95% CI, 0.27-0.95; p=0.03), and both renin-angiotensin inhibitors (HR, 0.52; 95% CI, 0.32-0.86; p=0.01) and beta blockers (HR, 0.48; 95% CI, 0.29-0.79; p=0.01) were associated with lower all-cause death. CONCLUSIONS: In a real-word STEMI population with multivessel disease, staged non-culprit revascularisation was associated with lower cardiovascular mortality compared with a culprit-only PCI strategy. However, both revascularisation and medical therapy played a role in the improvement of mortality outcomes. Medical therapy amplified the benefit of myocardial revascularisation.

The alcohol-induced cardiomyopathy: A cardiovascular magnetic resonance characterization.

BACKGROUND: Alcoholic cardiomyopathy(ACM) is part of the non-ischaemic dilated cardiomyopathy(NI-DCM) spectrum. Little is known about cardiovascular magnetic resonance(CMR) features in ACM patients. The aim of this study is to describe CMR findings and their prognostic impact in ACM patients. METHODS: Consecutive ACM patients evaluated in five referral CMR centres from January 2005 to December 2018 were enrolled. CMR findings and their prognostic value were compared to idiopathic NI-DCM(iNI-DCM) patients. The main outcome was a composite of death/heart transplantation/life-threatening arrhythmias. RESULTS: Overall 114 patients (52 with ACM and 62 with iNI-DCM) were included. ACM patients were more often males compared to iNI-DCM (90% vs 64%, respectively, p ≤ 0.001) and were characterized by a more pronounced biventricular adverse remodelling than iNI-DCM, i.e. lower LVEF (31 ± 12% vs 38 ± 11% respectively, p = 0.001) and larger left ventricular end-diastolic volume (116 ± 40 ml/m2 vs 67 ± 20 ml/m2 respectively, p < 0.001). Similarly to iNI-DCM, late gadolinium enhancement (LGE), mainly midwall, was present in more than 40% of ACM patients but, conversely, it was not associated with adverse outcome(p = 0.15). LGE localization was prevalently septal (87%) in ACM vs lateral in iNI-DCM(p < 0.05). Over a median follow-up of 42 months [Interquartile Range 24-68], adverse outcomes were similar in both groups(p = 0.67). CONCLUSIONS: ACM represents a specific phenotype of NI-DCM, with severe morpho-functional features at the onset, but similar long-term outcomes compared to iNI-DCM. Despite the presence and pattern of distribution of LGE was comparable, ACM and iNI-DCM showed a different LGE localization, mostly septal in ACM and lateral in iNI-DCM, with different prognostic impact.

COVID-19 impact on ST-elevation myocardial infarction incidence rate in a Italian STEMI network: a U-shaped curve phenomenon.

BACKGROUND: Public health emergencies such as the COVID-19 outbreak may impact on the incidence rate of ST-elevation myocardial infarction (STEMI) in severely affected areas. However, this phenomenon demands attention also in areas where media and patients were focused on the COVID-19 pandemic, but the healthcare system was not overwhelmed by the huge number of COVID-19 patients. METHODS AND RESULTS: In this observational study, we compared the incidence rate of all consecutive STEMI patients admitted at the University Hospital of Trieste, Italy, during March and April 2020 with the same 2 months of the previous 5 years (2015-2019). Patient characteristics were compared between 2020 and 2019.The incidence rate of STEMI admission in March-April 2020 was lower than those in March-April 2015-2019, 36 vs. 56 cases per 100 000 inhabitants/year [relative risk (RR) 0.65, 95% confidence interval (95% CI) 0.42-0.96, P = 0.045]. Considering that the incidence rates were constant in the past years (P = 0.24), the turnaround in 2020 is most likely due to the COVID-19 outbreak. Interestingly, this reduction was a dynamic phenomenon with a U-shaped curve during the 2-month period. System-of-care times were similar between 2020 and 2019; however in 2020, patients presented more frequently signs of heart failure compared to 2019 (Killip class ≥2 in 68% vs. 29%, P = 0.003). CONCLUSION: During the COVID-19 outbreak, we observed a marked reduction in the STEMI incidence rate. This U-shaped phenomenon demands attention because a potential cause for the decrease in STEMI incidence may include the avoidance of medical care. Public campaigns aiming to increase awareness of ischemic symptoms may be needed during community outbreak.

Focus on arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy is a myocardial disease generally caused by desmosomal mutations and characterized by progressive replacement of cardiomyocites with fibro-adipose tissue. In the classic form of the disease right ventricle is predominantly affected. However, biventricular and left-dominant variants have been recently recognized, leading to the new nosological definition of arrhythmogenic cardiomyopathy. The condition affects mostly young adults and athletes and is clinically characterized by ventricular arrhythmias, heart failure and sudden cardiac death. The diagnosis is based on clinical-instrumental criteria, including family history, morpho-functional and electrocardiographic abnormalities, ventricular arrhythmias and genetic defects (Task Force Criteria, 2010). The main goal in the management of patients is the prevention of sudden cardiac death, where implantable cardioverter-defibrillator is the only effective therapeutic strategy. Many arrhythmic risk factors have been described. Recently, an on-line calculator has been proposed, but it needs further validation.

[Diagnostic work-up and clinical management of cardiomyopathies: the operative protocol from the Cardiothoracovascular Department of Trieste, Italy]. / Inquadramento e gestione delle cardiomiopatie: il protocollo della Cardiologia di Trieste.

Cardiomyopathies are primary myocardial disorders, genetically determined, with clinical onset between the third and the fifth decade of life. They represent the main causes of sudden cardiac death and heart failure in the youth. The more common myocardial diseases in clinical practice are dilated cardiomyopathy, arrhythmogenic cardiomyopathy and hypertrophic cardiomyopathy. Next generation sequencing techniques, recently available for genetics researches, together with the diffusion of advanced imaging techniques, permitted in the last years a deeper knowledge of these pathologies. Nevertheless, diagnosis, etiology and several aspects of patients' clinical management remain complex and controversial. This review paper aims to propose some operative flow-charts, derived from scientific evidences and the internal protocol of the Cardiothoracovascular Department of Trieste Hospital, Italian referral Center for cardiomyopathies and heart failure, with more than 30 years of experience in diagnosis and management of patients who suffer from primary myocardial disorders.

MitraClip in secondary mitral regurgitation as a bridge to heart transplantation: 1-year outcomes from the International MitraBridge Registry.

BACKGROUND: Patients awaiting heart transplantation (HTx) often need bridging therapies to reduce worsening and progression of underlying disease. Limited data are available regarding the use of the MitraClip procedure in secondary mitral regurgitation for this clinical condition. METHODS: We evaluated an international, multicenter (17 centers) registry including 119 patients (median age: 58 years) with moderate-to-severe or severe secondary mitral regurgitation and advanced heart failure (HF) (median left ventricular ejection fraction: 26%) treated with MitraClip as a bridge strategy according to 1 of the following criteria: (1) patients active on HTx list (in list group) (n = 31); (2) patients suitable for HTx but awaiting clinical decision (bridge to decision group) (n = 54); or (3) patients not yet suitable for HTx because of potentially reversible relative contraindications (bridge to candidacy group) (n = 34). RESULTS: Procedural success was achieved in 87.5% of cases, and 30-day survival was 100%. At 1 year, Kaplan-Meier estimates of freedom from the composite primary end-point (death, urgent HTx or left ventricular assist device implantation, first rehospitalization for HF) was 64%. At the time of last available follow-up (median: 532 days), 15% of patients underwent elective transplant, 15.5% remained or could be included in the HTx waiting list, and 23.5% had no more indication to HTx because of clinical improvement. CONCLUSIONS: MitraClip procedure as a bridge strategy to HTx in patients with advanced HF with significant mitral regurgitation was safe, and two thirds of patients remained free from adverse events at 1 year. These findings should be considered exploratory and hypothesis-generating to guide further study for percutaneous intervention in high-risk patients with advanced HF.

Modifications of medical treatment and outcome after percutaneous correction of secondary mitral regurgitation.

AIMS: The optimization of guideline-directed medical therapy (GDMT) in reduced ejection fraction heart failure (HFrEF) is associated with improved survival and can reduce the severity of secondary mitral regurgitation (SMR). Highest tolerated doses should be achieved before percutaneous mitral valve repair (pMVR) and drugs titration further pursued after procedure. The degree of GDMT titration in patients with HFrEF and SMR treated with pMVR remains unexplored. We sought to evaluate the adherence to GDMT in HFrEF in patients undergoing pMVR and to explore the association between changes in GDMT post-pMVR and prognosis. METHODS AND RESULTS: We included all the patients with HFrEF and SMR ≥ 3 + treated with pMVR between 2012 and 2019 and with available follow-up. GDMT, comprehensive of dosages, was systematically recorded. The study endpoint was a composite of death and heart transplantation. Among 133 patients successfully treated, 121 were included (67 ± 12 years old, 77% male patients). Treatment rates of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitor (ACEIs/ARBs/ARNI), beta-blockers, and mineralcorticoid receptor antagonist at baseline and follow-up were 73% and 79%, 85% and 84%, 70% and 70%, respectively. At baseline, 33% and 32% of patients were using >50% of the target dose of ACEI/ARB/ARNI and beta-blockers. At follow-up (median time 4 months), 33% of patients unchanged, 34% uptitrated, and 33% of patients downtitrated GDMT. Downtitration of GDMT was independently associated with higher risk of death/heart transplantation (hazard ratio: 2.542, 95%confidence interval: 1.377-4.694, P = 0.003). CONCLUSIONS: Guideline-directed medical therapy is frequently underdosed in HFrEF patients with SMR undergoing pMVR. Downtitration of medications after procedure is associated with poor prognosis.

Impact of diabetes on clinical outcome among elderly patients with acute coronary syndrome treated with percutaneous coronary intervention: insights from the ELDERLY ACS 2 trial.

BACKGROUND: Despite recent improvements in percutaneous coronary revascularization and antithrombotic therapies for the treatment of acute coronary syndromes, the outcome is still unsatisfactory in high-risk patients, such as the elderly and patients with diabetes. The aim of the current study was to investigate the prognostic impact of diabetes on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study carried out at 32 centers in Italy. METHODS: Our population is represented by 1443 patients included in the Elderly-ACS 2 trial. Diabetes was defined as known history of diabetes at admission. The primary endpoint of this analysis was cardiovascular mortality, while secondary endpoints were all-cause death, recurrent myocardial infarction, Bleeding Academic Research Consortium type 2 or 3 bleeding, and rehospitalization for cardiovascular event or stent thrombosis within 12 months after index admission. RESULTS: Diabetes was present in 419 (29%) out of 1443 patients. Diabetic status was significantly associated with major cardiovascular risk factors and history of previous coronary disease, presentation with non-ST segment elevation myocardial infarction (P = 0.01) more extensive coronary disease (P = 0.02), more advanced Killip class at presentation (P = 0.003), use at admission of statins (P = 0.004) and diuretics at discharge (P < 0.001). Median follow-up was 367 days (interquartile range: 337-378 days). Diabetic status was associated with an absolute increase in the rate of cardiovascular mortality as compared with patients without diabetes [5.5 vs. 3.3%, hazard ratio (HR) 1.7 (0.99-2.8), P = 0.054], particularly among those treated with clopidogrel [HR (95% confidence interval (CI)) = 1.89 (0.93-3.87), P = 0.08]. However, this difference disappeared after correction for baseline differences [Adjusted HR (95% CI) 1.1(0.4-2.9), P = 0.86]. Similar findings were observed for other secondary endpoints, except for bleeding complications, significantly more frequent in diabetic patients [HR (95% CI) 2.02 (1.14-3.6), P = 0.02; adjusted HR (95% CI) = 2.1 (1.01-4.3), P = 0.05]. No significant interaction was observed between type of dual antiplatelet therapy, diabetic status and outcome. CONCLUSION: Among elderly patients with acute coronary syndromes, diabetic status was associated with higher rates of comorbidities, more severe cardiovascular risk profile and major bleeding complications fully accounting for the absolute increase in mortality. In fact, diabetes mellitus did not emerge as an independent predictor of survival in advanced age.