Novelties in Therapy of Chronic Heart Failure.

In recent decades, considerable advances have been made in the treatment of heart failure. The main target of heart failure therapy is the inhibition of the sympathetic nervous system and renin-angiotensin-aldosterone system. The angiotensin receptor blockers represent a breakthrough in the treatment of heart failure with a demonstrated effect on reduction of cardiovascular events. However, new perspectives derive from latest drugs developed for diabetes, iron deficiency, and hyperkalemia. New frontiers are also opened to the development of neurohormonal therapies, antagonists of inflammatory mediators, inotropic agents, and cell-based treatments.

Tissue-tracking in the assessment of late gadolinium enhancement in myocarditis and myocardial infarction.

PURPOSE: To test the diagnostic performance of cardiovascular magnetic resonance (CMR) tissue-tracking (TT) to detect the presence of late gadolinium enhancement (LGE) in patients with a diagnosis of myocardial infarction (MI) or myocarditis (MYO), preserved left ventricular ejection fraction (LVEF) and no visual regional wall motion abnormalities (RWMA). METHODS: We selected consecutive CMR studies of 50 MI, 50 MYO and 96 controls. Receiving operating characteristic (ROC) curve and net reclassification index (NRI) analyses were used to assess the predictive ability and the incremental diagnostic yield of 2D and 3D TT-derived strain parameters for the detection of LGE and to measure the best cut-off values of strain parameters. RESULTS: Overall, cases showed significantly reduced 2D global longitudinal strain (2D-GLS) values compared with controls (-20.1 ± 3.1% vs -21.6 ± 2.7%; p = 0.0008). 2D-GLS was also significantly reduced in MYO patients compared with healthy controls (-19.7 ± 2.9% vs -21.9 ± 2.4%; p = 0.0001). 3D global radial strain (3D-GRS) was significantly reduced in MI patients compared with controls with risk factors (34.3 ± 11.8% vs 40.3 ± 12.5%, p = 0.024) Overall, 2D-GLS yielded good diagnostic accuracy for the detection of LGE in the MYO subgroup (AUROC 0.79; NRI (95% CI) = 0.6 (0.3, 1.02) p = 0.0004), with incremental predictive value beyond risk factors and LV function parameters (p for AUROC difference = 0.048). In the MI subgroup, 2D-GRS (AUROC 0.81; NRI (95% CI) = 0.56 (0.17, 0.95) p = 0.004), 3D-GRS (AUROC 0.82; NRI (95% CI) = 0.57 (0.17, 0.97) p = 0.006) and 3D global circumferential strain (3D-GCS) (AUROC 0.81; NRI (95% CI) = 0.62 (0.22, 1.01) p = 0.002) emerged as potential markers of disease. The best cut-off for 2D-GLS was -21.1%, for 2D- and 3D-GRS were 39.1% and 37.7%, respectively, and for 3D-GCS was -16.4%. CONCLUSIONS: At CMR-tissue tracking analysis, 2D-GLS was a significant predictor of LGE in patients with myocarditis but preserved LVEF and no visual RWMA. Both 2D- and 3D-GRS and 2D-GCS yielded good diagnostic accuracy for LGE detection in patients with previous MI but preserved LVEF and no visual RWMA.

Prognostic Significance of Left Ventricular Noncompaction: Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Although left ventricular noncompaction (LVNC) has been associated with an increased risk of adverse cardiovascular events, the accurate incidence of cardiovascular morbidity and mortality is unknown. We, therefore, aimed to assess the incidence rate of LVNC-related cardiovascular events. METHODS: We systematically searched observational studies reporting the adverse outcomes related to LVNC. The primary end point was cardiovascular mortality. RESULTS: We identified 28 eligible studies enrolling 2501 LVNC patients (mean age, 46 years; male/female ratio, 1.7). After a median follow-up of 2.9 years, the pooled event rate for cardiovascular mortality was 1.92 (95% CI, 1.54-2.30) per 100 person-years. LVNC patients had a similar risk of cardiovascular mortality compared with a dilated cardiomyopathy control group (odds ratio, 1.10 [95% CI, 0.18-6.67]). The incidence rates of all-cause mortality, stroke and systemic emboli, heart failure admission, cardiac transplantation, ventricular arrhythmias, and cardiac device implantation were 2.16, 1.54, 3.53, 1.24, 2.17, and 2.66, respectively, per 100 person-years. Meta-regression and subgroup analyses revealed that left ventricular ejection fraction, not the extent of left ventricular trabeculation, had an important influence on the variability of incidence rates. The risks of thromboembolism and ventricular arrhythmias in LVNC patients were similar to dilated cardiomyopathy patients. However, LVNC patients had a higher incidence of heart failure hospitalization than dilated cardiomyopathy patients. CONCLUSIONS: Patients with LVNC carry a similar cardiovascular risk when compared with dilated cardiomyopathy patients. Left ventricular ejection fraction-a conventional indicator of heart failure severity, not the extent of trabeculation-appears to be an important determinant of adverse outcomes in LVNC patients. Registration: https://www.crd.york.ac.uk/PROSPERO/ Unique identifier: CRD42018096313.

Pulmonary blood volume index as a quantitative biomarker of haemodynamic congestion in hypertrophic cardiomyopathy.

AIMS: The non-invasive assessment of left ventricular (LV) diastolic function and filling pressure in hypertrophic cardiomyopathy (HCM) is still an open issue. Pulmonary blood volume index (PBVI) by cardiovascular magnetic resonance (CMR) has been proposed as a quantitative biomarker of haemodynamic congestion. We aimed to assess the diagnostic accuracy of PBVI for left atrial pressure (LAP) estimation in patients with HCM. METHODS AND RESULTS: We retrospectively identified 69 consecutive HCM outpatients (age 58 ± 11 years; 83% men) who underwent both transthoracic echocardiography (TTE) and CMR. Guideline-based detection of LV diastolic dysfunction was assessed by TTE, blinded to CMR results. PBVI was calculated as the product of right ventricular stroke volume index and the number of cardiac cycles for a bolus of gadolinium to pass through the pulmonary circulation as assessed by first-pass perfusion imaging. Compared to patients with normal LAP, patients with increased LAP showed significantly larger PBVI (463 ± 127 vs. 310 ± 86 mL/m2, P < 0.001). PBVI increased progressively with worsening New York Heart Association functional class and echocardiographic stages of diastolic dysfunction (P < 0.001 for both). At the best cut-off point of 413 mL/m2, PBVI yielded good diagnostic accuracy for the diagnosis of LV diastolic dysfunction with increased LAP [C-statistic = 0.83; 95% confidence interval (CI): 0.73-0.94]. At multivariable logistic regression analysis, PBVI was an independent predictor of increased LAP (odds ratio per 10% increase: 1.97, 95% CI: 1.06-3.68; P = 0.03). CONCLUSION: PBVI is a promising CMR application for assessment of diastolic function and LAP in patients with HCM and may serve as a quantitative marker for detection, grading, and monitoring of haemodynamic congestion.

Prognostic Role of Left Ventricular Dysfunction in Patients With Coronary Artery Disease After an Ambulatory Cardiac Rehabilitation Program.

The relationship between left ventricular ejection fraction (LVEF) and outcomes after cardiac rehabilitation (CR) is not well established; therefore we assessed the prognostic role of LVEF at the end of ambulatory CR program in patients (pts) who received coronary revascularization. LVEF was evaluated at hospital discharge and re-assessed at the end of CR in all ST-elevation myocardial infarction and coronary artery bypass graft pts, while in pts with non-ST-elevation MI or elective percutaneous coronary intervention the echocardiography was repeated if they had an impaired LVEF at discharge. New hospitalizations for cardiovascular causes at 1-year, and cardiovascular mortality during long-term follow-up were analyzed. We enrolled in CR 3078 pts, 86% showed LVEF ≥40% and 9% LVEF <40%. Of those with a discharge LVEF <40%, 56% improved LVEF (LVEF ≥40%) after CR. At 1-year, heart failure was the main cause of new hospitalizations in LVEF <40% group compared with LVEF ≥40% group (5% vs 0.4%, p <0.01). During a mean follow up of 48 ± 25 months, cardiovascular death occurred in 9% of pts with LVEF <40% and in 2% with LVEF ≥40% (p = 0.014). At Cox multivariate analysis, LVEF <40% at the end of CR and age were independent predictors of hospitalization and mortality for cardiovascular causes, while coronary artery bypass graft was a protective factor. In conclusion, during CR the improvement of LVEF occurs in a relevant proportion of patients, the re-assessment of LVEF at the end of the CR is helpful for risk stratification because left ventricle dysfunction at the end of CR is associated with worse cardiovascular outcomes.

[The role of ambulatory cardiac rehabilitation on return to work of patients with cardiovascular diseases]. / Impatto della riabilitazione cardiaca ambulatoriale per la ripresa dell'attività lavorativa del cardiopatico.

SUMMARY: Cardiovascular diseases are the leading cause of morbidity and mortality in developed countries and about 50% of myocardial infarctions occur in working age individuals. Return to work rates are determined by cardiovascular parameters as well as by psychosocial factors and a Cardiac Rehabilitation program after an acute coronary syndrome or coronary revascularization has shown to improve the cardiovascular outcome, occupational recovery and professional reintegration through a multidisciplinary intervention including physical exercise, lipid and blood pressure control, smoking cessation program, nutritional advice, psychological counselling and target-driven pharmacological therapies. The collaboration between cardiologist and occupational physician is crucial in the transition from illness to an active social position defining the work eligibility with the assessment of cardiological profile, comorbidities, psychological functions, worker's ability and functional capacity.

Impact of ambulatory cardiac rehabilitation on cardiovascular outcomes: a long-term follow-up study.

AIMS: To evaluate the long-term clinical impact of the application of cardiac rehabilitation (CR) early after discharge in a real-world population. METHODS AND RESULTS: We analysed the 5-year incidence of cardiovascular mortality and hospitalization for cardiovascular causes in two populations, attenders vs. non-attenders to an ambulatory CR program which were consecutively discharged from two tertiary hospitals, after ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, coronary artery bypass graft, or planned percutaneous coronary intervention. A primary analysis using multivariable regression model and a secondary analysis using the propensity score approach were performed. Between 1 January 2009 and 31 December 2010, 839 patients attended a CR program planned at discharged, while 441 patients were discharged from Cardiovascular Department without any program of CR. During follow-up, the incidence of cardiovascular mortality was 6% in both groups (P = 0.62). The composite outcome of hospitalizations for cardiovascular causes and cardiovascular mortality were lower in CR group compared to no-CR group (18% vs. 30%, P < 0.001) and was driven by lower hospitalizations for cardiovascular causes (15 vs. 27%, P < 0.001). At multivariable Cox proportional hazard analysis, CR program was independent predictor of lower occurrence of the composite outcome (hazard ratio 0.58, 95% confidence interval 0.43-0.77; P < 0.001), while in the propensity-matched analysis CR group experienced also a lower total mortality (10% vs. 19%, P = 0.002) and cardiovascular mortality (2% vs. 7%, P = 0.008) compared to no-CR group. CONCLUSION: This study showed, in a real-world population, the positive effects of ambulatory CR program in improving clinical outcomes and highlights the importance of a spread use of CR in order to reduce cardiovascular hospitalizations and cardiovascular mortality during a long-term follow-up.

Are aortic coarctation and rheumatoid arthritis different models of aortic stiffness? Data from an echocardiographic study.

BACKGROUND: Patients who underwent a successful repair of the aortic coarctation (CoA) show high risk for cardiovascular (CV) events. Mechanical and structural abnormalities in the ascending aorta (Ao) might have a role in the prognosis of CoA patients. We analyzed the elastic properties of Ao measured as aortic stiffness index (AoSI) in CoA patients in the long-term period and we compared AoSI with a cohort of 38 patients with rheumatoid arthritis (RA) and 38 non-RA matched controls. METHODS: Data from 19 CoA patients were analyzed 28 ± 13 years after surgery. Abnormally high AoSI was diagnosed if AoSI > 6.07% (95th percentile of the AoSI detected in our reference healthy population). AoSI was assessed at the level of the aortic root by two-dimensional guided M-mode evaluation. RESULTS: CoA patients showed more than two-fold higher AoSI compared to RA and controls (9.8 ± 12.6 vs 4.8 ± 2.5% and 3.1 ± 2.0%, respectively; all p < 0.05 and in 5 of 19 patients with CoA (26%) AoSI was exceptionally high. The 5 patients with abnormally high AoSI were older with higher BP, LV mass and prevalence of LV diastolic dysfunction. Multiple linear regression analysis revealed that AoSI was independently related to the presence of LV hypertrophy and higher LV relative wall thickness. CONCLUSIONS: CoA patients have higher AoSI levels than RA patients and non-RA matched controls. AoSI levels are abnormally high in a small sub-group of CoA patients who show a very high-risk clinical profile for adverse CV events.

Early occurrence of drug intolerance as risk factor during follow-up in patients with acute coronary syndrome or coronary revascularization.

Aims: The occurrence of drug intolerance (DI) after an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) is an important reason for quitting treatment. Nevertheless, the association between DI and major cardiac and cerebrovascular events (MACCE) is poorly reported in the literature, therefore, we analysed potential relationship between DI and MACCE (a composite of ACS, PCI, heart failure, and stroke) during follow-up. Methods and results: From 1 January 2014 to 31 December 2015, 891 consecutive patients after ACS or coronary revascularization were referred to cardiac rehabilitation (CR) programme and included in a dedicated registry where DI was analysed and treatment appropriately tailored. Three hundred and nine patients (34.7%) developed DI, 26.9% of them were female. Angiotensin-converting enzyme (ACE) inhibitors and statins were the most frequent drugs which caused DI, followed by beta-blockers and calcium channel blockers, in 13.1%, 12.8%, 7.5%, and 5.5% of patients, respectively. During a median follow-up of 18 (interquartile range 11-24) months after CR, MACCE occurred in 14.1% of patients with DI and 8.1% without DI (P = 0.007). At multivariable model, DI to 1 drug [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.01-3.18; P = 0.043] or to 2 drugs (OR 2.56, 95% CI 1.27-5.17; P = 0.008) were independently associated to MACCE. Regarding the association of specific class of prognostic drugs to MACCE, only DI to ACE-inhibitors was independently associated with MACCE (OR 2.31, 95% CI 1.14-4.65; P = 0.019). Conclusion: DI was frequently encountered in real-world clinical practice and was significantly associated with MACCE during follow-up. This study suggests that early occurrence of DI could be considered to be an adjunctive cardiovascular risk factor during secondary prevention.

[Ambulatory cardiac rehabilitation in Trieste: protocols of intervention, activities and outcomes]. / Riabilitazione cardiologica ambulatoriale a Trieste: protocolli, attività ed esiti.

BACKGROUND: Cardiac rehabilitation (CR) is a model of care proven to reduce mortality and morbidity in patients with coronary artery disease. The aim of this study is to describe the ambulatory CR model of the Cardiovascular Department of Trieste (Italy), analyzing the outcome of the population. METHODS: We analyzed clinical and instrumental characteristics of all consecutive patients after ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), coronary artery bypass graft with or without valve surgery (CABG/CABGV), or planned percutaneous coronary intervention (PCI), referred for CR from January 1, 2009, to December 31, 2015. All patients were included in a registry. During CR and at 1-year follow-up, the incidence of new hospitalizations due to cardiovascular causes was assessed. Total and cardiovascular mortality was also evaluated at longer follow-up. RESULTS: Overall, 3088 patients (28% female, mean age 70 ± 11 years; 35% older than 75 years) were referred for CR, 30% after STEMI, 23% after NSTEMI, 29% after CABG/CABGV, and 19% after PCI. At enrollment, 9% of patients had an ejection fraction <40%, 76% were hypertensive, 61% dyslipidemic, 19% diabetics, and 27% smokers. CR lasted 5 ± 4 months. At the end of the CR program, 96% of patients were on antiplatelets, 79% on beta-blockers, 73% on angiotensin-converting enzyme inhibitors, 25% on angiotensin II receptor blockers, and 87% on statins with achievement of the following secondary prevention targets: LDL cholesterol 85 ± 30 mg/dl, glycated hemoglobin 7.2 ± 4%, heart rate 64 ± 11 bpm, systolic/diastolic blood pressure 137 ± 32/78 ± 14 mmHg. During CR, new hospitalizations occurred in 11% of patients, 1% within 1 year after CR. At a mean follow-up of 4.4 ± 2 years, 11% of patients died, 3% for cardiovascular causes, 0.7% within 1 year. Cardiovascular mortality was significantly higher in elderly patients (6 vs 2%, p=0.000), women (4 vs 3%, p=0.038), diabetics (5 vs 3%, p=0.004), and in patients with left ventricular dysfunction (8 vs 3%, p=0.000). CONCLUSIONS: Our findings show the feasibility of a CR program in an unselected population, characterized by advanced age, risk factors and comorbidities. A critical analysis of the registry data allowed us to achieve good results in secondary prevention and outcomes.

In Vivo Functional Selection Identifies Cardiotrophin-1 as a Cardiac Engraftment Factor for Mesenchymal Stromal Cells.

BACKGROUND: Transplantation of cells into the infarcted heart has significant potential to improve myocardial recovery; however, low efficacy of cell engraftment still limits therapeutic benefit. Here, we describe a method for the unbiased, in vivo selection of cytokines that improve mesenchymal stromal cell engraftment into the heart both in normal conditions and after myocardial infarction. METHODS: An arrayed library of 80 secreted factors, including most of the currently known interleukins and chemokines, were individually cloned into adeno-associated viral vectors. Pools from this library were then used for the batch transduction of bone marrow-derived mesenchymal stromal cells ex vivo, followed by intramyocardial cell administration in normal and infarcted mice. Three weeks after injection, vector genomes were recovered from the few persisting cells and identified by sequencing DNA barcodes uniquely labeling each of the tested cytokines. RESULTS: The most effective molecule identified by this competitive engraftment screening was cardiotrophin-1, a member of the interleukin-6 family. Intracardiac injection of mesenchymal stromal cells transiently preconditioned with cardiotrophin-1 preserved cardiac function and reduced infarct size, parallel to the persistence of the transplanted cells in the healing hearts for at least 2 months after injection. Engraftment of cardiotrophin-1-treated mesenchymal stromal cells was consequent to signal transducer and activator of transcription 3-mediated activation of the focal adhesion kinase and its associated focal adhesion complex and the consequent acquisition of adhesive properties by the cells. CONCLUSIONS: These results support the feasibility of selecting molecules in vivo for their functional properties with adeno-associated viral vector libraries and identify cardiotrophin-1 as a powerful cytokine promoting cell engraftment and thus improving cell therapy of the infarcted myocardium.

Acromegalic Cardiomyopathy With Malignant Arrhythmogenic Pattern Successfully Treated With Mechanical Circulatory Support and Heart Transplantation.

Cardiovascular involvement is common in acromegaly and can lead to development of acromegalic cardiomyopathy, characterized by concentric biventricular hypertrophy with a progressive impairment of diastolic and systolic function. The onset of heart failure and arrhythmias are related to poor prognosis. We report on a case of a 48-year-old man with acromegalic cardiomyopathy caused by pituitary adenoma. Despite the successful trans-sphenoidal resection of the tumour, the patient was rehospitalized for ventricular arrhythmic storms that led to cardiogenic shock, which required mechanical hemodynamic support with intra-aortic balloon pump, venoarterial extracorporeal membrane oxygenation, and urgent heart transplantation.

Cardiac imaging in patients with acute or chronic heart failure.

In recent years, imaging techniques have revolutionized the diagnosis of heart failure (HF) and they are indispensable for clinical decision-making in patients with acute and chronic HF. Echocardiography remains a first-line test in HF and continues to provide valuable information on left ventricular and valvular function. However, there is increasing evidence to integrate imaging modalities such as cardiovascular magnetic resonance, positron emission tomography and computed tomography, in the clinical care. In the future, a need on appropriate utilization of the different tools will raise and it will represent a challenge for cardiovascular specialists. Cardiologists and physicians will require an adequate training, knowing strengths and limitations of all these imaging techniques.

'PERFSCORE' - a multidimensional score: a simple way to predict the success of cardiac rehabilitation.

BACKGROUND: We propose a simple and reliable score, performance score ('PERFSCORE'), that allows cardiologists to assess the achievement of therapeutic goals. METHODS: We identified six indicators of cardiac rehabilitation performance: heart rate (HR) less than 70 beats/min; blood pressure (BP) less than 140/90 mmHg; smoking cessation or non-smokers; left ventricular ejection fraction (LVEF) more than 40%; LDLc less than 100 mg/dl or more than 70 mg/dl if diabetic; and on treatment at least with three drugs among angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARBs), ß-blockers, statins, and ASA. These six indicators are considered to be the collective expression of a latent variable measuring performance. To assess the relative contribution of each indicator in the definition of cardiac rehabilitation performance, we fitted a structural equation model using the 'Stata 13' system. RESULTS: A total of 839 consecutive patients were analyzed; 49% had recent ST- elevation myocardial infarction/non-ST elevation myocardial infarction and 51% had undergone elective percutaneous coronary intervention/coronary artery bypass graft. At the end of cardiac rehabilitation, LVEF was 55 ±â€Š11%; HR, 69 ±â€Š13 beats/min; SBP, 135 ±â€Š20 mmHg; DBP, 79 ±â€Š10 mmHg; LDLc, 88 ±â€Š29 mg/dl; 56% had stopped smoking; 71% were on ß-blockers; 78% ACE inhibitors or ARBs; 87% were on statins, and 96% were on ASA. Weights for each indicator in the PERFSCORE were 0.57 for HR, 0.40 for BP, 0.87 for LVEF, 0.78 for smoking, 0.42 for LDLc, and 0.75 for drugs, multiplied by 1 if the target has been reached, otherwise by 0. Higher performance values correspond to better cardiac rehabilitation results. The point range was 0-36: less than 24, not satisfying cardiac rehabilitation; 24-29, satisfying cardiac rehabilitation; and more than 29, optimal cardiac rehabilitation. CONCLUSION: In conclusion, we propose an easy algorithm to calculate the success of cardiac rehabilitation.

Long term survival in patients with cardiac amyloidosis. Prevalence and characterisation during follow-up.

BACKGROUND AND AIMS: Cardiac amyloidosis (CA) is usually characterised by a poor outcome in the short-term; clinical and instrumental features are heterogeneous and could characterise subgroups with different prognoses. The aim of our study was to describe a subgroup of patients with CA showing an impressive favourable long-term survival. METHODS: Out of 50 patients (males 65%, 63 ± 11 years) with an echocardiographic and bioptic diagnosis of CA observed from 1991 to 2009, we selected a subgroup of patients surviving more than 50 months from diagnosis (group 1). We described their features at enrolment and during follow-up, comparing them with patients surviving less than 12 months (group 2). RESULTS: We found seven patients (14%) belonging to group 1 and 26 (52%) to group 2. Four out of seven long term survivors suffered from AL amyloidosis, in one case the underlying aetiology was a chronic inflammatory disease, while in two cases remained unknown. At enrolment, group 1 patients showed higher systolic blood pressure with respect to group 2 (140 ± 25 vs. 112 ± 18 mmHg, respectively, p=0.011), and a less thick interventricular septum (IVS) (IVS thickness > 15 mm in 29% vs. 69% of patients, p = 0.049). No patient of group 1 presented left ventricular restrictive filling pattern (0 vs. 31% in group 1 and 2 respectively, p = 0.035), atrial fibrillation (0 vs. 35%, p = 0.024), or progression towards a more severe disease during follow-up. CONCLUSIONS: A not negligible proportion of patients with CA can have a long-term survival. They showed a less severe disease at diagnosis, with substantial stability over time. Further studies on larger populations are necessary to understand the mechanisms underlying this more favourable natural history of the disease.

Focus on cardiac amyloidosis: a single-center experience with a long-term follow-up.

AIM: Amyloidosis is a systemic disease, related to different underlying causes, with frequent cardiac involvement. Clinical evaluation, echocardiography and electrocardiography represent important noninvasive tools in identification of cardiac involvement. The aim of this study was to assess the clinical-laboratory features of a series of patients affected by cardiac amyloidosis in order to evaluate the risk of cardiac mortality. METHODS: We evaluated 48 patients (men 65%, mean age 63 ±â€Š11 years) with biopsy-proven diagnosis of amyloidosis and heart involvement observed from 1991 to 2009. All patients underwent clinical-laboratory evaluation at baseline and were followed up. RESULTS: During a median follow-up of 9.5 months (first to third interquartile: 3-41.5 months), 24 patients (50%) died as a result of a cardiac cause. Survival free from cardiac death was 69, 50, 48 and 41% at 6, 12, 24 and 60 months from diagnosis, respectively. At multivariable Cox regression analysis, the presence of heart failure at enrolment [hazard ratio (HR) 4.67, 95% confidence interval (CI) 1.07-20.27, P = 0.04] and history of recent syncope (HR 3.97, 95% CI 1.28-12.34, P = 0.017) emerged as independent predictors of cardiac death. By using the equation derived from the multivariate analysis, individual survival probability at different times of follow-up was calculated. CONCLUSION: We confirm the particularly poor outcome of cardiac amyloidosis in the short term. A careful clinical evaluation emerges as the most important tool for the prognostic stratification and quantification of risk in patients with cardiac amyloidosis.