Giuseppe Di Pasquale

ORIGINAL RESEARCH—ERECTILE DYSFUNCTION: Penile Doppler Ultrasound in Patients with Erectile Dysfunction (ED): Role of Peak Systolic Velocity Measured in the Flaccid State in Predicting Arteriogenic ED and Silent Coronary Artery Disease

INTRODUCTIONnThe use of the penile peak systolic velocity (PSV) measured in the flaccid state during penile color Doppler ultrasound (PCDU) examination has been questioned without substantial evidence.nnnAIMnTo assess the validity of PSV measured in the flaccid state during PCDU, in patients consulting for erectile dysfunction (ED).nnnMETHODSnA consecutive series of 1,346 (mean age 55.0 +/- 12.0 years) male patients was studied.nnnMAIN OUTCOMES MEASURESnAll patients underwent PCDU performed both in the flaccid state and dynamic (after prostaglandin E1 stimulation) conditions. A subset of 20 subjects with uncomplicated type 2 diabetes underwent diagnostic testing for silent coronary heart disease by means of adenosine stress myocardial perfusion scintigraphy (SPECT). In these subjects penile arterial flow was simultaneously assessed by PCDU before and after systemic adenosine administration.nnnRESULTSnFlaccid PSV showed a significant (r = 0.513, P < 0.0001) correlation with dynamic PSV. Receiver operating characteristic (ROC) curve analysis demonstrated that when a threshold of 13 cm/seconds was chosen, flaccid PSV was predictive for dynamic PSV < 25 and <35 cm/seconds with an accuracy of 89% and 82%, respectively. Among the subset of patients who underwent SPECT, an impaired coronary flow reserve (ICFR) occurred in nine cases (45%). When the same threshold of <13 cm/seconds was chosen, PSV before SPECT was predictive of ICFR with an accuracy of 80% (area under the ROC curve = 0.798 +/- 0.10; P < 0.05). After adjustment for confounders, anxiety symptoms were related to dynamic PSV (Adj. r = -0.154, P < 0.05) but not to flaccid PSV.nnnCONCLUSIONSnOur results show that flow in the cavernosal arteries can be routinely evaluated by PCDU in the flaccid state. Performing PCDU only in the flaccid state allows identifying subjects with pathological dynamic PSV with accuracy higher than 80%. Furthermore, our preliminary data suggest that the same examination could identify diabetic subjects with ICFR with an accuracy of 80%.

Rationale and design of the GISSI-Atrial Fibrillation Trial: a randomized, prospective, multicentre study on the use of valsartan, an angiotensin II AT1-receptor blocker, in the prevention of atrial fibrillation recurrence.

Background The possibility of preventing atrial fibrillation recurrence with anti-arrhythmic agents is very limited, given the discouraging results obtained with current drugs in many patients. Data from experimental studies suggest that angiotensin II AT1-receptor blockers can influence atrial remodelling, a key factor in atrial fibrillation initiation and maintenance. Moreover, some preliminary clinical data show that angiotensin II AT1-receptor blockers can prevent atrial fibrillation episodes. The GISSI-Atrial Fibrillation (AF) trial is a randomized, prospective, parallel group, placebo-controlled, multicentre study designed to test whether angiotensin II AT1-receptor blockers can reduce atrial fibrillation recurrence. Objectives and Methods The primary objective of the study is to demonstrate that, in patients with a history of recent atrial fibrillation who are treated with the best recommended therapies, the addition of the angiotensin II AT1-receptor blocker valsartan (titrated up to 320 mg) is superior to placebo in reducing atrial fibrillation recurrence. A substudy will analyse the effect of valsartan on left atrial dimensions and on neurohormones. The study population consists of patients with symptomatic atrial fibrillation (at least two electrocardiogram documented atrial fibrillation episodes in the previous 6 months or successful cardioversion in the last 2 weeks) with underlying cardiovascular diseases or comorbidities. With approximately 100 centres participating in Italy, a total of 1402 patients are randomized in a 1: 1 ratio to receive valsartan or placebo. The enrolment period will last 12 months and the patients will be followed for 12 months from study entry. Conclusions The GISSI-AF is the largest trial aimed at assessing the role of angiotensin receptor blockade in reducing the recurrence of atrial fibrillation and its possible mechanisms of action in terms of its effects on atrium remodelling and neurohormones.

A decade of changes in clinical characteristics and management of elderly patients with non-ST elevation myocardial infarction admitted in Italian cardiac care units.

Objective To describe the evolution of clinical characteristics, in-hospital management and early outcome of elderly patients with non-ST elevation myocardial infarction (NSTEMI). Methods We analysed data from five consecutive Italian nationwide registries, conducted between 2001 and 2010, including patients with acute coronary syndromes admitted to cardiac care units (CCUs). Results Of 10u2005983 patients with NSTEMI enrolled in the 5 surveys, 4350 (39.6%) were ≥75u2005years old (mean age 81±5u2005years). Some clinical characteristics such as diabetes mellitus, hypertension, renal dysfunction and previous percutaneous coronary intervention increased significantly, whereas a history of stroke, myocardial infarction and heart failure decreased over time. An invasive approach increased from 26.6% in 2001 to 68.4% in 2010 (p<0.0001) and revascularisation rates increased from 9.9% to 51.7% (p<0.0001). Early use and prescription at discharge of β-blockers, statins and dual antiplatelet treatment increased significantly (p<0.0001). Thirty-day observed mortality decreased from 14.6% (95% CI 9.9 to 20.4) to 9.5% (95% CI 7.7 to 11.6). At the multivariate logistic regression analyses adjusted for baseline characteristics, compared with 2001, the risk of death was significantly lower in all the other studies performed at different times with reductions in adjusted mortality between 66% and 45%. Conclusions Over the past decade, substantial changes have occurred in the clinical characteristics and management of elderly patients admitted with NSTEMI in Italian CCUs, with a greater use of revascularisation therapy and recommended medications. These variations have been associated with a reduction in 30-day adjusted mortality rate.

Concomitant submassive pulmonary embolism and paradoxical embolic stroke after a long flight: which is the optimal treatment?

Economy class stroke syndrome consists of ischemic stroke due to paradoxical embolism through patent foramen ovale after a long flight. Few cases have been described in the literature to date. The treatment choice could be tricky. We present the case of a 65-year-old woman, admitted for submassive pulmonary embolism after a long flight, that presented a paradoxical embolic stroke through patent foramen ovale shortly after. The patient was treated with intravenous thrombolysis within 1 h of stroke onset with a definite symptoms improvement. Afterwards, intravenous unfractioned heparin was started with strict partial thromboplastin time monitoring. Cerebral computed tomography scan, obtained after 24 and 72 h, ruled out hemorrhage. Warfarin was started after 72 h. Patent foramen ovale was percutaneously closed 3 months after. In the reported case, the treatment with thrombolysis and subsequent heparin infusion was effective and safe. We discuss the rationale for this treatment in the light of literature data.

Does age modify the relationship between adherence to secondary prevention medications and mortality after acute myocardial infarction? A nested case-control study

PurposeClinical trials have shown that evidence-based secondary prevention medications reduce mortality after acute myocardial infarction (AMI). Yet, these medications are generally underused in daily practice, and older people are often excluded from drug trials. The purpose of this study was to examine whether the relationship between adherence to evidence-based drugs and post-AMI mortality varies with increasing age.MethodsThe study population was defined as all residents in the Local Health Authority of Bologna (Italy) hospitalized for AMI between January 1, 2008 and June 30, 2011, and followed up until December 31, 2012. Medication adherence was calculated as the proportion of days covered (PDC) for filled prescriptions of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, antiplatelet drugs, and statins; patients were classified as adherent (PDC ≥75xa0%) or nonadherent (PDC <75xa0%). We used incidence density sampling, and the moderating effect of age on the relationship between adherence and mortality was investigated through conditional multiple logistic regression analysis.ResultsThe study population comprised 3963 patients. During the 5-year study period, 1085 deaths (27.4xa0%) were observed. For both younger and older patients, adherence to polytherapy (three or four medications) was associated with lower mortality (adj. rate ratiou2009=u20090.41; Pu2009<u20090.001). A significant inverse relationship was found between adherence to each of the four medications and mortality, although the risk reduction associated with antiplatelet therapy declined after the age of 70–75.ConclusionsThe beneficial effect of evidence-based polytherapy on mortality following AMI is observed also in older populations. Nevertheless, the risk-benefit ratio associated with antiplatelet therapy is less favorable with increasing age.

Hospital Readmissions of Patients with Heart Failure: The Impact of Hospital and Primary Care Organizational Factors in Northern Italy

Background Primary health care is essential for an appropriate management of heart failure (HF), a disease which is a major clinical and public health issue and a leading cause of hospitalization. The aim of this study was to evaluate the impact of different organizational factors on readmissions of patients with HF. Methods The study population included elderly resident in the Local Health Authority of Bologna (Northern Italy) and discharged with a diagnosis of HF from January to December 2010. Unplanned hospital readmissions were measured in four timeframes: 30 (short-term), 90 (medium-term), 180 (mid-long-term), and 365 days (long-term). Using multivariable multilevel Poisson regression analyses, we investigated the association between readmissions and organizational factors (discharge from a cardiology department, general practitioners’ monodisciplinary organizational arrangement, and implementation of a specific HF care pathway). Results The 1873 study patients had a median age of 83 years (interquartile range 77–87) and 55.5% were females; 52.0% were readmitted to the hospital for any reason after a year, while 20.1% were readmitted for HF. The presence of a HF care pathway was the only factor significantly associated with a lower risk of readmission for HF in the short-, medium-, mid-long- and long-term period (short-term: IRR [incidence rate ratio]=0.57, 95%CI [confidence interval]=0.35–0.92; medium-term: IRR=0.70, 95%CI=0.51–0.96; mid-long-term: IRR=0.79, 95%CI=0.64–0.98; long-term: IRR=0.82, 95%CI=0.67–0.99), and with a lower risk of all-cause readmission in the short-term period (IRR=0.73, 95%CI=0.57–0.94). Conclusion Our study shows that the HF care specific pathway implemented at the primary care level was associated with lower readmission rate for HF in each timeframe, and also with lower readmission rate for all causes in the short-term period. Our results suggest that the engagement of primary care professionals starting from the early post-discharge period may be relevant in the management of patients with HF.

Myocardial rupture with left ventricle to coronary sinus communication: an unusual post-infarction mechanical complication.

We describe a rare case of post-infarction myocardial rupture leading to communication between the left ventricle and coronary sinus, which eventually led to a left-to-right shunt. The observation was made in an elderly woman with subacute infero-posterior myocardial infarction. Diagnosis was initially made by transthoracic echocardiography (elicited by the finding of high-velocity flow within a dilated coronary sinus), and was confirmed in greater detail at cardiac magnetic resonance. This description adds to the list of known post-infarction mechanical complications. The finding of high-velocity flow within the coronary sinus after myocardial infarction suggests the possibility of myocardial rupture leading to left ventricle to coronary sinus communication; an unusual but potentially treatable complication.

The Effect of Age on Characteristics and Mortality of Intracerebral Hemorrhage in the Oldest-Old.

Background: Incidence of acute intracerebral hemorrhage (ICH) increases with age, but there is a lack of information about ICH characteristics in the oldest-old (age ≥85 years). In particular, there is a need for information about hematoma volume, which is included in most clinical scales for prediction of mortality in ICH patients. Many of these scales also assume that, independent of ICH characteristics, the oldest-old have a higher mortality than younger elderly patients (age 65-74 years). However, supporting evidence from cohort studies is limited. We investigated ICH characteristics of oldest-old subjects compared to young (<65 years), young-old (65-74 years) and old-old (75-84 years) subjects. We also investigated whether age is an independent mortality predictor in elderly (age ≥65 years) subjects with acute ICH. Methods: We retrospectively collected clinical and neuroimaging data of 383 subjects (age 34-104 years) with acute supratentorial primary ICH who were admitted to an Italian Stroke Unit (SU) between October 2007 and December 2014. Measured ICH characteristics included hematoma location, volume and intraventricular extension of hemorrhage on admission CT scan; admission Glasgow Coma Scale ≤8 and hematoma expansion (HE) measured on follow-up CT-scans obtained after 24 h. General linear models and logistic models were used to investigate the association of age with ICH characteristics. These models were adjusted for pre-admission characteristics, hematoma location and time from symptom onset to admission CT scan. Limited to elderly subjects, Cox models were used to investigate the association of age with in-SU and 1-year mortality: the model for in-SU mortality adjusted for pre-admission and ICH admission characteristics and the model for 1-year mortality additionally adjusted for functional status and disposition at SU discharge. Results: Independent of pre-admission characteristics, hematoma location and time from symptom onset to admission CT-scan, oldest-old subjects had the highest admission hematoma volume (p < 0.01). Age was unrelated to all other ICH characteristics including HE. In elderly patients, multivariable adjusted risk of in-SU and 1-year mortality did not vary across age categories. Conclusions: Oldest-old subjects with acute supratentorial ICH have higher admission hematoma volume than young and young-old subjects but do not differ for other ICH characteristics. When taking into account confounding from ICH characteristics, risk of in-SU and 1-year mortality in elderly subjects with acute supratentorial ICH does not differ across age categories. Our findings question use of age as an independent criterion for stratification of mortality risk in elderly subjects with acute ICH.

Mortality After Admission to Stroke Unit for Intracerebral Hemorrhage: Effect of Age 80 and Older and Multimorbidity

To the Editor: The incidence of spontaneous intracerebral hemorrhage (ICH) increases exponentially with age, so individuals aged 80 and older are expected to represent a growing proportion of all people admitted to stroke units (SU) for ICH. Age of 80 and older is considered to be a major predictor of ICH mortality independent of characteristics related to ICH severity, but supporting evidence is limited to two small noncontemporary cohort studies and a large contemporary cohort study that did not control for any confounders. Findings from noncontemporary cohorts may not be applicable to individuals with ICH currently benefiting from organized inpatient (SU) care, which has improved ICH survival. Another limitation of these studies is the lack of control for prestroke multimorbidity, which is a known predictor of mortality in stroke. This prospective study investigated whether, in individuals with ICH admitted to a SU, age of 80 and older predicts in-SU mortality independent of multimorbidity. The study included 213 participants aged 80 and older (mean age 84.9 4.0, 57.9% male) and 259 participants younger than 80 (mean age 68.7 9.9, 39.9% male) with spontaneous first-episode ICH consecutively admitted to the SU of the Maggiore Hospital (Bologna, Italy) between October 2007 and December 2013. The Maggiore Hospital ethics committee approved the study. All participants (or their representatives) provided informed consent. Information was collected from medical records. Multimorbidity was defined as a Charlson Comorbidity Index of 2 or greater. Other confounders were sex, hypertension, diabetes mellitus, atrial fibrillation, dementia, prestroke functional impairment (modified Rankin Scale), neurological impairment on admission (National Institutes of Health Stroke Scale), anticoagulation-related etiology, pulse pressure, neuroradiological findings (location and intraventricular extension), and recourse to neurosurgical procedures. The association between aged 80 and older and in-SU mortality was estimated using hazard ratios (HRs) and their 95% confidence intervals (CIs) from Cox proportional hazards regression models adjusted for prestroke and ICH-related confounders. Preliminary analyses showed a significant interaction between age and multimorbidity (P = .04). Based on inspection of survival curves and on previous literature, the interaction was modeled as a time-dependent variable to obtain separate mortality risk estimates for stays or 7 or fewer days and longer than 7 days. Analyses were performed using SPSS version 21 (IBM Corp., Armonk, NY). P < .05 was considered statistically significant. Mortality at 7 days or fewer (69.3% of all deaths) was unrelated to age or multimorbidity (Table 1). By contrast, mortality at longer than 7 days was six times as high for younger than 80 with multimorbidity and aged 80 and older with and without multimorbidity than for younger than 80 without multimorbidity. In individuals with stroke, deaths within the first week are mostly the direct consequence of hemorrhagic injury, whereas deaths in the following weeks are mostly related to medical complications. Therefore, age 80 and older and multimorbidity may fail to affect in-SU mortality during the first week because, at this time, prognosis mainly depends on ICH severity, but after the first week, age 80 and older and multimorbidity may become relevant for managing medical complications. Nevertheless, in the model, the effect of multimorbidity was limited to individuals younger than 80. It may be that, in individuals aged 80 and older, the direct consequences of hemorrhagic injury override those of medical complications for a longer time than in younger individuals. Age-related alterations in cellular architecture and the metabolism of the human brain that may aggravate hematoma expansion and perihematomal edema are consistent with this hypothesis. Moreover, animal models show that brain hemorrhage in older age is associated with excess

Risk-adjustment models for heart failure patients' 30-day mortality and readmission rates: the incremental value of clinical data abstracted from medical charts beyond hospital discharge record

BackgroundHospital discharge records (HDRs) are routinely used to assess outcomes of care and to compare hospital performance for heart failure. The advantages of using clinical data from medical charts to improve risk-adjustment models remain controversial. The aim of the present study was to evaluate the additional contribution of clinical variables to HDR-based 30-day mortality and readmission models in patients with heart failure.MethodsThis retrospective observational study included all patients residing in the Local Healthcare Authority of Bologna (about 1 million inhabitants) who were discharged in 2012 from one of three hospitals in the area with a diagnosis of heart failure. For each study outcome, we compared the discrimination of the two risk-adjustment models (i.e., HDR-only model and HDR-clinical model) through the area under the ROC curve (AUC).ResultsA total of 1145 and 1025 patients were included in the mortality and readmission analyses, respectively. Adding clinical data significantly improved the discrimination of the mortality model (AUCu2009=u20090.84 vs. 0.73, pu2009<u20090.001), but not the discrimination of the readmission model (AUCu2009=u20090.65 vs. 0.63, pu2009=u20090.08).ConclusionsWe identified clinical variables that significantly improved the discrimination of the HDR-only model for 30-day mortality following heart failure. By contrast, clinical variables made little contribution to the discrimination of the HDR-only model for 30-day readmission.