La disfunzione microvascolare coronarica nelle patologie endocrine ed infiammatorie

It has recently been proven that endothelial dysfunction is an early step in the development of atherosclerosis and is mainly characterized by a reduction in the bioavailability of nitric oxide. Nowadays atherosclerosis is considered as a complex inflammatory and immune-mediated process in which leukocytes and soluble factors are crucially involved in causing vessel injury. Furthermore inflammatory and endocrine disease although dimostrated to be at increased risk for cardiovascular mortality, are poorly investigated on this point of view. Emerging evidence indicates a significant role played by endothelium also in the onset and progression of the cardiac allograft vasculopathy (CAV), a peculiar type of coronary atherosclerosis which is considered the main limiting factor of long term outcome after heart transplantantion. CAV involves both major epicardial and intramyocardial vessels. The dysfunction of the microvascular system is a variable prhenomenon over time, as in the epicardial tree. In this thesis we aimed to investigate the coronary flow reserve (CFR) in patients without evidence for epicardial coronary disease, affected by inflammatory and endocrine disease. Moreover we wanted to valuate the coronary microvascular function in heart transplantantion in order to better understand the CAV pathophysiolog

Long-term prognostic value of coronary flow reserve in psoriasis patients

BACKGROUND AND AIMS Psoriasis affects more than 3% of the general population and is associated with an increased risk of premature cardiovascular events and death. We assessed the prognostic role of coronary flow reserve (CFR) as a marker of coronary microvascular function in psoriasis patients asymptomatic for cardiovascular disease. METHODS We retrospectively analyzed 153 prospectively collected patients affected by psoriasis (123 male; age 36 ± 8 years) without cardiovascular disease. CFR in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. CFR was the ratio of hyperemic to resting diastolic flow velocity. CFR ≤2.5 was the cut off to define the presence of coronary microvascular dysfunction (CMD). RESULTS CMD was present in 23 patients (15%). Multivariable logistic regression analysis showed that CMD was associated with severe psoriasis (OR 3.1, p = 0.03), psoriatic arthritis (OR 2.9, p = 0.03), hypertension (OR 4.1, p = 0.009), and time elapsing since psoriasis diagnosis >6 years (OR 1.9, p = 0.03). Patients with CFR ≤2.5 had a lower survival free from events (p < 0.0001). CONCLUSIONS In psoriasis patients, CFR may be a reliable prognostic marker for cardiovascular event-free survival and may help identify patients at higher risk of developing cardiovascular complications. Whether novel biologic therapies able to reduce skin disease will improve CMD and prognosis in these patients needs to be further studied, prospectively

Coronary Microvascular Dysfunction Induced by Primary Hyperparathyroidism is Restored After Parathyroidectomy

Background— Symptomatic primary hyperparathyroidism (PHPT) is associated with increased cardiovascular mortality. However, data on the association between asymptomatic PHPT and cardiovascular risk are lacking. We assessed coronary flow reserve (CFR) as a marker of coronary microvascular function in asymptomatic PHPT of recent onset. Methods and Results— We studied 100 PHPT patients (80 women; age, 58±12 years) without cardiovascular disease and 50 control subjects matched for age and sex. CFR in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. CFR was the ratio of hyperemic to resting diastolic flow velocity. CFR was lower in PHPT patients than in control subjects (3.0±0.8 versus 3.8±0.7; P <0.0001) and was abnormal (≤2.5) in 27 patients (27%) compared with control subjects (4%; P =0.0008). CFR was inversely related to parathyroid hormone (PTH) levels ( r =−0.3, P <0.004). In patients with CFR ≤2.5, PTH was higher (26.4 pmol/L [quartiles 1 and 3, 16 and 37 pmol/L] versus 18 [13–25] pmol/L; P <0.007), whereas calcium levels were similar (2.9±0.1 versus 2.8±0.3 mmol/L; P =0.2). In multivariable linear regression analysis, PTH, age, and heart rate were the only factors associated with CFR ( P =0.04, P =0.01, and P =0.006, respectively). In multiple logistic regression analysis, only PTH increased the probability of CFR ≤2.5 ( P =0.03). In all PHPT patients with CFR ≤2.5, parathyroidectomy normalized CFR (3.3±0.7 versus 2.1±0.5; P <0.0001). Conclusions— PHPT patients have coronary microvascular dysfunction that is completely restored after parathyroidectomy. PTH independently correlates with the coronary microvascular impairment, suggesting a crucial role of the hormone in explaining the increased cardiovascular risk in PHPT

332 Clinical and prognostic significance of junctional late gadolinium enhancement in patients with non-ischaemic cardiomyopathy

Abstract Aims Pulmonary hypertension (PH) carries a poor prognosis in patients with non-ischaemic dilated cardiomyopathy (NIDC). Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) evaluation can identify myocardial abnormalities. In particular, junctional LGE is already an established marker of adverse right ventricular (RV) remodelling in patients with pre-capillary PH. This study sought to assess the prevalence of junctional LGE by CMR in NIDC, its relationship with hemodynamic parameters and, moreover, its prognostic significance. Methods and results Patients with NIDC who underwent right heart catheterization (RHC) and CMR within 3 months in a tertiary hospital were enrolled. Patients with acute heart failure were excluded. Among others, RV and left ventricular (LV) volumes, junctional LGE at CMR, pulmonary artery pressure (PAP) and pulmonary capillary wedge pressure (PCWP) at RHC were tabulated. Pulmonary hypertension was defined accordingly to current Guidelines (median PAP at RHC ≥ 25 mmHg). The primary endpoint consisted of heart failure (HF) hospitalization during follow-up. A total of 188 patients [median age 49 (SD 15), 71% males] were evaluated. At morpho-functional CMR evaluation, most subjects (76%) had important systolic dysfunction (LV EF ≤ 35%). Junctional LGE was observed in 83 (44%) patients. Among patients with junctional LGE, 21 had LGE confined only to the junctional region, while 61 had also mid-wall interventricular septal stria and 21 a mid-wall stria in the lateral free LV wall. Patients with junctional LGE had lower RV EF (49% vs. 56%, P &lt; 0.001) and LV EF (27% vs. 30%, P = 0.012) when compared to those without junctional LGE although no differences in LV and RV dimensions were found. RHC showed PH in 83 patients (44%). Patients with junctional LGE showed a worse hemodynamic profile in terms of PH (55% vs. 36%; P = 0.011) and increase in PCWP (PCWP &gt; 15 mmHg in 60% vs. 42%; P = 0.015) compared to subjects without junctional LGE. Among 79 patients with PH and PCWP &gt; 15 mmHg, 75 (95%) had a combined post capillary and pre-capillary PH (diastolic pressure gradient ≥7 mmHg). Univariate analysis showed that junctional LGE was associated with a worse hemodynamic profile; on multivariable model, RV EF was significantly associated with the presence of junctional LGE (OR: 0.91; 95% CI: 0.87–0.96, P &lt; 0.001). During a median follow-up of 58 months, 33 patients (18%) died or underwent heart transplantation/ventricular assist device implantation, 17% in the junctional LGE group vs. 18% among those without junctional LGE. Thirty-eight patients (20%) had at least one episode of HF, 22 among junctional LGE group and 16 in control group (27% vs. 15%, P = 0.056). When adjusted for age, junctional LGE resulted a significant determinant of HF hospitalization (OR: 2.13, 95% CI: 1.02–4.44, P = 0.044). Conclusions Junctional LGE is detectable in almost half of NIDC patients and it is related to a worse haemodynamic profile, characterized by PH and elevated PCWP. Moreover, after adjustment for age, it was a significant determinant of HF hospitalization during follow-up in our population. Junctional LGE can therefore represent a useful prognostic tool, as marker of adverse ventricular remodelling likely related to ventricular interdependence

La disfunzione microvascolare coronarica nelle patologie endocrine ed infiammatorie

It has recently been proven that endothelial dysfunction is an early step in the development of atherosclerosis and is mainly characterized by a reduction in the bioavailability of nitric oxide. Nowadays atherosclerosis is considered as a complex inflammatory and immune-mediated process in which leukocytes and soluble factors are crucially involved in causing vessel injury. Furthermore inflammatory and endocrine disease although dimostrated to be at increased risk for cardiovascular mortality, are poorly investigated on this point of view. Emerging evidence indicates a significant role played by endothelium also in the onset and progression of the cardiac allograft vasculopathy (CAV), a peculiar type of coronary atherosclerosis which is considered the main limiting factor of long term outcome after heart transplantantion. CAV involves both major epicardial and intramyocardial vessels. The dysfunction of the microvascular system is a variable prhenomenon over time, as in the epicardial tree. In this thesis we aimed to investigate the coronary flow reserve (CFR) in patients without evidence for epicardial coronary disease, affected by inflammatory and endocrine disease. Moreover we wanted to valuate the coronary microvascular function in heart transplantantion in order to better understand the CAV pathophysiologyLa disfunzione endoteliale, che caratterizza la malattia aterosclerotica fin dagli esordi, è causata principalmente da una ridotta biodisponibilità di ossido nitrico. Ai giorni d’oggi l’aterosclerosi è considerata un complesso processo infiammatorio-immunitario nel quale i leucociti, i fattori solubili e il complemento svolgono un ruolo cruciale nello sviluppo e nel progredire di tale patologia. Inoltre, oltre alle comuni patologie note per avere maggiore incidenza di aterosclerosi, quali il diabete, ve ne sono molte altre, quali quelle endocrine e infiammatorie, che sembrano avere un maggiore rischio cardiovascolare, ma poco chiari sono i meccanismi che sottendono a tale aumentato rischio. Sempre maggiori evidenze indicano un ruolo della disfunzione endoteliale anche per quanto riguarda l’insorgenza e la progressione della vasculopatia cardiaca del graft, un tipo peculiare di aterosclerosi, a tutt’oggi considerata il maggiore fattore limitante la sopravvivenza del graft cardiaco. La Vasculopatia cardiaca del graft coinvolge sia i vasi epicardici che il microcircolo. Come per l’albero coronarico epicardico, la disfunzione microvascolare è un fenomeno variabile nel tempo. In questa tesi noi abbiamo voluto indagare la riserva di flusso coronarico (CFR) in pazienti senza evidenza di stenosi epicardiche, affetti da patologie infiammatorie ed endocrine. Inoltre abbiamo voluto valutare la funzione microvascolare coronarica nel trapianto cardiaco per meglio comprendere la fisiopatologia della CA

Multiparametric analysis of coronary flow in psoriasis using a coronary flow reserve companion

BACKGROUND Coronary microvascular dysfunction (CMD) is usually evaluated measuring coronary flow velocity reserve (CFVR). A more comprehensive analysis of CFVR including additional consideration of the associated logical companion-CFVR, where hyperemic diastolic coronary flow velocity may act as surrogate, was applied in this study to elucidate the mechanism of CMD in psoriasis. METHODS AND RESULTS Coronary flow velocity reserve was analysed using transthoracic echocardiographs of 127 psoriasis patients (age 36 ± 8 years; 104 males) and of 52 sex- and age-matched healthy controls. CFVR determination was repeated in the patient subgroup (n = 78) receiving anti-inflammatory therapy. Baseline and hyperemic microvascular resistance (MR) were calculated. CMD was defined as CFVR ≤ 2.5. Four endotypes of CMD were identified referring to concordant or discordant impairments of hyperemic flow or CFVR. We evaluated the companion-CFVR, as derived from the quadratic mean of hyperemic and diastolic flow velocity at rest. Coronary flow parameters, including CFVR (p = 0.01), were different among the two endotypes having CFVR > 2.5. Specifically, all 11 (14%) patients with CFVR deterioration despite therapy, belonged to endotype 1, and had higher baseline and hyperemic MR (p < 0.0001, both). Interestingly, while CFVR was comparable in patients with worsened versus those with improved CFVR, the companion-CFVR could discriminate by being lower in patients with worsened CFVR (p = 0.01). CONCLUSIONS The reduced CFVR in psoriasis is driven by decreased companion-CFVR, combined with increased hyperemic MR. Adoption of the mandatory companion-CFVR enables a personalized characterization superior to that achieved by exclusive consideration of CFVR

Pulmonary arterial hypertension in connective tissue disorders: Pathophysiology and treatment

Our article focuses on the pathogenesis and treatment of CTD-PAH. In the latest ESC/ESR guidelines for PAH, the authors underline that although CTD-PAH should follow the same treatment protocol as idiopathic PAH, the therapeutic approach is more complex and difficult in the former. This review throws light on several peculiar aspects of CTD-PAH and the latest findings in the pathogenesis, namely, the role of inflammation in the maladaptive right ventricle remodeling in SSc-PAH where immunosuppressants are classically believed to be ineffective. Furthermore, we discuss the major critical points in the therapy of CTD-PAH which is one of the strengths of our article. To the best of our knowledge, there are no other reviews that exclusively focus on the pathogenesis and treatment of CTD-PAH patients, with an emphasis on the more critical issues. Thus, it is our contention that our work would be of interest to the readers

Serum Biomarkers in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening complication of connective tissue diseases (CTDs) characterised by increased pulmonary arterial pressure and pulmonary vascular resistance. CTD-PAH is the result of a complex interplay among endothelial dysfunction and vascular remodelling, autoimmunity and inflammatory changes, ultimately leading to right heart dysfunction and failure. Due to the non-specific nature of the early symptoms and the lack of consensus on screening strategies—except for systemic sclerosis, with a yearly transthoracic echocardiography as recommended—CTD-PAH is often diagnosed at an advanced stage, when the pulmonary vessels are irreversibly damaged. According to the current guidelines, right heart catheterisation is the gold standard for the diagnosis of PAH; however, this technique is invasive, and may not be available in non-referral centres. Hence, there is a need for non-invasive tools to improve the early diagnosis and disease monitoring of CTD-PAH. Novel serum biomarkers may be an effective solution to this issue, as their detection is non-invasive, has a low cost and is reproducible. Our review aims to describe some of the most promising circulating biomarkers of CTD-PAH, classified according to their role in the pathophysiology of the disease