Frequency, characteristics and risk assessment of pulmonary arterial hypertension with a left heart disease phenotype.

AIM: To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD). METHODS AND RESULTS: By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to determine risk of death at baseline and at first follow-up with COMPERA and COMPERA 2.0 scores. Fifty seven (20%) had PAH-LHD according to the AMBITION definition. Compared with no-LHD ones, they were older, had higher BMI, more cardiovascular comorbidities, higher E/e' ratio and left atrial area, but lower BNP concentrations and better right ventricular function and pulmonary hemodynamics. Survival was comparable between PAH-LHD and no-LHD patients, although the former were less commonly treated with dual PAH therapy. Both COMPERA and COMPERA 2.0 discriminated all-cause mortality risk of PAH-LHD at follow-up, but not at baseline. Risk profile significantly improved during follow-up only when assessed by COMPERA 2.0. At multivariable analysis with low-risk status as reference, intermediate-high and high-risk, but not LHD phenotype, were associated with higher hazard of all-cause mortality. Results were comparable in secondary analyses including patients in the last 10 years and atrial fibrillation and echocardiographic abnormalities as additional criteria for PAH-LHD. CONCLUSIONS: In real life, PAH-LHD patients are frequent, have less severe disease and are less likely treated with PAH drug combinations than no-LHD. The COMPERA 2.0 model may be more appropriate to evaluate their mortality risk during follow-up and how it is modulated by therapy.

Pharmacoutilization and adherence to sacubitril/valsartan in real world: the REAL.IT study in HFrEF.

AIMS: The current European Society of Cardiology (ESC) guidelines provide clear indications for the treatment of acute and chronic heart failure (HF). Nevertheless, there is a constant need for real-world evidence regarding the effectiveness, adherence, and persistence of drug therapy. We investigated the use of sacubitril/valsartan for the treatment of HF with reduced ejection fraction in real-world clinical practice in Italy. METHODS AND RESULTS: An observational, retrospective, non-interventional cohort study based on electronic medical records from nine specialized hospital HF centres in Italy was carried out on patients with prescription of sacubitril/valsartan. Overall, 948 patients had a prescription of sacubitril/valsartan, with 924 characterized over 6 months and followed up for 12 months. Pharmacoutilization data at 1 year of follow-up were available for 225 patients {mean age 69.7 years [standard deviation (SD) = 10.8], 81.8% male}. Of those, 398 (45.2%) reached the target dose of sacubitril/valsartan of 97/103 mg in a mean time of 6.9 (SD = 6.2) weeks. Blood pressure and hypotension in 61 patients (65%) and worsening of chronic kidney disease in 10 patients (10.6%) were the main reasons for not reaching the target dose. Approximatively 50% of patients had a change in sacubitril/valsartan dose during follow-up, and 158 (70.2%) were persistent with the treatment during the last 3 months of follow-up. A sensitivity analysis (persistence during the last 4 months of follow-up) showed persistence for 162 patients (72.0%). Adherence data, available for 387 patients, showed full adherence for 205 (53%). Discontinuation (102/717 patients, 14.2%) was mainly due to hypotension and occurred after a mean time of 34.3 (SD = 28.7) weeks. During follow-up, out of 606 patients with available data, 434 patients (71.6%) had an HF add-on drug or drugs concomitant with sacubitril/valsartan. HF-related hospitalization during follow-up was numerically higher in non-persistent (16/67 patients, 23.9%) vs. patients persistent to sacubitril/valsartan (30/158, 19%) (P = 0.405). CONCLUSIONS: Real-world data on the use of sacubitril/valsartan in clinical practice in Italy show a rapid titration to the target dose, high therapeutic adherence enabling a good level of therapeutic management in line with ESC guidelines for patients with reduced ejection fraction.

Performance of risk stratification scores and role of comorbidities in older vs younger patients with pulmonary arterial hypertension.

BACKGROUND: Risk scores are important tools for the prognostic stratification of pulmonary arterial hypertension (PAH). Their performance and the additional impact of comorbidities across age groups is unknown. METHODS: Patients with PAH enrolled from 2001 to 2021 were divided in ≥65 years old vs <65 years old patients. Study outcome was 5-year all-cause mortality. French Pulmonary Hypertension Network (FPHN), FPHN noninvasive, Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL 2.0) risk scores were calculated and patients categorized at low, intermediate and high risk. Number of comorbidities was calculated. RESULTS: Among 383 patients, 152 (40%) were ≥65 years old. They had more comorbidities (number of comorbidities 2, IQR 1-3, vs 1, IQR 0-2 in <65 years patients). Five-year survival was 63% in ≥65 vs 90% in <65 years. Risk scores correctly discriminated the different classes of risk in the overall cohort and in the older and younger groups. REVEAL 2.0 showed the best accuracy in the total cohort (C-index 0.74, standard error-SE- 0.03) and older (C-index 0.69, SE 0.03) patients, whereas COMPERA 2.0 performed better in younger patients (C-index 0.75, SE 0.08). Number of comorbidities was associated with higher 5-year mortality, and consistently increased the accuracy of risk scores, in younger but not in older patients. CONCLUSIONS: Risk scores have similar accuracy in the prognostic stratification of older vs younger PAH patients. REVEAL 2.0 had the best performance in older patients and COMPERA 2.0 had it in younger patients. Comorbidities increased the accuracy of risk scores only in younger patients.

Sacubitril/Valsartan in Heart Failure with Reduced Ejection Fraction: Real-World Experience from Italy (the REAL.IT Study).

Sacubitril/valsartan reduces heart failure (HF)-related hospitalizations and cardiovascular mortality in PARADIGM-HF and has become a foundational treatment for HF with reduced ejection fraction (HFrEF). However, data of its routine real-world use are limited, and evidence from Italian settings is lacking. The REAL.IT study aimed to characterize the demographics, pharmacotherapy, clinical characteristics and outcomes of sacubitril/valsartan-treated Italian patients with HFrEF. Electronic medical records of patients initiating sacubitril/valsartan from October 2016 to June 2019 at nine specialized hospital outpatient HF centers across Italy were reviewed. Overall, 924 adults (mean age 64.5 years, 84.6% male) were included. At baseline, 38.7% had an ischemic HF etiology, 45.9% hypertension, 23.2% atrial fibrillation, 25.4% diabetes mellitus, 26.1% an implantable cardioverter-defibrillator and 31.9% coronary artery bypass grafting. There were no clear patterns of patient selection over time. During follow-up, NYHA class improved in 37.5% of patients after a mean of 5.3 ± 3.8 months; 36.1% and 16.7% of patients were in NYHA class III during characterization and after one year of follow-up, respectively. Left ventricular ejection fraction (LVEF) improved ≥5% in 56.3% of patients at one year; 39.7% had ≥30% reduction of N-terminal pro-B-type natriuretic peptide; 2.2% had hyperkalemia during characterization and 2.6% during follow-up; and 3.8% had hypotension during characterization and 12% during follow-up. A total of 50 (5.8%) of patients had device implantation (ICD/CRT) during follow-up. HF-related hospitalization was recorded in 19.6% of patients during follow-up; 3.8% of patients died, approximately 1.3% from cardiovascular causes. Our real-world data confirm the favorable effectiveness and tolerability of sacubitril/valsartan observed in pivotal randomized controlled trials.

Leflunomide-induced pulmonary arterial hypertension: Case report and review of literature.

Leflunomide, an isoxazole derivative, is a disease-modifying antirheumatic drug, that has successfully been used for the treatment of rheumatoid arthritis and psoriatic arthritis as a feasible alternative to methotrexate. Among side effects, pulmonary arterial hypertension (PAH) has been described in a few case reports.We present a 55-year-old woman treated with leflunomide for psoriatic spondyloarthritis who consulted our hospital because of progressive exertional dyspnea. Clinical examination found signs of right heart failure and severe pre-capillary pulmonary hypertension (PH) was diagnosed by right heart catheterization. All investigations for pre-capillary PH were negative and a diagnosis of severe PAH was thus established. Due to previous evidence of the association of leflunomide with PAH, the drug was stopped and upfront dual combination therapy with pulmonary vasodilators was initiated. The patient's condition rapidly improved with significant improvement in exercise tolerance and normalization of echocardiographic right ventricular systolic pressure within three months of treatment. Learning objective: Pulmonary arterial hypertension (PAH) is a rare disease and drug-induced causes account for only a small percentage of these patients. In recent years, new drugs have been identified or suspected as potential risk factors for PAH. Among these, leflunomide, a disease-modifying antirheumatic drug, has been associated with PAH only in a few case reports. An accurate drug history is strongly recommended for all patients in which a PAH is newly diagnosed.

Prognostic role of global longitudinal strain by feature tracking in patients with hypertrophic cardiomyopathy: The STRAIN-HCM study.

BACKGROUND: The assessment of myocardial fiber deformation with cardiac magnetic resonance feature tracking (CMR-FT) has shown to be promising in terms of prognostic information in several structural heart diseases. However, little is known about its role in hypertrophic cardiomyopathy (HCM). Aims of the present study were: 1) to assess the prognostic role of CMR-FT derived strain parameters in patients with HCM. METHODS: CMR was performed in 130 consecutive HCM patients (93 males, mean age (54 ± 17 years) with an estimated 5-year risk of sudden cardiac death (SCD) <6% according to the HCM Risk-SCD calculator. 2D- and 3D-Global Radial (GRS), Longitudinal (GLS) and Circumferential (GCS) Strain was evaluated by FT analysis. The primary outcome of the study was a composite of major adverse cardiac events (MACE) including SCD, resuscitated cardiac arrest due to ventricular fibrillation (VF) or hemodynamically unstable ventricular tachycardia (VT), and hospitalization for heart failure. RESULTS: After a median follow-up of 51.7 (37.1-68.8) months, 4 (3%) patients died (all of them suffered from SCD) and 36 (28%) were hospitalized for heart failure. After multivariable adjustment for clinical and imaging covariates, among all strain parameters, only GLS remained a significant independent predictor of outcome events in both the model including 2D strain (HR 1.12, 95% CI 1.03-1.23, p = 0.01) and the model including 3D strain (HR 1.14, 95% CI 1.01-1.30, p = 0.04). The addition of 2D-GLS into the model with clinical and imaging predictors resulted in a significant increase in the C-statistic (from 0.48 to 0.65, p = 0.03). CONCLUSION: CMR-FT derived GLS is a powerful independent predictor of MACE in patients with HCM, incremental to common clinical and CMR risk factors including left ventricular ejection fraction and late gadolinium enhancement.

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.

Major rectus abdominis hematoma complicating low molecular weight heparin therapy.

The use of low molecular weight heparin sometimes leads to major life threatening complications, such as acute abdominal haemorrhages. We report two cases of major haematoma of rectus abdominis. Computed tomography was very helpful to confirm the diagnosis in these cases.

Late coronary thrombosis in paclitaxel-eluting stents. Case reports.

Drug-eluting stent (DES) implantation has reduced angiographic and clinical restenosis that actually develops in less than 10% of treated patients. DESs also tend to delay the endothelialisation process increasing the risk of stent thrombosis. Subacute stent thrombosis may complicate long-term success of coronary angioplasty; it is a sudden event and usually causes acute myocardial infarction or sudden cardiac death. Patients undergoing DES implantation should be treated with dual antiplatelet therapy for at least 3-6 months. We describe two cases presenting with ST-elevation acute myocardial infarction due to stent thrombosis that occurred late after deployment of a paclitaxel-eluting stent, after discontinuation of antiplatelet therapy. It is important, for clinical cardiologists and general practitioners, to know the potential risk of late thrombosis of DES patients and, consequently, the implications regarding management of antiplatelet therapy.

Prognostic role of non-sustained ventricular tachycardia in a large cohort of patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The identification of patients with idiopathic dilated cardiomyopathy (IDC) at higher risk of sudden death (SD) is still an unsolved issue, and the role of non-sustained ventricular tachycardia (NSVT) uncertain. METHODS: The effect of NSVT on total mortality, SD and life-threatening arrhythmias was evaluated in 554 patients with IDC on optimal medical treatment and at long-term follow-up (81 +/- 58 months). RESULTS: At diagnosis, 240 patients (43%) had NSVT at Holter monitoring and 314 (57%) did not. During follow-up, 189 patients (5/100 patients-year) died or underwent heart transplantation; SD occurred in 53 patients (1.4/100 patients-year); SD + non-fatal ventricular arrhythmias occurred in 75 patients (2/100 patients-year). Patients with and without NSVT at diagnosis had the same 5-year transplant-free survival rate (76 vs 76%, p = NS) and a similar incidence of SD (10 vs 7%, p = NS). The length and rate of NSVT did not show any significant relationship with the outcome. Only heart failure symptoms (NYHA class III-IV) (hazard ratio [HR] 1.9, p = 0.015) and severe left ventricular impairment (left ventricular ejection fraction < or = 0.30 and left ventricular end-diastolic diameter > or = 70 mm) (HR 2.7, p < 0.0001) were independently associated with higher SD risk. At multivariate analysis the presence of frequent NSVT episodes (> or = 3 runs/day) was associated with an increased risk of total mortality (HR 1.68, p = 0.041) and of major ventricular arrhythmias (HR 2.11, p = 0.037), but only in the subgroup of patients with severe left ventricular impairment. CONCLUSIONS: Patients with advanced heart failure symptoms, severe left ventricular dysfunction and dilation had a higher risk of SD independently of NSVT. The finding of more frequent NSVT was associated with an increased risk of all-cause mortality and of major ventricular arrhythmias in patients with severe left ventricular impairment.

Idiopathic dilated cardiomyopathy: prognostic significance of electrocardiographic and electrophysiologic findings in the nineties.

BACKGROUND: With the exception of a few cases such as aborted sudden cardiac death, sustained ventricular tachycardia, and syncope of unexplained origin, there is no consensus on the clinical findings identifying patients with idiopathic dilated cardiomyopathy with an increased risk of sudden cardiac death or malignant ventricular arrhythmias. METHODS: To verify whether electrocardiographic and arrhythmologic features could be useful for prognostic stratification, 78 consecutive patients with an invasive diagnosis of idiopathic dilated cardiomyopathy, but without symptomatic ventricular arrhythmias, were enrolled in a prospective study. Signal-averaged ECG, 24 to 48 hour ECG monitoring and electrophysiologic study were performed at the time of diagnosis to identify arrhythmogenic predictors of outcome. Transplant-free and arrhythmic event-free survival was evaluated on the basis of initial parameters. RESULTS: During a mean follow-up of 85 months, 9 patients died (6 of sudden cardiac death and 3 of congestive heart failure), 10 patients underwent cardiac transplantation for refractory heart failure, and 3 presented with sustained ventricular tachycardia. The independent predictors for death and cardiac transplantation were an HV interval > 55 ms and the combination of frequent repetitive ventricular ectopics with a poor left ventricular function. A strong index of arrhythmic events proved to be the association of a prolonged HV interval with a wide (> 110 ms) QRS complex (odds ratio 4.53, 95% confidence interval 1.57-13.04, p < 0.005). CONCLUSIONS: An accurate measurement of the HV interval and QRS duration at baseline evaluation may add prognostic information in patients with idiopathic dilated cardiomyopathy. In our experience, abnormal values of both parameters identified a group of patients with a very high risk of late occurring arrhythmic events.

Transient platypnea-orthodeoxia-like syndrome induced by propafenone overdose in a young woman with Ebstein's anomaly.

In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.

[Hospital statistics as tool in epidemiologic studies: heart failure in Trieste]. / Le statistiche ospedaliere come strumento di studio epidemiologico: lo scompenso cardiaco a Trieste.

BACKGROUND: Since 1995, the reimbursement of hospital healthcare expenditure in Italy has been based upon the so-called Diagnosis Related Groups (DRGs). The DRG 127 includes all the cases in which the main clinical diagnosis is "heart failure or shock" and, therefore, it may be used to obtain epidemiological data concerning this syndrome. The analysis appears to be of relevance, since in the district of Trieste the phenomenon of progressive aging of the general population has already reached a very advanced phase. METHODS: In this study, we evaluated, using the database of the Sistema Informativo Sanitario Regionale, the epidemiological data and clinical outcome of patients hospitalized for DRG 127 in the district of Trieste from 1997 to 2000 (5514 hospital admissions and 69,236 days of hospital stay). RESULTS: The DRG 127 accounted for 2.6% of the total hospital admissions and 4% of the total days of hospital stay; moreover, it was found to be the first cause of hospitalization for medical DRGs (18.8%) as well as the first cause of hospitalization and of the days of hospital stay for cardiovascular DRGs (27.5 and 40.5%, respectively). Seventy-two percent of patients admitted for DRG 127 were > 75 years. In 1997, a mean of 4/1000 inhabitants of the district of Trieste were hospitalized for DRG 127 (4.6 hospital admissions and 63 days of hospital stay/1000 inhabitants). Over the 4-year period, the number of hospital admissions for DRG 127 increased by 20.4%, the days of hospital stay by 11.1%, and the related healthcare costs rose by 36.7%. Most of the patients (89%) were admitted in Internal Medicine or Geriatric wards. By using suitable corrective factors, the prevalence rate of heart failure in 1997 was estimated at 6.4@1000 (< 65 years 1.8@1000, 65-74 years 10.3@1000, 75-84 years 22.3@1000, > or = 85 years 47.4@1000). On the basis of the first hospital admission, the incidence was estimated at 2.4@1000 (< 65 years 0.8@1000, 65-74 years 2.2@1000, 75-84 years 9.3@1000, > or = 85 years 20.4@1000). The in-hospital 1-, 2- and 3-year survival rates from the time of the first hospital admission for heart failure were, respectively, 92, 80, 68 e 56%. The most frequent etiology was ischemic heart disease (50%), followed by hypertensive (26%) and valvular (7%) heart diseases. Ischemic patients showed the worst prognosis and ischemic heart disease was associated with a 3-year survival rate of 44%. However, the prognosis was found to be significantly influenced by the age of the patients, independently of the disease etiology. CONCLUSIONS: The analysis of the hospitalizations for DRG 127 in the district of Trieste may contribute to forecast the epidemiological scenario and the healthcare demand for heart failure that will occur in the next decades at a national level, and may be useful to plan effective models of integrated home-hospital care for the increasing number of affected subjects.