The paradox of pulmonary arterial hypertension in Italy in the COVID-19 era: is risk of disease progression around the corner?

OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19. MATERIALS AND METHODS: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019. RESULTS: Among 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (p<0.001). A high level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnoses compared with 2019. CONCLUSION: A cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools.

In systemic sclerosis, the TAPSE/sPAP ratio can be used in addition to the DETECT algorithm for pulmonary arterial hypertension diagnosis.

OBJECTIVE: Early detection of pulmonary arterial hypertension (PAH) is crucial for improving patient outcomes. The aim of this study was to compare the positive predictive value (PPV) of the echocardiography-derived tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/sPAP) ratio with that of the DETECT algorithm for PAH screening in a cohort of SSc patients. METHODS: Fifty-one SSc patients were screened for PAH using the DETECT algorithm and echocardiography. RESULTS: Echocardiography was recommended by the DETECT algorithm step 1 in 34 patients (66.7%). Right heart catheterization (RHC) was recommended by the DETECT algorithm step 2 in 16 patients (31.4%). PAH was confirmed by RHC in 5 patients. The DETECT algorithm PPV was 31.3%. The TAPSE/sPAP ratio was higher in SSc patients not referred for RHC than in SSc patients referred for RHC according to the DETECT algorithm step 2 [0.83 (0.35-1.40) mm/mmHg vs 0.74 (0.12-1.09) mm/mmHg, P < 0.05]. Using a cut-off of 0.60 mm/mmHg, 8 (15.7%) SSc patients had a TAPSE/sPAP ratio of ≤0.60 mm/mmHg. PAH was confirmed by RHC in 5 patients. The PPV of TAPSE/sPAP was 62.5%. In multiple regression analysis, TAPSE/sPAP was associated with age [ß coefficient = -0.348 (95% CI: -0.011, -0.003); P < 0.01], DETECT algorithm step 1 [ß coefficient = 1.023 (95% CI: 0.006, 0.024); P < 0.01] and DETECT algorithm step 2 (ß coefficient = -1.758 [95% CI: -0.059, -0.021]; P < 0.0001). CONCLUSION: In SSc patients with a DETECT algorithm step 2 total score of >35, the TAPSE/sPAP ratio can be used to further select patients requiring RHC to confirm PAH diagnosis.

Serum uric acid as a marker of microvascular damage in systemic sclerosis patients.

BACKGROUND: Microvascular damage of skin and internal organs is a hallmark of systemic sclerosis (SSc). Serum uric acid (UA) represents a marker of inflammation and endothelial dysfunction. The aims of this study were to evaluate the correlation between serum UA and intrarenal arterial stiffness evaluated by Doppler ultrasound in SSc patients with normal renal function. We also evaluated the correlation between serum UA and other clinical variables of the disease. METHODS: Forty-five SSc patients underwent clinical assessment, Doppler ultrasound of intrarenal arteries with evaluation of resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D), echocardiography with systolic pulmonary artery pressure (PAPs), baseline pulmonary function tests, and nailfold videocapillaroscopy (NVC). In all patients serum UA was measured. RESULTS: The serum UA showed a significant positive correlation with sCr (r=0.33, p<0.0001) and PAPs (r=0.38, p<0.01) >and negative correlation with CKD-EPI (r=-0.35, p<0.01). The mean value of serum UA increased with severity of NVC damage. Using this cut-off value of 4.7mg/dl, the mean value of Doppler indices of intrarenal stiffness is significantly different (p<0.05) in SSc patients with low normal or high normal serum UA. CONCLUSIONS: Serum UA concentration is higher in patients with high microvascular damage than in patients with low microvascular damage. These preliminary data must be confirmed in large prospective studies.

[Pulmonary hypertension associated with left heart diseases: pathophysiology, diagnosis, treatment]. / Ipertensione polmonare associata ad insufficienza cardiaca: fisiopatologia, diagnosi, terapia.

Pulmonary hypertension (PH) is a common complication of diseases affecting the left heart, mostly found in patients suffering from heart failure. Left atrial hypertension is the initial driver of post-capillary PH. However, several mechanisms may lead in a subset of patients to structural changes in the pulmonary vessels with development of a pre-capillary component. The right ventricle may be frequently affected, leading to right ventricular failure and a worse outcome. The differential diagnosis of PH associated with left heart disease vs pulmonary arterial hypertension (PAH) is challenging in patients with cardiovascular comorbidities, risk factors for PAH and/or a preserved left ventricular ejection fraction. Multidimensional clinical phenotyping is needed to identify patients in whom hemodynamic confirmation is deemed necessary, that may be completed by provocative testing in the cath lab. In contrast with PAH, management of PH associated with left heart disease should focus on the treatment of the underlying condition. There is currently no approved therapy for PH associated with left heart disease: some PAH-specific treatments have led to an increase in adverse events in these patients.

Right ventricular phenotyping in incident patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools. METHODS: Consecutive incident PAH patients aged ≥18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n = 152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n = 143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n = 201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n = 519 patients). Risk stratification was based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) 3-strata model and Registry to Evaluate Early and Long-Term PAH disease Management (REVEAL) 2.0 score. RESULTS: These phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% CI 1.6-2.8, p < 0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% CI 0.18-0.47, p < 0.001). CONCLUSIONS: Echocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients.

In systemic sclerosis TAPSE/sPAP ratio is correlated with ventilatory efficiency and exercise capacity assessed by CPET.

OBJECTIVES: The aim of the study was to evaluate the correlation between cardiopulmonary exercise testing (CPET) parameters and right ventricular echocardiographic parameters for pulmonary arterial hypertension screening in a cohort of systemic sclerosis (SSc) patients. Methods forty SSc patients were examined using CPET and resting transthoracic echocardiography. CPET parameters analyzed were minute ventilation/carbon dioxide production (VE/VCO2) slope and maximum oxygen uptake (VO2 max); echocardiographic parameters were systolic pulmonary artery pressure (sPAP), tricuspid annular plane systolic excursion (TAPSE), and TAPSE/sPAP ratio. Results a positive correlation was observed between VE/VCO2 slope and age (r = 0.415, p < 0.01) and sPAP (r = 0.461, p < 0.01), conversely, a negative correlation was found between VE/VCO2 slope and TASPE/sPAP ratio (r = - 0.521, p = 0.001). VO2 max showed an inverse correlation with age (r = - 0.367, p < 0.05) and sPAP (r = - 0.387, p < 0.05) and a positive correlation with TAPSE/sPAP ratio (r = 0.521, p < 0.01). On stepwise linear regression analysis, VE/VCO2 slope was significantly correlated with TAPSE/sPAP ratio (ß coefficient = - 0.570; p < 0.0001), as well as VO2 max was significantly correlated with TAPSE/sPAP ratio (ß coefficient = 0.518; p = 0.001). Conclusion in SSc patients, TAPSE/sPAP ratio is the echocardiographic parameter of RV function which showed the best correlation with ventilatory efficiency and exercise capacity.

Interleukin-33 and soluble suppression of tumorigenicity 2 in scleroderma cardiac involvement.

Interleukin (IL)-33 is part of the IL-1 family of cytokines and soluble suppression of tumorigenicity 2 (sST2) is part of the family of IL-1 receptors. In systemic sclerosis (SSc), IL-33 and sST2 are involved in cardiac manifestations such as diastolic dysfunction (DD), autonomic dysfunction (AD) and right ventricular-pulmonary arterial coupling assessed by tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP). Serum levels of IL33 and sST2 were assessed in 50 SSc patients and 14 healthy controls (HC). Clinical assessment, echocardiography and heart rate variability (HRV) analysis were performed in SSc patients. Serum levels of IL-33 and sST2 were significantly higher in SSc patients than HC. A linear positive correlation between modified Rodnan skin score and IL33 was observed. Serum values of sST2 were higher in SSc patients with DD than in patients without DD [15403 pg/ml (12,208-19,941) vs 8556 pg/ml (6820-11,036), p < 0.001]. sST2 showed a negative correlation with standard deviation of normal-to-normal RR intervals (SDNN) (r = - 0.281, p < 0.05) and positive correlation with low frequency/high frequency (LF/HF) (r = 0,349, p < 0.01). Negative linear correlation exists between sST2 and TAPSE/sPAP (r = - 0.398, p < 0.01). Serum levels of IL-33 and sST2 are higher in SSc patients than HC. Serum levels of sST2 are a potential marker of DD, AD and right ventricular-pulmonary arterial coupling.

The role of TAPSE/sPAP ratio in predicting pulmonary hypertension and mortality in the systemic sclerosis EUSTAR cohort.

OBJECTIVES: The study aim was to evaluate the predictive role of the echocardiography-derived tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/sPAP) ratio for pulmonary hypertension (PH) diagnosis and mortality in the European Scleroderma Trials and Research (EUSTAR) cohort. METHODS: Eligible patients were systemic sclerosis (SSc) patients registered in the EUSTAR database with at least one visit recording TAPSE and sPAP data. Individual centres were required to provide TAPSE and sPAP data at 12 ± 3 months before right heart catheterization (RHC). Logistic regression analysis was applied to analyse the predictive ability of TAPSE/sPAP ratio for PH diagnosis. Cox regression analysis was performed to evaluate TAPSE/sPAP ratio as a predictive factor for all-cause mortality. RESULTS: 2555 SSc patients met the inclusion criteria for this study with 355 SSc patients having available RHC data at baseline. PH was confirmed by RHC in 195 SSc patients (54.9%). TAPSE/sPAP ratio < 0.55 mm/mmHg [OR 0.251 (95% CI 0.084-0.753), p < 0.05] and FVC/DLCO [OR 2.568 (95% CI 1.227-5.375), p < 0.05] were significantly associated with PH diagnosis. In logistic regression analysis with echocardiographic parameters at 12 ± 3 months before RHC, TAPSE/sPAP ratio < 0.55 mm/mmHg [OR 0.265 (95% CI 0.102-0.685), p < 0.01] and FVC/DLCO [OR 2.529 (95% CI 1.358-4.711), p < 0.01] were associated with PH diagnosis. In multivariate Cox regression analysis, TAPSE/sPAP ratio ≤ 0.32 mm/mmHg [HR 0.310 (0.164-0.585), p < 0.001] was the most significant predictive factor for death. CONCLUSIONS: TAPSE/sPAP ratio < 0.55 mm/mmHg is a predictive risk factor for PH. TAPSE/sPAP ratio ≤ 0.32 mm/mmHg is a predictive risk marker for all-cause mortality.

[Anticoagulation therapy during pulmonary embolism follow-up in clinical practice]. / Gestione della terapia anticoagulante nel follow-up dell'embolia polmonare nella pratica clinica.

Patients with pulmonary embolism are a heterogeneous population and, after the acute phase and the first 3-6 months, the main issue is whether to continue, and hence how long and at what dose, or to stop anticoagulation therapy. In patients with venous thromboembolism (VTE), direct oral anticoagulants (DOACs) are the recommended treatment (class I, level of evidence B in the latest European guidelines), and in most cases, an "extended" or "long-term" low-dose therapy is warranted. This paper aims to provide a practical management tool to the clinician dealing with pulmonary embolism follow-up: from the evidence behind the most used exams (D-dimer, ultrasound Doppler of the lower limbs, imaging tests, recurrence and bleeding risk scores), and the use of DOACs in the extended phase, to six real clinical scenarios with the relative management in the acute phase and at follow-up. Lastly, a practical algorithm is shown to deal with anticoagulation therapy in the follow-up of VTE patients in a simple, schematic, and pragmatic way.

Overview of mitral valve replacement versus mitral valve repair due to ischemic papillary muscle rupture: A meta-analysis inspired by a case report.

BACKGROUND: Papillary muscle rupture (PMR) is an infrequent but catastrophic complication after myocardial infarction (MI). Surgical procedure is considered the optimal treatment, despite high risk. However, the gold standard technique is still a major dilemma. Therefore, a meta-analysis was carried out to assess and provide an overview comparing mitral valve replacement (MVR) and mitral valve repair (MVr) for PMR post-MI. METHODS: A systematic literature search was performed. Data were extracted and verified using a standardized data extraction form. Meta-analysis was realized mainly using RevMan 5.4 software. RESULTS: From four observational studies 1640 patients were identified; 81% underwent MVR and 19% MVr. Operative mortality results were significantly higher in MVR group than the MVr group. MVR was performed under emergency conditions and patients admitted in cardiogenic shock or who required the use of mechanical cardiac support underwent MVR. MVr had shorter time of hospitalization and similar incidence of postoperative complications than MVR. No significant differences existed between the two procedures regarding cardiopulmonary bypass time. CONCLUSIONS: Mitral valve repair appears to be a viable alternative to MVR for post-MI PMR, given that it has lower operative mortality, shorter time of hospitalization and similar incidence of short-term postoperative complications than MVR. However, it needs to be pointed out that MVR was associated with the most critical clinical condition following PMR. There is uncertainty regarding the overall survival and improvement of the quality of life between the procedures. Nevertheless, further completed investigation is required.

The prognostic role of the echocardiographic tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/sPAP) ratio and its relationship with NT-proANP plasma level in systemic sclerosis.

Background: The tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/sPAP) ratio is an echocardiographic estimation of the right ventricle to pulmonary artery (RV/PA) coupling, with a validated prognostic role in different clinical settings. Systemic sclerosis (SSc) patients without evident cardiovascular involvement frequently display subtle RV impairment. The amino-terminal atrial natriuretic peptide (NT-proANP) plasma level relates to SSc disease progression and mortality. We aimed to assess the prognostic value of the TAPSE/sPAP ratio and its relationship with NT-proANP plasma level in SSc patients without overt cardiovascular involvement. Methods: We retrospectively analysed 70 SSc consecutive patients, with no clinical evidence of cardiovascular involvement or pulmonary hypertension (PH), and 30 healthy controls (HC) in a retrospective, single-centre study. All SSc patients underwent recurrent clinical and echocardiographic assessments and NT-proANP plasma level was assessed at baseline. SSc-related cardiovascular events and deaths were extracted during a 6-year follow-up. The complete work-up for the diagnosis, treatment and management of PH performed along the 6 years of follow-up referred to the 2015 European Society of Cardiology guidelines. Results: Systemic sclerosis patients showed lower TAPSE/sPAP ratio at baseline compared to HC [SSc median value = 0.71 mm/mmHg, (IQR 0.62-0.88) vs. HC median value = 1.00 mm/mmHg, (IQR 0.96-1.05); p < 0.001]. Multivariable Cox analysis revealed TAPSE/sPAP ratio as an independent predictor for SSc-related cardiovascular events [HR = 3.436 (95% CI 1.577-7.448); p = 0.002] and mortality [HR = 3.653 (95% CI 1.712-8.892); p = 0.014]. The value of TAPSE/sPAP ratio < 0.7 mm/mmHg was identified as an optimal cut-off for predicting adverse outcomes (p < 0.001) by receiver operating characteristic (ROC) analyses. NT-proANP level significantly related to TAPSE/sPAP ratio (r = 0.52, p < 0.001). TAPSE/sPAP ratio combined with NT-proANP showed an overall significant prognostic role in this SSc population, confirmed by Kaplan-Meier analysis (Log rank p < 0.001). Conclusion: The TAPSE/sPAP ratio, as an index of RV/PA coupling, is an affordable predictor of cardiovascular events and mortality in SSc and, combined with NT-proANP level, may improve the clinical phenotyping and prognostic stratification of SSc patients.

Chronic thromboembolic pulmonary hypertension risk score evaluation and validation (CTEPH SOLUTION): proposal of a study protocol aimed to realize a validated risk score for early diagnosis.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is the most serious long-term complication of acute pulmonary embolism (PE) though it is the only potentially reversible form of pulmonary hypertension (PH). Its incidence is mainly limited to the first 2 years following the embolic event, however it is often underdiagnosed or misdiagnosed. METHODS: This is a multicenter observational cross-sectional and prospective study. Patients with a prior diagnosis of PE will be enrolled and undergo baseline evaluation for prevalent PH detection through a clinical examination and an echocardiogram as first screening exam. All cases of intermediate-high echocardiographic probability of PH will be confirmed by right heart catheterization and then identified as CTEPH through appropriate imaging and functional examinations in order to exclude other causes of PH. A CTEPH Risk Score will be created using retrospective data from this prevalent cohort of patients and will be then validated on an incident cohort of patients with acute PE. RESULTS: One thousand retrospective and 218 prospective patients are expected to be enrolled and the study is expected to be completed by the end of 2021. Up to now 841 patients (620 retrospective and 221 prospective) have been enrolled. CONCLUSIONS: This study is the first large prospective study for the prediction of CTEPH development in patients with PE. It aims to create a comprehensive scoring tool that includes echocardiographic data which may allow early detection of CTEPH and the application of targeted follow-up screening programs in patients with PE.

Circulating NT-proANP level is a predictor of mortality for systemic sclerosis: a retrospective study of an Italian cohort.

Objectives: The authors aimed to evaluate the role of N-terminal proANP (NT-proANP) and of NT-proBNP circulating levels as predictive markers of death due to systemic sclerosis (SSc).Methods: The authors retrospectively enrolled 51 SSc patients. At baseline, NT-proBNP and NT-proANP circulating levels and clinical features were collected. Date and causes of death were extracted during a 6-year follow-up.Results: 13 SSc patients (23.2%) died for SSc complications (9 for interstitial lung disease and 4 for pulmonary arterial hypertension). The median NT-proBNP plasma level did not significantly differ (p > 0.05) in SSc patients died or alive [645 (448-1026) fmol/ml vs 592 (409-789) fmol/ml]. The median NT-proANP plasma level was significantly (p < 0.01) higher in SSc died than in SSc patients alive [4000 (2100-6722) fmol/ml vs 1640 (1381-2721) fmol/ml]. The Kaplan-Meier analysis revealed that SSc patients with increased NT-proANP level had increased mortality (p < 0.05). In the multivariate analysis, DLco [HR 0.966 (0.934-0.999), p < 0.05] and NT-proANP level [HR 1 (1-1), p < 0.05] were predictive markers of death due to SSc.Conclusions: NT-proANP plasma level is a predictive marker of death due to SSc.

Atrial natriuretic peptide predicts disease progression and digital ulcers development in systemic sclerosis patients.

AIMS: Systemic sclerosis (SSc) is an autoimmune disease characterized by micro/macrovascular damage due to the underlying fibrosis. Markers able to predict the progression of cardiovascular damage, including digital ulcers, in SSc are warranted. We aimed at characterizing the relevance of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide plasma levels in relation to cardiovascular damage and digital ulcers in a cohort of Italian SSc patients. METHODS: Seventy patients were enrolled (64 women and six men; mean age 56.7 ±â€Š14 years) with a disease duration of 11.1 ±â€Š8.3 years. Clinical, instrumental (nailfold videocapillaroscopy, ECG, transthoracic echocardiography, pulmonary function test with diffusion lung CO), NT-proANP and N-terminal probrain natriuretic peptide plasma levels measurement were performed at baseline. The clinical follow-up lasted 24 months. The statistical approach used to achieve the study objectives included multivariate analysis, receiver operating characteristic curve, Kaplan-Meier and Cox regression analyses. RESULTS: Both NT-proNPs levels correlated with systolic pulmonary arterial pressure, but only the NT-proANP level correlated with right heart dimension. Both NT-proNPs levels were higher in patients experiencing events at follow-up but only the NT-proANP level significantly predicted the progression of cardiovascular damage, including development of pulmonary arterial hypertension (PAH). NT-proANP levels were higher in patients with digital ulcers and strongly predicted their development. CONCLUSION: Our results show that the NT-proANP plasma level significantly correlates with disease progression such as new onset of PAH, worsening of pulmonary hypertension and development of digital ulcers in a cohort of SSc Italian patients. If future studies will confirm our findings, the plasma NT-proANP level could be used in clinical practice as a novel sensitive marker for PAH and digital ulcers development in SSc.

Role of autonomic dysfunction in the regulation of myocardial blood flow in systemic sclerosis evaluated by cardiac magnetic resonance.

AIM: Autonomic dysfunction (AD) is an early feature of systemic sclerosis (SSc). A regular endothelial function is a prerequisite for normal response of the myocardial blood flow (MBF) to cold pressure test (CPT). The aim of the study was to evaluate the relation between MBF and AD at rest and after CPT in asymptomatic SSc patients. METHODS: Twenty SSc patients and 10 age-, sex- and body mass index-matched healthy controls underwent cardiac magnetic resonance at rest and after CPT. All subjects underwent 24 hours ambulatory 3-channel electrocardiogram Holter to evaluate AD by heart rate variability. RESULTS: We did not observe any significant difference in MBF (mL/g/min) at rest and after CPT between SSc patients and healthy controls. Delta of MBF (difference between MBF after CPT and rest MBF) was lower (P = 0.039) in SSc patients than healthy controls (0.28 [0.04-0.40] vs 0.33 [0.24-0.54]). The low frequency/high frequency (LF/HF) was higher (P = 0.002) in SSc patients than healthy controls (3 [1.7-6] vs 1.8 [1.1-2.8]). The high frequencies (HF), modulated mainly by paraympathetic system, was lower (P = 0.003) in SSc patients than healthy controls (30 [16-42] vs 36.5 [24-44]). Sympathetic hyperactivity, due to reduction of parasympathetic activity (HF), is present in SSc patients. A negative correlation was observed between Delta of MBF and LF/HF (r = -0.572, P = 0.0031). CONCLUSION: AD, characterized by sympathovagal imbalance due to a reduced parasympathetic tone with high LF/HF ratio, could be responsible for the reduced myocardial vasodilatory response after CPT.

Pulmonary hypertension and clinical correlates in hypertrophic cardiomyopathy.

BACKGROUND: Pulmonary hypertension (PH) in patients with hypertrophic cardiomyopathy (HCM) has been investigated in a small number of studies. Purpose of this study was to assess the prevalence and its association with outcome in a population of consecutive HCM outpatients. METHODS: We retrospectively analyzed data of 361 consecutive HCM outpatients in whom echocardiographic measurements of pulmonary artery systolic pressure (PASP) were available at initial and most recent evaluation. Four different clinical groups were specifically investigated: patients without left ventricular outflow tract obstruction (group A, 165), with obstruction (group B, 126), patients diagnosed at the age≥65 (group C, 50) and patients with end stage (ES) HCM (group D, 20). RESULTS: PH was identified in 41 (11.4%) of the 361 patients at initial evaluation while it has been recognized in 25 (7,8% [1.1%/year]) during a median follow-up of 3.4years. Analysis of subgroups showed that prevalence of PH increased from patient group A to D (8%, group A, 19%, group B, 28% group C, 70%, group D, respectively, p<0,01). During follow-up, patients with PH showed a significant higher HCM-related mortality (p=0.01) and morbidity (p<0.001) as compared with those without PH, but in multivariable analysis, PH resulted an independent risk factor only for HCM-related morbidity (HR=2.50, 95% CI 1.08-5.79, p=0.03). CONCLUSION: PH affects a significant proportion of patients with HCM. Its prevalence varies according to different clinical profiles. It is associated with an unfavorable clinical outcome and is an independent predictor of morbidity.

The cardiac magnetic resonance in the diagnosis of cardiac Raynaud phenomenon in a patient with systemic sclerosis: case report and review of literature.

Raynaud phenomenon (RP) is the hallmark of Systemic Sclerosis (SSc). Visceral RP has also been proposed in SSc patients. Cardiac Raynaud's phenomenon (C-RP) was evaluated in a few clinical studies both as cold-induced transient myocardial ischaemia and as presence of advanced myocardial fibrosis and contraction band necrosis in autopsied patients. Until today numerous techniques, such as scintigraphy and myocardial contrast echocardiography, have been used to evaluate C-RP. In this case report for the first time we have used Cardiac Magnetic Resonance (CMR) after cold test to demonstrate the presence of the C-RP. In addition we have shown that therapy with Iloprost can be used to reduce episodes of C-RP.

Left Ventricular Mass and Intrarenal Arterial Stiffness as Early Diagnostic Markers in Cardiorenal Syndrome Type 5 due to Systemic Sclerosis.

BACKGROUND: Cardiorenal syndrome type 5 (CRS-5) includes a group of conditions characterized by a simultaneous involvement of the heart and kidney in the course of a systemic disease. Systemic sclerosis (SSc) is frequently involved in the etiology of acute and chronic CRS-5 among connective tissue diseases. In SSc patients, left ventricular mass (LVM) can be used as a marker of nutritional status and fibrosis, while altered intrarenal hemodynamic parameters are suggestive of early kidney involvement. METHODS: Forty-two consecutive patients with a diagnosis of SSc without cardiac and/or renal impairment were enrolled to assess whether cardiac muscle mass can be related to arterial stiffness. Thirty subjects matched for age and sex were also enrolled as healthy controls (HC). All patients performed echocardiography and renal ultrasound. RESULTS: Doppler indices of intrarenal stiffness and echocardiographic indices of LVM were significantly increased in SSc patients compared to HC. A positive correlation exists between LVM/body surface area and pulsatile index (p < 0.05, r = 0.36), resistive index (p < 0.05, r = 0.33) and systolic/diastolic ratio (p < 0.05, r = 0.38). Doppler indices of intrarenal stiffness and LVM indices were significantly higher in SSc patients with digital ulcers than in SSc patients without a digital ulcer history. CONCLUSIONS: SSc is characterized by the presence of microvascular and multiorgan injury. An early cardiac and renal impairment is very common. LVM and intrarenal arterial stiffness can be considered as early markers of CRS onset. The clinical use of these markers permits a prompt identification of organ damage. An early diagnosis allows the appropriate setting of pharmacological management, by slowing disease progression. © 2016 S. Karger AG, Basel.