Metabolic Syndrome and Heart Transplantation: An Underestimated Risk Factor?

Metabolic Syndrome (MetS), a multifactorial condition that increases the risk of cardio-vascular events, is frequent in Heart-transplant (HTx) candidates and worsens with immunosuppressive therapy. The aim of the study was to analyze the impact of MetS on long-term outcome of HTx patients. Since 2007, 349 HTx patients were enrolled. MetS was diagnosed if patients met revised NCEP-ATP III criteria before HTx, at 1, 5 and 10 years of follow-up. MetS was present in 35% of patients pre-HTx and 47% at 1 year follow-up. Five-year survival in patients with both pre-HTx (65% vs. 78%, p < 0.01) and 1 year follow-up MetS (78% vs 89%, p < 0.01) was worst. At the univariate analysis, risk factors for mortality were pre-HTx MetS (HR 1.86, p < 0.01), hypertension (HR 2.46, p < 0.01), hypertriglyceridemia (HR 1.50, p=0.03), chronic renal failure (HR 2.95, p < 0.01), MetS and diabetes at 1 year follow-up (HR 2.00, p < 0.01; HR 2.02, p < 0.01, respectively). MetS at 1 year follow-up determined a higher risk to develop Coronary allograft vasculopathy at 5 and 10 year follow-up (25% vs 14% and 44% vs 25%, p < 0.01). MetS is an important risk factor for both mortality and morbidity post-HTx, suggesting the need for a strict monitoring of metabolic disorders with a careful nutritional follow-up in HTx patients.

Italian Association of Hospital Cardiologists Position Paper 'Gender discrepancy: time to implement gender-based clinical management'.

It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases.

Influence of donor-transmitted coronary artery disease on long-term outcomes after heart transplantation - a retrospective study.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is an important cause of late mortality after heart transplantation, which may be influenced by preexisting coronary disease (CAD) in the donor heart. METHODS: The aim of this study was to verify whether CAD in the donor heart had any influence on survival, cardiac-related adverse events (CRAEs), and coronary disease progression after transplantation. Donor coronary angiography performed in 289 hearts showed absence of CAD in 232 (no-CAD group) and moderate (≤50%) stenoses (CAD group) in 57. The 2 groups were compared for survival, freedom from CRAEs, and development of grade ≥ 2 CAV after transplantation. RESULTS: Of 30-day mortality and postoperative complication rate was similar as mean follow-up (76 ± 56 and 75 ± 55 months) for no-CAD and CAD (P = 0.8). Ten-year actuarial survival was 58 ± 4% and 62 ± 7% for no-CAD and CAD (P = 0.4). Ten-year freedom from grade ≥ 2 CAV and from CRAEs was 81 ± 4% and 66 ± 5% vs 75 ± 8% and 67 ± 9% in no-CAD and CAD (P = 0.9 and 0.9, respectively). CONCLUSIONS: Donor hearts with moderate CAD did not affect survival, freedom from CRAEs and did not accelerate development of high-grade CAV after transplantation supporting the use of such grafts to expand the donor pool. Routine use of coronary angiography in donor selection appears justified.

Role of Cardiac Rehabilitation After Ventricular Assist Device Implantation.

Patients with heart failure suffered by a complex syndrome, where the filling of the ventricle or ejection of the blood is impaired. In this setting, the exercise capacity decreases for many reasons, one of them being the insufficient oxygen transfer due to reduced cardiac output and anemia. Ventricular assist device has emerged as a durable and safe therapy for patients with end-stage heart failure. The benefits of cardiac rehabilitation in ventricular assist device patients are enormous: the first aim is to progressively reduce the physical and functional impairments of these patients, so that they will be able to resume meaningful daily activities.

An Integrated Approach for Treatment of Acute Type A Aortic Dissection.

Background and objective: We reviewed a single-institution experience to verify the impact of surgery during different time intervals on early and late results in the treatment of patients with type A acute aortic dissection (A-AAD). Materials and Methods: From 2004 to 2021, a total of 258 patients underwent repair of A-AAD; patients were equally distributed among three periods: 2004-2010 (Era 1, n = 90), 2011-2016 (Era 2, n = 87), and 2017-2021 (Era 3, n = 81). The primary end-point was to assess whether through the years changes in indications, surgical strategies and techniques and increasing experience have influenced early and late outcomes of A-AAD repair. Results: Axillary artery cannulation was almost routinely used in Eras 2 (86%) and 3 (91%) while one femoral artery was mainly cannulated in Era 1 (91%) (p < 0.01). Retrograde cerebral perfusion was predominantly used in Era 1 (60%) while antegrade cerebral perfusion was preferred in Eras 2 (94%,) and 3 (100%); (p < 0.01). There was a significant increase of arch replacement procedures from Era 1 (11%) to Eras 2 (33%) and 3 (48%) (p < 0.01). A frozen elephant trunk was mainly performed in Era 3. Hospital mortality was 13% in Era 1, 11% in Era 2, and 4% in Era 3 (p = 0.07). Actuarial survival at 3 years is 74%, in Era 1, 78% in Era 2, and 89% in Era 3 (p = 0.05). Conclusions: With increasing experience and a more aggressive approach, including total arch replacement, repair of A-AAD can be performed with low operative mortality in many patients. Patient care and treatment by a specific team organization allows a faster diagnosis and referral for surgery allowing to further improve early and late outcomes.

Donor-recipient age interaction and the impact on clinical results after heart transplantation.

To evaluate the impact of donor-recipient age matching on clinical outcomes after heart transplantation, a total of 509 patients (January 1990-December 2018, mean follow-up 111 ± 80 months) were stratified into 4 groups (young-R/young-D, young-R/old-D, old-R/young-D, old-R/old-D) according to the recipient (young-R < 60, old-R ≥ 60 years) and the donor (young-D < 50, old-D ≥ 50 years) age. No difference was found among 30-day mortality (P = .11) and postoperative complications between groups. Both unadjusted and adjusted survival was significantly higher for group young-R/young-D than that of other groups, in which survival was similar [adjusted HR for mortality of 2.0(1.2-3.4), 2.1(1.4-3.8) and 2.5(1.6-4.1) for groups old-R/young-D, young-R/old-D, old-R/old-D, respectively]. Compared to other groups, the incidence of grade ≥ 2 CAV was significantly lower in old-R/young-D group [adjusted HR 0.4(0.2-0.7)]. Among young recipients, the rate of acute grade ≥ 2 rejection episodes was higher in those receiving an old donor graft (P = .04). Old recipient groups were more affected by neoplasms and severe renal failure than young recipient groups (P < .01). Employment of hearts from donors ≥50 years of age adversely affects survival in recipients <60 years of age but does not influence outcomes in older recipients. Also, donor and recipient ages seem to have opposite effects on incidence of rejections and CAV of high grade.

Heart transplantation in cardiac storage diseases: data on Fabry disease and cardiac amyloidosis.

PURPOSE OF REVIEW: To deeply investigate one type of intracellular cardiac storage disease, the Fabry disease and one example of extracellular cardiac storage disease, the cardiac amyloidosis, with the aim to collect data about cardiac treatment at the end-stage level and the feasibility of heart transplantation (HTx) in this setting of patients. RECENT FINDINGS: Some registry describes that Fabry disease and cardiac amyloidosis showed similar characteristics as hypertrophic cardiomyopathies; thus, their correct diagnosis is often missing or time consuming. A multiorgan approach is mandatory to recognize the main systemic findings of these diseases, involving also the kidneys, the brain, the autonomous system and the skin. SUMMARY: The early diagnosis of these diseases is required to start as soon as possible the correct therapy for the patients affected. However, the end-stage heart failure is common and HTx could be offered to selected patients, especially if affected by light chain cardiac amyloidosis, to allow to perform the autologous stem cell transplantation after the cardiac transplant. Considering the Fabry disease patients, the enzyme recombinant therapy is also mandatory after HTx to avoid potential release of the systemic disease on the donor graft.

Arrhythmogenic right ventricular cardiomyopathy or athlete's heart? Challenges in assessment of right heart morphology and function.

The incidence of sudden cardiac death (SCD) in young athletes varies among studies, due to the disagreement in the definitions and the lack of information in this field.

Effect of uric acid serum levels on carotid arterial stiffness and intima-media thickness: A high resolution Echo-Tracking Study.

Serum uric acid (UA) has been shown to be a predictor of cardiovascular (CV) morbidity and mortality, and it may play a role in the pathogenesis of CV disease affecting vascular structure and function. However, there is limited evidence of its specific association with carotid artery stiffness and structure. The aim of our study was to evaluate whether UA is associated with early signs of atherosclerosis, namely local carotid arterial stiffness and intima-media thickening. We evaluated 698 consecutive asymptomatic patients, referred to the Cardiovascular Department for risk factors evaluation and treatment. All patients underwent carotid artery ultrasonography with measurement of common carotid intima-media thickness (IMT) and echo-tracking carotid artery stiffness index Beta. Patients with hyperuricemia (defined as serum uric acid ≥7 mg/dL in men and ≥6 mg/dL in women) had higher IMT (0.97±0.22 vs 0.91±0.18, p<0.001) and stiffness index Beta (8.3±3.2 vs 7.5±2.7, p=0.005). UA levels correlated with both IMT (r=0.225; p<0.001) and stiffness index Beta (r=0.154; p<0.001); the correlations were statistically significant in males and females. In a multivariate model which included age, arterial pressure, serum glucose and LDL-cholesterol, serum UA emerged as an independent explanatory variable of IMT and stiffness index Beta. Carotid IMT and local arterial stiffness are related to UA independently of established CV risk factors; UA may play a role in the early development of atherosclerosis.

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.

Value of ejection fraction/velocity ratio in the prognostic stratification of patients with asymptomatic aortic valve stenosis.

BACKGROUND: The ejection fraction/velocity ratio (EFVR) is a simple function-corrected index of aortic stenosis severity with a good correlation with aortic valve area measured using the Gorlin formula at cardiac catheterization. It is calculated by dividing left ventricular ejection fraction (LVEF) to 4 × (peak jet velocity)2 . OBJECTIVE: Our aim was to evaluate the value of EFVR in predicting adverse events in patients with asymptomatic aortic stenosis. METHODS: We analyzed the clinical and echocardiographic data of 216 asymptomatic patients with at least moderate aortic stenosis (AVA ≤ 1.5 cm2 ). The primary end-point was cardiovascular death or aortic valve replacement. RESULTS: There were 119 (55%) men and mean age was 68 ± 10 years. The mean follow-up time was 4.2 ± 1.6 years (median 4.3 years). During follow-up, the composite end-point of death or aortic valve replacement was reached in 105 patients (49%). Using multivariate Cox regression analysis, EFVR and valvulo-arterial impedance emerged as independent variables associated with outcome (P < 0.001 and P = 0.001, respectively). In the subgroup of patients with severe aortic stenosis (AVA < 1 cm2 ), EFVR ≤ 0.9 was associated with an increased hazard ratio for the composite end-point of mortality and aortic valve replacement (HR 2.14, 95% CI: 1.15-4.0, P = 0.017), even after adjusting for aortic valve area. CONCLUSIONS: In patients with asymptomatic moderate to severe aortic stenosis, EFVR is useful for risk stratification. Our results suggest that incorporating EFVR in the evaluation of patients with asymptomatic aortic stenosis might help identify those who are most likely to benefit from early elective aortic replacement.

New classification of geometric ventricular patterns in severe aortic stenosis: Could it be clinically useful?

BACKGROUND: In severe aortic stenosis, different left ventricle (LV) remodeling patterns as a response to pressure overload have distinct hemodynamic profiles, cardiac function, and outcomes. The most common classification considers LV relative wall thickness and LV mass index to create 4 different groups. A new classification including also end-diastolic volume index has been recently proposed. AIM: To describe the prevalence of the newly identified remodeling patterns in patients with severe aortic stenosis and to evaluate their clinical relevance according to symptoms. METHODS: We analyzed 286 consecutive patients with isolated severe aortic stenosis. Current guidelines were used for echocardiographic evaluation. Symptoms were defined as the presence of angina, syncope, or NYHA class III-IV. RESULTS: The mean age was 75 ± 9 years, 156 patients (54%) were men, while 158 (55%) were symptomatic. According to the new classification, the most frequent remodeling pattern was concentric hypertrophy (57.3%), followed by mixed (18.9%) and dilated hypertrophy (8.4%). There were no patients with eccentric remodeling; only 4 patients had a normalLV geometry. Symptomatic patients showed significantly more mixed hypertrophy (P < .05), while the difference regarding the prevalence of the other patterns was not statistically significant. When we analyzed the distribution of the classic 4 patterns stratified by the presence of symptoms, however, we did not find a significant difference (P = .157). CONCLUSIONS: The new classification had refined the description of different cardiac geometric phenotypes that develop as a response to pressure overload. It might be superior to the classic 4 patterns in terms of association with symptoms.

Anderson-Fabry Disease: Red Flags for Early Diagnosis of Cardiac Involvement.

Anderson-Fabry disease (AFD) is a lysosome storage disorder resulting from an X-linked inheritance of a mutation in the galactosidase A (GLA) gene encoding for the enzyme alpha-galactosidase A (α-GAL A). This mutation results in a deficiency or absence of α-GAL A activity, with a progressive intracellular deposition of glycosphingolipids leading to organ dysfunction and failure. Cardiac damage starts early in life, often occurring sub-clinically before overt cardiac symptoms. Left ventricular hypertrophy represents a common cardiac manifestation, albeit conduction system impairment, arrhythmias, and valvular abnormalities may also characterize AFD. Even in consideration of pleiotropic manifestation, diagnosis is often challenging. Thus, knowledge of cardiac and extracardiac diagnostic "red flags" is needed to guide a timely diagnosis. Indeed, considering its systemic involvement, a multidisciplinary approach may be helpful in discerning AFD-related cardiac disease. Beyond clinical pearls, a practical approach to assist clinicians in diagnosing AFD includes optimal management of biochemical tests, genetic tests, and cardiac biopsy. We extensively reviewed the current literature on AFD cardiomyopathy, focusing on cardiac "red flags" that may represent key diagnostic tools to establish a timely diagnosis. Furthermore, clinical findings to identify patients at higher risk of sudden death are also highlighted.

[The IN-HF Registry: the history and the scientific production for the Italian cardiology community]. / Il programma IN-HF: la storia e la produzione scientifica a favore della comunità cardiologica italiana.

The Italian Network on Congestive Heart Failure (IN-CHF) project, later known as IN-HF Online, was launched in 1995 to provide the Italian cardiology community with a digital tool, standardized across the country, for managing outpatients with heart failure (HF), that enabled the creation of a database for clinical, educational and scientific purposes. During its almost three decades of activity, this observational research program has achieved highly positive scientific results. Indeed, IN-HF fostered professional relationships among individuals working in different centers, established a cultural network for the care of HF patients, periodically updated on the scientific advances, and allowed the assessment of several clinical, epidemiological, and prognostic features. These findings have been published in numerous national and international journals, as summarized in the present overview.

Heart Failure with Preserved Ejection Fraction: How to Deal with This Chameleon.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a notable heterogeneity in both phenotypic and pathophysiological features, with a growing incidence due to the increase in median age and comorbidities such as obesity, arterial hypertension, and cardiometabolic disease. In recent decades, the development of new pharmacological and non-pharmacological options has significantly impacted outcomes, improving clinical status and reducing mortality. Moreover, a more personalized and accurate therapeutic management has been demonstrated to enhance the quality of life, diminish hospitalizations, and improve overall survival. Therefore, assessing the peculiarities of patients with HFpEF is crucial in order to obtain a better understanding of this disorder. Importantly, comorbidities have been shown to influence symptoms and prognosis, and, consequently, they should be carefully addressed. In this sense, it is mandatory to join forces with a multidisciplinary team in order to achieve high-quality care. However, HFpEF remains largely under-recognized and under-treated in clinical practice, and the diagnostic and therapeutic management of these patients remains challenging. The aim of this paper is to articulate a pragmatic approach for patients with HFpEF focusing on the etiology, diagnosis, and treatment of HFpEF.

[Multidistrict atherosclerotic disease: epidemiological and clinical framework]. / Malattia aterosclerotica polidistrettuale: inquadramento epidemiologico e clinico.

Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.

Right heart failure with left ventricular assist devices: Preoperative, perioperative and postoperative management strategies. A clinical consensus statement of the Heart Failure Association (HFA) of the ESC.

Right heart failure (RHF) following implantation of a left ventricular assist device (LVAD) is a common and potentially serious condition with a wide spectrum of clinical presentations with an unfavourable effect on patient outcomes. Clinical scores that predict the occurrence of right ventricular (RV) failure have included multiple clinical, biochemical, imaging and haemodynamic parameters. However, unless the right ventricle is overtly dysfunctional with end-organ involvement, prediction of RHF post-LVAD implantation is, in most cases, difficult and inaccurate. For these reasons optimization of RV function in every patient is a reasonable practice aiming at preparing the right ventricle for a new and challenging haemodynamic environment after LVAD implantation. To this end, the institution of diuretics, inotropes and even temporary mechanical circulatory support may improve RV function, thereby preparing it for a better adaptation post-LVAD implantation. Furthermore, meticulous management of patients during the perioperative and immediate postoperative period should facilitate identification of RV failure refractory to medication. When RHF occurs late during chronic LVAD support, this is associated with worse long-term outcomes. Careful monitoring of RV function and characterization of the origination deficit should therefore continue throughout the patient's entire follow-up. Despite the useful information provided by the echocardiogram with respect to RV function, right heart catheterization frequently offers additional support for the assessment and optimization of RV function in LVAD-supported patients. In any patient candidate for LVAD therapy, evaluation and treatment of RV function and failure should be assessed in a multidimensional and multidisciplinary manner.

[Gender discrepancy: time to implement gender-based clinical management]. / Position paper ANMCO: Differenze di genere nell'approccio farmacologico cardiovascolare.

It is well established that gender strongly influences cardiovascular risk factors, playing a crucial role in cardiovascular prevention, clinical pathways, diagnostic approach and treatment. Beyond the sex, which is a biological factor, gender entails a socio-cultural condition that impacts access and quality of care due to structural and institutional barriers. However, despite its great importance, this issue has not been adequately covered. Indeed sex and gender differences scarcely impact the clinical approach, creating a lot of disparities in care and outcomes of patients. Therefore, it becomes essential to increase the awareness of the importance of sex and gender influences on cardiovascular diseases. Moreover, new strategies for reducing disparities should be developed. Importantly, these differences should be taken into account in guideline recommendations. In this regard, it is crucial to include a greater number of women in clinical trials, since they are currently underrepresented. Furthermore, more women should be involved as member of international boards in order to develop recommendations and guidelines with more attention to this important topic.The aim of this ANMCO position paper is to shed light on gender differences concerning many cardiovascular drugs in order to encourage a more personalized therapeutic approach.