Michele Senni - Academia.edu (original) (raw)

Papers by Michele Senni

Cardiac Failure Review

Sacubitril with valsartan (sacubitril/valsartan) is a relatively novel compound that has become a... more Sacubitril with valsartan (sacubitril/valsartan) is a relatively novel compound that has become a milestone in the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) in the last decade. Contemporary data suggest that sacubitril/valsartan is associated with improved outcomes compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and has a greater beneficial effect on myocardial reverse remodelling. Additionally, two recent trials have shown that sacubitril/valsartan is well-tolerated even in the acute HF setting, thus enabling a continuum of use in the patient’s journey with HFrEF. This article summarises available data on the effectiveness and tolerability of sacubitril/valsartan in patients with HFrEF, and provides the clinician with practical insights to facilitate the use of this drug in every setting, with an emphasis on acute HF, hypotension, electrolyte imbalance and renal insufficiency.

New England Journal of Medicine

Cardiogenetics

A 14-year-old boy with hypertrophic cardiomyopathy (HCM) diagnosed at the age of 1 year and with ... more A 14-year-old boy with hypertrophic cardiomyopathy (HCM) diagnosed at the age of 1 year and with massive left ventricular hypertrophy suffered an episode of ventricular fibrillation during mild effort. He underwent a dual-chamber implantable cardioverter defibrillator (ICD) implantation. The defibrillation threshold testing (DFT) was ineffective. Subcutaneous multi-coli arrays tunneled into the left postero-lateral position and connected to the superior vena cava (SVC) port of the dual-chamber ICD were added to increase the myocardial mass involved in the defibrillation shock pathway. A new DFT was unsuccessful. The patient was transferred to our hospital for myectomy. An epicardial defibrillation patch was placed on the left ventricular lateral wall, but again, DFT testing was ineffective using the right ventricular (RV) coil to lateral patch as shock pathway. Another epicardial defibrillation patch was then placed on the inferior wall. In this case, DFT testing was effective with ...

Circulation: Heart Failure

Background: The net clinical benefit of cardiac disease-modifying drugs might be influenced by th... more Background: The net clinical benefit of cardiac disease-modifying drugs might be influenced by the interaction of different domains of disease burden. We assessed the relative contribution of cardiac, comorbid, and demographic factors in heart failure (HF) and how their interplay might influence HF prognosis and efficacy of sacubitril/valsartan across the spectrum of left ventricular ejection fraction. Methods: We combined data from 2 global trials that evaluated the efficacy of sacubitril/valsartan compared with a renin-angiotensin antagonist in symptomatic HF patients (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure; n=8399] and PARAGON-HF [Prospective Comparison of Angiotensin-Converting Enzyme Inhibitor With Angiotensin Receptors Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction; n=4796]). We decomposed t...

Journal of Cardiovascular Computed Tomography

Journal of the American College of Cardiology

International Journal of Cardiology

BACKGROUND PARADIGM-HF demonstrated superiority of sacubitril/valsartan (sac/val) over enalapril ... more BACKGROUND PARADIGM-HF demonstrated superiority of sacubitril/valsartan (sac/val) over enalapril in patients with heart failure with reduced ejection fraction (HFrEF). However, patients in clinical practice may differ in their characteristics and overall risk compared with patients in clinical trials, and additional outcomes can be observed in real world (RW). Hence, a systematic review was conducted to identify and describe RW data on sac/val. METHODS RW studies evaluating the effects of sac/val in adult patients with HFrEF with a sample size ≥100 were identified via MEDLINE® and Embase® from 2015 to January 2020. Citations were screened, critically appraised and relevant data were extracted. RESULTS A total of 68 unique studies were identified. Nearly half of the studies were conducted in Europe (n = 34), followed by the US (n = 15) and Asia (n = 11). Median follow-up period varied from 1 to 19 months. Mean age ranged between 48.7 and 79.0 years; patients were mostly male and in New York Heart Association (NYHA) functional class II/III, and mean left ventricular ejection fraction varied between 23%and 38%. Of studies performing comparisons, most reported superior efficacy of sac/val in reducing the risk of HF hospitalisations, all-cause hospitalisations, and all-cause mortality as compared to standard-of-care. Many studies reported significant improvements in NYHA functional class and reduction in biomarker levels post sac/val. Hypotension and hyperkalaemia were the most frequently reported adverse events. CONCLUSIONS This comprehensive overview of currently available RW evidence on sac/val complements the evidence from randomised controlled trials, substantiating its effectiveness in heterogeneous real-world HF populations.

New England Journal of Medicine

BACKGROUND Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart... more BACKGROUND Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. METHODS In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. RESULTS Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin. CONCLUSIONS Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).

Structural Heart

ABSTRACT Transcatheter mitral valve intervention using the MitraClip system has evolved as a new ... more ABSTRACT Transcatheter mitral valve intervention using the MitraClip system has evolved as a new tool for the treatment of secondary mitral regurgitation (SMR) in patients with heart failure and reduced left ventricular ejection fraction (HFrEF). The purposes of this paper are, first, to review the pathophysiological mechanisms underlying the onset of SMR within the context of HFrEF progression; secondly, to reconcile the results from MitraClip randomized clinical trials and “real-world” registries, in order to highlight in a patient-based strategy the most relevant clinical predictors of favorable outcome after MitraClip implantation. The final goal is to identify the phenotype of the “ideal” patient and the most favorable timing for MitraClip treatment of SMR within the broad spectrum of HFrEF presentation.Guest Editor

Cardiovascular Ultrasound

Aims We sought to determine which echocardiographic markers of left ventricular (LV) remodeling a... more Aims We sought to determine which echocardiographic markers of left ventricular (LV) remodeling and diastolic dysfunction can contribute as incremental and independent prognostic information in addition to current clinical risk markers of ischemic LV systolic dysfunction in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Methods and results The cohort consisted of 1511 of 2136 patients in STICH for whom baseline transmitral Doppler (E/A ratio) could be measured by an echocardiographic core laboratory blinded to treatment and outcomes, and prognostic value of echocardiographic variables was determined by a Cox regression model. E/A ratio was the most significant predictor of mortality amongst diastolic variables with lowest mortality for E/A closest 0.8, although mortality was consistently low for E/A 0.6 to 1.0. Mortality increased for E/A 1.0 up to approximately 2.3, beyond which there was no further increase in risk. Larger LV end-systolic volume index (LVESVI) a...

Circulation

Introduction: Advanced heart failure (AdvHF) in HCM was overlooked. Hypothesis: Based on a system... more Introduction: Advanced heart failure (AdvHF) in HCM was overlooked. Hypothesis: Based on a systematic revision, we described prevalence & outcomes of the main HCM phenotypes responsible for AdvHF, heart transplantation (HTx), LVAD implantation & HF-death. Methods: We classified the HCM profiles responsible for AdvHF in 1) End-stage HCM (ES-HCM) defined by an LVEF≤50%; 2) LVOTO despite optimal medical therapy (OMT) (Refractory HOCM); 3) Nonobstructive HCM with preserved EF (HNOCMpEF). The study screened 130 manuscripts in MEDLINE and EMBASE on AdvHF in HCM patients (pts) published from 2000 till January 2020, in adults. 8 manuscripts were eligible for the analysis. AdvHF was defined by the presence of severe NYHA symptoms (III & IV) because in all the manuscripts this definition was used. Mean follow-up = 7.6 years. Results: Figure 1: Prevalence of phenotypes responsible for AdvHF&HTx/LVAD implantation/HF-Death. Of 205 HCM pts, 119 (58%) underwent HTx, LVAD implantation, or died for ...

European Heart Journal Supplements

Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) represent today... more Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) represent today the largest ‘unmet medical need’, because none of the drugs presently available improved survival in this consistent proportion of patients with HF, ∼50% of the total, who have an LV ejection fraction ≥50%. Heart failure with preserved left ventricular ejection fraction is a clinical syndrome that in its classical form, is associated to typical risk factors and comorbidities. The comorbidities represent one of the element contributing to the extreme heterogeneity which characterizes HFpEF. The pathophysiological mechanisms, as well as the clinical presentation, are multifaceted. These factors explain, by and large, the failure of a generalized therapeutic strategy, while build the argument for personalized medicine, designed to address the specific phenotypes, with therapies proven in specific subgroups of patients with HFpEF to reduce mortality and improve ‘surrogate’ outcomes, such as...

Cardiac Failure Review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COV... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has become a pandemic affecting every country in the world. In the province of Bergamo, Italy, more than 2,200 cases of COVID-19 have been reported, which include more than 300 deaths. Most hospitalisations have been at the Papa Giovanni XXIII Hospital. This has imposed a significant burden on our hospital in terms of healthcare personnel, dedicated spaces (including intensive care areas) and time spent by clinicians, who are committed to assisting COVID-19 patients. In this short expert opinion, the authors will focus on new insights related to COVID-19 and the cardiovascular system, and try to investigate the grey areas and uncertainties in this field.

European Journal of Heart Failure

Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose ... more Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose prevalence continues to rise, with high social and economic burden, but with no specific approved treatment. Patients diagnosed with HFpEF have a high prevalence of comorbidities and exhibit a high misdiagnosis rate. True HFpEF is likely to have multiple pathophysiological causes – with these causes being clinically ill‐defined due to limitations of current measurement techniques. Myocyte, interstitium, microvascular, and metabolic abnormalities have been regarded as key components of the pathophysiology and potential therapeutic targets. Cardiac magnetic resonance (CMR) has the capability to look deeper with a number of tissue characterization techniques which are closer to the underlying specific abnormalities and which could be linked to personalized medicine for HFpEF. This review aims to discuss the potential role of CMR to better define HFpEF phenotypes and to infer measurable therapeutic targets.

European Heart Journal

Bergamo is the town most affected by the COVID-19 epidemic, not only in the Lombardy Region but a... more Bergamo is the town most affected by the COVID-19 epidemic, not only in the Lombardy Region but also throughout Italy, with >9000 COVID-positive cases, and 2300 ascertained deaths. Unfortunately, the infection is not even sparing young people. The consequences of the COVID-19 emergency for the entire 'Papa Giovanni XXIII' Hospital of Bergamo have been dramatic. At present (mid-March), from a total of 779 hospital beds, >500 are occupied by COVID-positive patients. The 46 beds previously reserved for the ICU (intensive care unit) have been increased to 100, of which 88 are occupied by COVID-positive patients, all of them intubated and with an average age of 61 years. Due to the shortage of resources , a triage of the patients to be intubated was needed, based on data such as age, presence of comorbidity, degree of respiratory failure severity, and life expectancy. Although our hospital structure is at the forefront and with great flexibility for organization, during the last month it has run the risk of collapse, facing such a violent epidemic comparable to a tsunami, from which it differs in terms of time, lasting not a single day but more than a month. Clinicians are living in permanently stressful conditions, caused by concern for their own health and safety, severity of the infection, by seeing patients dying alone, and finally, by exhausting shifts and workload. Like many other colleagues (so far 12 out of 36 in our Cardiology Unit), I have contracted the infection at the hospital, and, as a consequence, I have been placed in isolation at home for about 2 weeks. This isolation has had personal effects, on family (my whole family was infected) and, not least, professional effects, since I was unable to manage 'on the spot' the other different Units of the Cardiovascular Department (Invasive Cardiology, Cardiac Surgery, and Vascular Surgery), except through video conferencing. My experience, similar to that of many other colleagues, teaches us, the physicians, how the hospitals can be the primary infection vehicle and that priority for the protection of medical staff must be given. To avoid them becoming an infection source, the medical staff must undergo swab tests at the onset of the first symptoms (even mild fever, sore throat, or cough) and all those who enter the hospital, i.e. patients, health staff, or others, must be supplied with and obliged to wear surgical masks. Our Cardiology Unit, as many other Units of the hospital, has had to face the need to change its own organization. At present, the Cardiology Unit has only 4 ICU beds and 40 ward beds (previously they were 8 and 50, respectively) 60% of which are occupied by COVID-19-positive patients. Non-urgent outpatient visits have been cancelled. However, particularly challenging is the management of patients listed for heart transplantation, LVAD patients, and heart transplant patients. The Cardiology Unit has become the hub for the cardiovascular emergencies of coronary revascularization and electrophysiology of Bergamo Province, which accounts for 1 150 000 people. We have modified the cardiology triage system to find functional and operative solutions to the increasing wave of patients arriving at the Emergency Department, and, at the same time, to manage the cardiological emergencies by limiting the infection risk. In detail, we have organized a fast track for patients arriving as emergencies from outside, avoiding the Emergency Department, reducing the infection risk, and allowing them to be directly managed by the cath. lab staff. Therefore, some possible suggestions that could help cardiologist colleagues to be prepared to start and face this health emergency are: (i) give priority to the protection of hospital health staff; (ii) provide adequate protective systems for the health staff and masks for hospitalized patients, outpatients, helpers, and visitors; (iii) adjust the hospital organization, with units dedicated to the treatment of COVID-positive patients, who should be separated from other patients; (v) change the triage for non-COVID patients; and (vi) use telemedicine or telephone Published on behalf of the European Society of Cardiology. All rights reserved.

Journal of the American College of Cardiology

European Journal of Preventive Cardiology

Background Natriuretic peptides and diastolic dysfunction have prognostic value in asymptomatic s... more Background Natriuretic peptides and diastolic dysfunction have prognostic value in asymptomatic subjects at risk for heart failure. Their integration might further refine the risk stratification process in this setting. Aim of this paper was to explore the possibility to predict heart failure and death combining diastolic dysfunction and natriuretic peptides in an asymptomatic population at risk for heart failure. Methods Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for heart failure. Baseline evaluation included electrocardiogram, echocardiogram, and natriuretic peptides collection. Based on diastolic dysfunction and natriuretic peptides, subjects were classified in four groups: control group (no diastolic dysfunction/normal natriuretic peptides, 57%), no diastolic dysfunction/high natriuretic peptides (9%), diastolic dysfunction/normal natriuretic pep...

European Heart Journal Supplements

The role of biomarkers is increasingly recognized in heart failure (HF) management, for diagnosis... more The role of biomarkers is increasingly recognized in heart failure (HF) management, for diagnosis, prognostication, and screening of high-risk patients. Beyond natriuretic peptides and troponins, the utility of novel, emerging biomarkers is less established. This document reflects the key points of a Heart Failure Association of the European Society of Cardiology (ESC) consensus meeting on biomarker monitoring in HF.

European Heart Journal - Cardiovascular Imaging

Aims Midwall fractional shortening (MWFS) is a measure of left ventricular (LV) systolic function... more Aims Midwall fractional shortening (MWFS) is a measure of left ventricular (LV) systolic function that is more reliable in case of concentric LV geometry compared to LV ejection fraction (LVEF). We hypothesized that MWFS might predict heart failure (HF) and death in a high-risk asymptomatic population, beyond other echocardiographic parameters. Methods and results Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in northern Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for HF. Baseline evaluation included clinical visit, electrocardiogram, N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiogram. Mean age of the population was 69 ± 7 years, 56% were men, 88% had hypertension, mean LVEF was 61 ± 9%, and mean MWFS 16.2 ± 3.3. During a median follow-up of 5.7 years, 95 subjects experienced HF/death events. At Cox analysis, lower MWFS was the only echocardiographic parameter, among structural/...

European Journal of Heart Failure

Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and ... more Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and reduced ejection fraction (HFrEF) in the ambulatory setting (PARADIGM‐HF), and following stabilisation of acutely decompensated HF (ADHF) (PIONEER‐HF and TRANSITION). However, data are lacking for the initiation of sacubitril/valsartan in newly diagnosed (de novo) HFrEF. Here, we assess the tolerability of initiating sacubitril/valsartan following ADHF in TRANSITION subgroups of patients with a de novo vs. prior diagnosis of HFrEF.

Cardiac Failure Review

Sacubitril with valsartan (sacubitril/valsartan) is a relatively novel compound that has become a... more Sacubitril with valsartan (sacubitril/valsartan) is a relatively novel compound that has become a milestone in the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) in the last decade. Contemporary data suggest that sacubitril/valsartan is associated with improved outcomes compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and has a greater beneficial effect on myocardial reverse remodelling. Additionally, two recent trials have shown that sacubitril/valsartan is well-tolerated even in the acute HF setting, thus enabling a continuum of use in the patient’s journey with HFrEF. This article summarises available data on the effectiveness and tolerability of sacubitril/valsartan in patients with HFrEF, and provides the clinician with practical insights to facilitate the use of this drug in every setting, with an emphasis on acute HF, hypotension, electrolyte imbalance and renal insufficiency.

New England Journal of Medicine

Cardiogenetics

A 14-year-old boy with hypertrophic cardiomyopathy (HCM) diagnosed at the age of 1 year and with ... more A 14-year-old boy with hypertrophic cardiomyopathy (HCM) diagnosed at the age of 1 year and with massive left ventricular hypertrophy suffered an episode of ventricular fibrillation during mild effort. He underwent a dual-chamber implantable cardioverter defibrillator (ICD) implantation. The defibrillation threshold testing (DFT) was ineffective. Subcutaneous multi-coli arrays tunneled into the left postero-lateral position and connected to the superior vena cava (SVC) port of the dual-chamber ICD were added to increase the myocardial mass involved in the defibrillation shock pathway. A new DFT was unsuccessful. The patient was transferred to our hospital for myectomy. An epicardial defibrillation patch was placed on the left ventricular lateral wall, but again, DFT testing was ineffective using the right ventricular (RV) coil to lateral patch as shock pathway. Another epicardial defibrillation patch was then placed on the inferior wall. In this case, DFT testing was effective with ...

Circulation: Heart Failure

Background: The net clinical benefit of cardiac disease-modifying drugs might be influenced by th... more Background: The net clinical benefit of cardiac disease-modifying drugs might be influenced by the interaction of different domains of disease burden. We assessed the relative contribution of cardiac, comorbid, and demographic factors in heart failure (HF) and how their interplay might influence HF prognosis and efficacy of sacubitril/valsartan across the spectrum of left ventricular ejection fraction. Methods: We combined data from 2 global trials that evaluated the efficacy of sacubitril/valsartan compared with a renin-angiotensin antagonist in symptomatic HF patients (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure; n=8399] and PARAGON-HF [Prospective Comparison of Angiotensin-Converting Enzyme Inhibitor With Angiotensin Receptors Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction; n=4796]). We decomposed t...

Journal of Cardiovascular Computed Tomography

Journal of the American College of Cardiology

International Journal of Cardiology

BACKGROUND PARADIGM-HF demonstrated superiority of sacubitril/valsartan (sac/val) over enalapril ... more BACKGROUND PARADIGM-HF demonstrated superiority of sacubitril/valsartan (sac/val) over enalapril in patients with heart failure with reduced ejection fraction (HFrEF). However, patients in clinical practice may differ in their characteristics and overall risk compared with patients in clinical trials, and additional outcomes can be observed in real world (RW). Hence, a systematic review was conducted to identify and describe RW data on sac/val. METHODS RW studies evaluating the effects of sac/val in adult patients with HFrEF with a sample size ≥100 were identified via MEDLINE® and Embase® from 2015 to January 2020. Citations were screened, critically appraised and relevant data were extracted. RESULTS A total of 68 unique studies were identified. Nearly half of the studies were conducted in Europe (n = 34), followed by the US (n = 15) and Asia (n = 11). Median follow-up period varied from 1 to 19 months. Mean age ranged between 48.7 and 79.0 years; patients were mostly male and in New York Heart Association (NYHA) functional class II/III, and mean left ventricular ejection fraction varied between 23%and 38%. Of studies performing comparisons, most reported superior efficacy of sac/val in reducing the risk of HF hospitalisations, all-cause hospitalisations, and all-cause mortality as compared to standard-of-care. Many studies reported significant improvements in NYHA functional class and reduction in biomarker levels post sac/val. Hypotension and hyperkalaemia were the most frequently reported adverse events. CONCLUSIONS This comprehensive overview of currently available RW evidence on sac/val complements the evidence from randomised controlled trials, substantiating its effectiveness in heterogeneous real-world HF populations.

New England Journal of Medicine

BACKGROUND Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart... more BACKGROUND Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. METHODS In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. RESULTS Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin. CONCLUSIONS Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).

Structural Heart

ABSTRACT Transcatheter mitral valve intervention using the MitraClip system has evolved as a new ... more ABSTRACT Transcatheter mitral valve intervention using the MitraClip system has evolved as a new tool for the treatment of secondary mitral regurgitation (SMR) in patients with heart failure and reduced left ventricular ejection fraction (HFrEF). The purposes of this paper are, first, to review the pathophysiological mechanisms underlying the onset of SMR within the context of HFrEF progression; secondly, to reconcile the results from MitraClip randomized clinical trials and “real-world” registries, in order to highlight in a patient-based strategy the most relevant clinical predictors of favorable outcome after MitraClip implantation. The final goal is to identify the phenotype of the “ideal” patient and the most favorable timing for MitraClip treatment of SMR within the broad spectrum of HFrEF presentation.Guest Editor

Cardiovascular Ultrasound

Aims We sought to determine which echocardiographic markers of left ventricular (LV) remodeling a... more Aims We sought to determine which echocardiographic markers of left ventricular (LV) remodeling and diastolic dysfunction can contribute as incremental and independent prognostic information in addition to current clinical risk markers of ischemic LV systolic dysfunction in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Methods and results The cohort consisted of 1511 of 2136 patients in STICH for whom baseline transmitral Doppler (E/A ratio) could be measured by an echocardiographic core laboratory blinded to treatment and outcomes, and prognostic value of echocardiographic variables was determined by a Cox regression model. E/A ratio was the most significant predictor of mortality amongst diastolic variables with lowest mortality for E/A closest 0.8, although mortality was consistently low for E/A 0.6 to 1.0. Mortality increased for E/A 1.0 up to approximately 2.3, beyond which there was no further increase in risk. Larger LV end-systolic volume index (LVESVI) a...

Circulation

Introduction: Advanced heart failure (AdvHF) in HCM was overlooked. Hypothesis: Based on a system... more Introduction: Advanced heart failure (AdvHF) in HCM was overlooked. Hypothesis: Based on a systematic revision, we described prevalence & outcomes of the main HCM phenotypes responsible for AdvHF, heart transplantation (HTx), LVAD implantation & HF-death. Methods: We classified the HCM profiles responsible for AdvHF in 1) End-stage HCM (ES-HCM) defined by an LVEF≤50%; 2) LVOTO despite optimal medical therapy (OMT) (Refractory HOCM); 3) Nonobstructive HCM with preserved EF (HNOCMpEF). The study screened 130 manuscripts in MEDLINE and EMBASE on AdvHF in HCM patients (pts) published from 2000 till January 2020, in adults. 8 manuscripts were eligible for the analysis. AdvHF was defined by the presence of severe NYHA symptoms (III & IV) because in all the manuscripts this definition was used. Mean follow-up = 7.6 years. Results: Figure 1: Prevalence of phenotypes responsible for AdvHF&HTx/LVAD implantation/HF-Death. Of 205 HCM pts, 119 (58%) underwent HTx, LVAD implantation, or died for ...

European Heart Journal Supplements

Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) represent today... more Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) represent today the largest ‘unmet medical need’, because none of the drugs presently available improved survival in this consistent proportion of patients with HF, ∼50% of the total, who have an LV ejection fraction ≥50%. Heart failure with preserved left ventricular ejection fraction is a clinical syndrome that in its classical form, is associated to typical risk factors and comorbidities. The comorbidities represent one of the element contributing to the extreme heterogeneity which characterizes HFpEF. The pathophysiological mechanisms, as well as the clinical presentation, are multifaceted. These factors explain, by and large, the failure of a generalized therapeutic strategy, while build the argument for personalized medicine, designed to address the specific phenotypes, with therapies proven in specific subgroups of patients with HFpEF to reduce mortality and improve ‘surrogate’ outcomes, such as...

Cardiac Failure Review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COV... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has become a pandemic affecting every country in the world. In the province of Bergamo, Italy, more than 2,200 cases of COVID-19 have been reported, which include more than 300 deaths. Most hospitalisations have been at the Papa Giovanni XXIII Hospital. This has imposed a significant burden on our hospital in terms of healthcare personnel, dedicated spaces (including intensive care areas) and time spent by clinicians, who are committed to assisting COVID-19 patients. In this short expert opinion, the authors will focus on new insights related to COVID-19 and the cardiovascular system, and try to investigate the grey areas and uncertainties in this field.

European Journal of Heart Failure

Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose ... more Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose prevalence continues to rise, with high social and economic burden, but with no specific approved treatment. Patients diagnosed with HFpEF have a high prevalence of comorbidities and exhibit a high misdiagnosis rate. True HFpEF is likely to have multiple pathophysiological causes – with these causes being clinically ill‐defined due to limitations of current measurement techniques. Myocyte, interstitium, microvascular, and metabolic abnormalities have been regarded as key components of the pathophysiology and potential therapeutic targets. Cardiac magnetic resonance (CMR) has the capability to look deeper with a number of tissue characterization techniques which are closer to the underlying specific abnormalities and which could be linked to personalized medicine for HFpEF. This review aims to discuss the potential role of CMR to better define HFpEF phenotypes and to infer measurable therapeutic targets.

European Heart Journal

Bergamo is the town most affected by the COVID-19 epidemic, not only in the Lombardy Region but a... more Bergamo is the town most affected by the COVID-19 epidemic, not only in the Lombardy Region but also throughout Italy, with >9000 COVID-positive cases, and 2300 ascertained deaths. Unfortunately, the infection is not even sparing young people. The consequences of the COVID-19 emergency for the entire 'Papa Giovanni XXIII' Hospital of Bergamo have been dramatic. At present (mid-March), from a total of 779 hospital beds, >500 are occupied by COVID-positive patients. The 46 beds previously reserved for the ICU (intensive care unit) have been increased to 100, of which 88 are occupied by COVID-positive patients, all of them intubated and with an average age of 61 years. Due to the shortage of resources , a triage of the patients to be intubated was needed, based on data such as age, presence of comorbidity, degree of respiratory failure severity, and life expectancy. Although our hospital structure is at the forefront and with great flexibility for organization, during the last month it has run the risk of collapse, facing such a violent epidemic comparable to a tsunami, from which it differs in terms of time, lasting not a single day but more than a month. Clinicians are living in permanently stressful conditions, caused by concern for their own health and safety, severity of the infection, by seeing patients dying alone, and finally, by exhausting shifts and workload. Like many other colleagues (so far 12 out of 36 in our Cardiology Unit), I have contracted the infection at the hospital, and, as a consequence, I have been placed in isolation at home for about 2 weeks. This isolation has had personal effects, on family (my whole family was infected) and, not least, professional effects, since I was unable to manage 'on the spot' the other different Units of the Cardiovascular Department (Invasive Cardiology, Cardiac Surgery, and Vascular Surgery), except through video conferencing. My experience, similar to that of many other colleagues, teaches us, the physicians, how the hospitals can be the primary infection vehicle and that priority for the protection of medical staff must be given. To avoid them becoming an infection source, the medical staff must undergo swab tests at the onset of the first symptoms (even mild fever, sore throat, or cough) and all those who enter the hospital, i.e. patients, health staff, or others, must be supplied with and obliged to wear surgical masks. Our Cardiology Unit, as many other Units of the hospital, has had to face the need to change its own organization. At present, the Cardiology Unit has only 4 ICU beds and 40 ward beds (previously they were 8 and 50, respectively) 60% of which are occupied by COVID-19-positive patients. Non-urgent outpatient visits have been cancelled. However, particularly challenging is the management of patients listed for heart transplantation, LVAD patients, and heart transplant patients. The Cardiology Unit has become the hub for the cardiovascular emergencies of coronary revascularization and electrophysiology of Bergamo Province, which accounts for 1 150 000 people. We have modified the cardiology triage system to find functional and operative solutions to the increasing wave of patients arriving at the Emergency Department, and, at the same time, to manage the cardiological emergencies by limiting the infection risk. In detail, we have organized a fast track for patients arriving as emergencies from outside, avoiding the Emergency Department, reducing the infection risk, and allowing them to be directly managed by the cath. lab staff. Therefore, some possible suggestions that could help cardiologist colleagues to be prepared to start and face this health emergency are: (i) give priority to the protection of hospital health staff; (ii) provide adequate protective systems for the health staff and masks for hospitalized patients, outpatients, helpers, and visitors; (iii) adjust the hospital organization, with units dedicated to the treatment of COVID-positive patients, who should be separated from other patients; (v) change the triage for non-COVID patients; and (vi) use telemedicine or telephone Published on behalf of the European Society of Cardiology. All rights reserved.

Journal of the American College of Cardiology

European Journal of Preventive Cardiology

Background Natriuretic peptides and diastolic dysfunction have prognostic value in asymptomatic s... more Background Natriuretic peptides and diastolic dysfunction have prognostic value in asymptomatic subjects at risk for heart failure. Their integration might further refine the risk stratification process in this setting. Aim of this paper was to explore the possibility to predict heart failure and death combining diastolic dysfunction and natriuretic peptides in an asymptomatic population at risk for heart failure. Methods Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for heart failure. Baseline evaluation included electrocardiogram, echocardiogram, and natriuretic peptides collection. Based on diastolic dysfunction and natriuretic peptides, subjects were classified in four groups: control group (no diastolic dysfunction/normal natriuretic peptides, 57%), no diastolic dysfunction/high natriuretic peptides (9%), diastolic dysfunction/normal natriuretic pep...

European Heart Journal Supplements

The role of biomarkers is increasingly recognized in heart failure (HF) management, for diagnosis... more The role of biomarkers is increasingly recognized in heart failure (HF) management, for diagnosis, prognostication, and screening of high-risk patients. Beyond natriuretic peptides and troponins, the utility of novel, emerging biomarkers is less established. This document reflects the key points of a Heart Failure Association of the European Society of Cardiology (ESC) consensus meeting on biomarker monitoring in HF.

European Heart Journal - Cardiovascular Imaging

Aims Midwall fractional shortening (MWFS) is a measure of left ventricular (LV) systolic function... more Aims Midwall fractional shortening (MWFS) is a measure of left ventricular (LV) systolic function that is more reliable in case of concentric LV geometry compared to LV ejection fraction (LVEF). We hypothesized that MWFS might predict heart failure (HF) and death in a high-risk asymptomatic population, beyond other echocardiographic parameters. Methods and results Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in northern Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for HF. Baseline evaluation included clinical visit, electrocardiogram, N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiogram. Mean age of the population was 69 ± 7 years, 56% were men, 88% had hypertension, mean LVEF was 61 ± 9%, and mean MWFS 16.2 ± 3.3. During a median follow-up of 5.7 years, 95 subjects experienced HF/death events. At Cox analysis, lower MWFS was the only echocardiographic parameter, among structural/...

European Journal of Heart Failure

Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and ... more Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and reduced ejection fraction (HFrEF) in the ambulatory setting (PARADIGM‐HF), and following stabilisation of acutely decompensated HF (ADHF) (PIONEER‐HF and TRANSITION). However, data are lacking for the initiation of sacubitril/valsartan in newly diagnosed (de novo) HFrEF. Here, we assess the tolerability of initiating sacubitril/valsartan following ADHF in TRANSITION subgroups of patients with a de novo vs. prior diagnosis of HFrEF.