Pasquale Caldarola

Feasibility and effectiveness of a disease and care management model in the primary health care system for patients with heart failure and diabetes (Project Leonardo)

Purpose Project Leonardo represented a feasibility study to evaluate the impact of a disease and care management (D&CM) model and of the introduction of “care manager” nurses, trained in this specialized role, into the primary health care system. Patients and methods Thirty care managers were placed into the offices of 83 general practitioners and family physicians in the Apulia Region of Italy with the purpose of creating a strong cooperative and collaborative “team” consisting of physicians, care managers, specialists, and patients. The central aim of the health team collaboration was to empower 1,160 patients living with cardiovascular disease (CVD), diabetes, heart failure, and/or at risk of cardiovascular disease (CVD risk) to take a more active role in their health. With the support of dedicated software for data collection and care management decision making, Project Leonardo implemented guidelines and recommendations for each condition aimed to improve patient health outcomes and promote appropriate resource utilization. Results Results show that Leonardo was feasible and highly effective in increasing patient health knowledge, self-management skills, and readiness to make changes in health behaviors. Patient skill-building and ongoing monitoring by the health care team of diagnostic tests and services as well as treatment paths helped promote confidence and enhance safety of chronic patient management at home. Conclusion Physicians, care managers, and patients showed unanimous agreement regarding the positive impact on patient health and self-management, and attributed the outcomes to the strong “partnership” between the care manager and the patient and the collaboration between the physician and the care manager. Future studies should consider the possibility of incorporating a patient empowerment model which considers the patient as the most important member of the health team and care managers as key health care collaborators able to enhance and support services to patients provided by physicians in the primary health care system.

Increased carotid IMT in overweight and obese women affected by Hashimoto's thyroiditis: an adiposity and autoimmune linkage?

BackgroundHashimotos thyroiditis is the most important cause of hypothyroidism. It is a systemic disease that can even affect the cardiovascular system, by accelerating the atherosclerotic process. Aim of this study was to examine whether autoimmune thyroiditis has an effect on the intima-media thickness of the common carotid artery (IMT-CCT), independently of the thyroid function and well-known cardiovascular risk factors. Hashimotos thyroiditis is a systemic disease. The aim is to examine whether autoimmune thyroiditis and adiposity can effect carotid IMT independently of thyroid hormones and cardiovascular risk factors.MethodsA total of 104 obese women (BMI ≥ 25.0 kg/m-2), with FT3 and FT4 serum levels in the normal range and TSH levels < 4.5 μU/ml, were investigated. None of these patients was taking any kind of drug influencing thyroid function. Measurements were made of the IMT-CCT, BMI, waist circumference, blood pressure levels, as well as fasting TSH, FT3, FT4, anti-thyroid antibodies, insulin, fasting glycemia, triglycerides, total and HDL-cholesterol serum concentrations.ResultsOf the 104 women, 30 (28.8%) were affected by autoimmune thyroiditis. Significantly higher values of IMT-CCT (p < 0.05), TSH (p < 0.05), and triglycerides (p < 0.05) were obtained, and significantly lower values of FT4 (p < 0.05), in patients with Hashimotos thyroiditis as compared to those with a normal thyroid function. When examining the whole group together, at multiple regression analysis Hashimotos thyroiditis maintained a positive association with the IMT (p < 0.001), independently of age, hypertension, BMI, and the fasting serum levels of TSH, FT3, FT4, insulin, fasting glycemia, triglycerides, total and HDL-cholesterol levels.ConclusionsThe present study shows that Hashimotos thyroiditis is associated to an increased IMT only in overweight and obese, independently of the thyroid function, BMI and cardiovascular risk factors. These results suggest that Hashimotos thyroiditis is a marker of evolution of the atherosclerosis if combined to adiposity.

Renal impairment and outcome in patients with takotsubo cardiomyopathy

OBJECTIVES The objectives were to ascertain the prevalence of renal impairment among patients with a takotsubo cardiomyopathy (TTC) episode and whether clinical outcomes are related to renal function. METHODS A total of 108 consecutive subjects with TTC were enrolled in a multicenter registry and followed for a mean period of 429 days. Renal function was evaluated during hospitalization in terms of acute kidney injury/failure and estimated glomerular filtration rate (eGFR). Incidence of death, rehospitalization, and recurrence of TTC during follow-up was recorded. RESULTS Raised creatinine levels can be found during hospitalizations for TTC episodes (analysis of variance P<.001). Incidence of acute kidney injury was 10%; that of acute kidney failure was 1%. Admission eGFR levels were proportional to the duration of hospitalization (r = -0.28, P<.01). Estimated GFR nadir values were related to adverse events at follow-up (log-rank P<.001). The hazard ratio of adverse events at follow-up in subjects with severe renal impairment (nadir eGFR <30 mL/[min 1.73 m(2)]) vs those with eGFR >60 mL/(min 1.73 m(2)) was 1.817 (95% confidence interval, 1.097-3.009; P<.05). CONCLUSIONS Raised creatinine levels and impaired renal function may be found in patients with TTC. Lower eGFR values during hospitalization are associated with longer hospitalizations and higher rates of adverse events at follow-up. Renal function during a TTC episode should be carefully evaluated.

Pre-hospital electrocardiogram triage with tele-cardiology support is associated with shorter time-to-balloon and higher rates of timely reperfusion even in rural areas: data from the Bari- Barletta/Andria/Trani public emergency medical service 118 registry on primary angioplasty in ST-elevation myocardial infarction

Background: We report the preliminary data from a regional registry on ST-elevation myocardial infarction (STEMI) patients treated with primary angioplasty in Apulia, Italy; the region is covered by a single public health-care service, a single public emergency medical service (EMS), and a single tele-medicine service provider. Methods: Two hundred and ninety-seven consecutive patients with STEMI transferred by regional free public EMS 1-1-8 for primary-PCI were enrolled in the study; 123 underwent pre-hospital electrocardiograms (ECGs) triage by tele-cardiology support and directly referred for primary-PCI, those remaining were just transferred by 1-1-8 ambulances for primary percutaneous coronary intervention (PCI) (diagnosis not based on tele-medicine ECG; already hospitalised patients, emergency-room without tele-medicine support). Time from first ECG diagnostic for STEMI to balloon was recorded; a time-to-balloon <1 h was considered as optimal and patients as timely treated. Results: Mean time-to-balloon with pre-hospital triage and tele-cardiology ECG was significantly shorter (0:41±0:17 vs 1:34±1:11 h, p<0.001, –0:53 h, –56%) and rates of patients timely treated higher (85% vs 35%, p<0.001, +141%), both in patients from the ‘inner’ zone closer to PCI catheterisation laboratories (0:34±0:13 vs 0:54±0:30 h, p<0.001; 96% vs 77%, p<0.01, +30%) and in the ‘outer’ zone (0:52±0:17 vs 1:41±1:14 h, p<0.001; 69% vs 29%, p<0.001, +138%). Results remained significant even after multivariable analysis (odds ratio for time-to-balloon 0.71, 95% confidence interval (CI) 0.63–0.80, p<0.001; 1.39, 95% CI 1.25–1.55, p<0.001, for timely primary-PCI). Conclusions: Pre-hospital triage with tele-cardiology ECG in an EMS registry from an area with more than one and a half million inhabitants was associated with shorter time-to-balloon and higher rates of timely treated patients, even in ‘rural’ areas.

Ivabradine, coronary artery disease, and heart failure: beyond rhythm control

Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies.

Management of patients with acute coronary syndromes in real-world practice in Italy: an outcome research study focused on the use of ANTithRombotic Agents: the MANTRA registry

Background: Although outcomes of acute coronary syndromes (ACS) have greatly improved, bleeding is still an issue. Thus, this study aims to evaluate in-hospital management and outcomes of unselected patients with ACS focusing on antithrombotic therapies and bleeding. Methods and results: From 22 April 2009 to 29 December 2010, 6394 consecutive Italian patients were prospectively enrolled and followed for 6 months. Most patients (55.3%) had non-ST-elevation (NSTE) ACS. Of the ST-elevation (STE) ACS patients, 79.8% received reperfusion (mainly mechanical). In-hospital and 6-month unadjusted total mortality rates were 4.2 and 7.8% for STE-ACS and 2.5 and 6.4% for NSTE-ACS, respectively. During hospitalization, TIMI major bleeding rate was 1.2% (1.4% STE-ACS and 1.1% NSTE-ACS, respectively) and TIMI minor bleeding was 3.1%. In-hospital and 6-month unadjusted total mortality rates were 3.1 and 6.7% for patients without bleeding, 1.5 and 8.6% for minor bleeding, and 19.0 and 26.6% for TIMI major bleeding, respectively (p<0.0001). Notably, TIMI major bleeding was one of the strongest predictors of the 6-month composite end point (death or reinfarction) (STE-ACS hazard ratio, HR, 2.86, 95% confidence interval, 95% CI, 1.57−5.23; NSTE-ACS HR, 2.71, 95% CI 1.52−4.80). Predictors of in-hospital TIMI major bleeding were weight (odds ratio, OR, 0.97, 95% CI 0.95−0.99), female gender (OR 1.80, 95% CI 1.09−2.96), history of peripheral vasculopathy (OR 2.95, 95% CI 1.83−4.78), switching anticoagulant therapy (OR 2.62, 95% CI 1.36−5.05), intra-aortic balloon pump implantation (OR 4.44, 95% CI 1.85−10.69), and creatinine ≥2 mg/dl on admission (OR 3.68, 95% CI 1.84−7.33). Conclusions: Despite aggressive management, the rate of bleeding remains relatively low in an unselected ACS population. However, major bleeding adversely affects prognosis and physicians should tailor treatments to reduce it.

Direct oral anti-coagulants compared with vitamin-K inhibitors and low-molecular-weight-heparin for the prevention of venous thromboembolism in patients with cancer: A meta-analysis study

BACKGROUND Prior meta-analysis studies showed that direct oral anticoagulants (DOAs) are as effective and safe as warfarin for the prevention of recurrences in patients with venous thrombo-embolism(VTE) and cancer. However, randomized studies also showed that low-molecular-weight-heparin (LMWH) performs better than warfarin in subjects with cancer. We therefore aimed to assess whether, even after pooling data with warfarin and LMWH, the use of DOAs remains safe and effective. METHODS We performed a meta-analysis of randomized controlled trials with the aim of assessing the efficacy and safety of DOAs in patients with VTE and cancer. Data on recurrent VTE and major and clinically relevant nonmajor bleeding were analyzed. Data were pooled and compared by ORs and 95% CIs. RESULTS Nine studies were included in the meta-analysis, seven in comparison with VKI, 2 with LMWH, accounting for a total of 1952 patients. VTE recurred in 5.4% and in 5.9% of patients with cancer treated with DOAs and conventional treatment, respectively (OR 0.79; 95% CI, 0.53-1.17; I2 0%). Bleeding occurred in 10.8% and 11% of patients receiving DOAs and conventional treatment, respectively (OR 0.96; 95% CI, 0.71-1.30; I2, 44%). Higher bleeding rates were found when DOAs are compared with LMWH (OR 2.72, 95% CI, 1.05-7.01). CONCLUSIONS DOAs seem to be as effective and safe as conventional treatment for the prevention of VTE in patients with cancer in comparison with VKI. Higher bleeding rates were found when DOAs are compared with LMWH.

Statin therapy in heart failure: for good, for bad, or indifferent?

Statins are effective in the prevention of coronary events and the treatment of acute coronary syndromes. However, their efficacy and safety in patients with heart failure (HF) is still a matter of debate. On the basis of literature evidence from subgroup analysis, retrospective, prospective cohort studies, and randomized controlled trials, in this review we try to answer the following question: Is statin therapy in HF patients for good, for bad, or indifferent? Some studies showed a negative impact of low cholesterol levels in patients with severe HF (endotoxin–lipoprotein hypothesis and coenzyme Q10 hypothesis). On the other hand, a large amount of literature demonstrates that in patients with HF, statins have a positive impact on survival and other outcomes, regardless of whether the HF was of ischemic or nonischemic origin, which is related to a combination of mechanisms (pleiotropic effects and cholesterol reduction). Much of this evidence, however, comes from observational and retrospective studies and subgroup analyses of statin use in patients with HF. Randomized clinical trials examining the efficacy of statins in HF (GISSI-HF and CORONA) did not show a benefit in mortality for patients with HF randomized to receive statins. Nevertheless, a meta-analysis found that statin therapy does not decrease all-cause or cardiovascular mortality but significantly decreases the rate of hospitalization for worsening HF and increased left ventricular ejection fraction compared with placebo.

Galectin-3 Serum Levels Are Independently Associated With Microalbuminuria in Chronic Heart Failure Outpatients

Background: Galectin-3 (Gal-3) is a novel biomarker reflecting inflammation status and fibrosis involving worsening of both cardiac and renal functions. Objectives: The aim of this study was to evaluate the relationship between Gal-3 serum levels and microalbuminuria in a group of chronic heart failure (CHF) outpatients. Patients and Methods: We enrolled CHF outpatients having stable clinical conditions and receiving conventional therapy. All patients underwent clinical evaluation, routine chemistry analysis, echocardiography, and evaluation of the urinary albumin/creatinine ratio (UACR). Results: Among the patients enrolled, 61 had microalbuminuria (UACR, 30-299) and 133 normoalbuminuria (UACR, < 30). Patients with normoalbuminuria showed significantly higher levels of Gal-3 than those without (19.9 ± 8.8 vs. 14.6 ± 5.5 ng/mL). The stepwise regression analysis indicated that Gal-3 was the first determinant of microalbuminuria (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.02 - 1.14, P = 0.012), followed by diabetes (OR 2.14; 95% CI: 1.00 - 4.57; P = 0.049) and high central venous pressure (OR 2.80; 95% CI: 1.04 - 7.58; P= 0.042). Conclusions: Our findings indicate an independent association between Gal-3 levels and microalbuminuria, an early marker of altered renal function. This suggests the possible role of Gal-3 in the progression of cardiorenal syndrome in CHF outpatients.

Prevalence and Prognostic Impact of Diabetes in Takotsubo Syndrome: Insights From the International, Multicenter GEIST Registry

OBJECTIVE In view of low prevalence rates, diabetes is discussed as a protective factor for the occurrence of Takotsubo syndrome (TTS). Furthermore, it was associated with improved outcome in a small single-center analysis. Therefore, this study assessed the prevalence and prognostic relevance of concomitant diabetes in TTS. RESEARCH DESIGN AND METHODS A total of 826 patients with TTS were enrolled in an international, multicenter, registry-based study (eight centers in Italy and Germany). All-cause mortality was compared between patients with diabetes and patients without diabetes, and the independent predictive value of diabetes was evaluated in multivariate regression analysis. RESULTS The prevalence of diabetes was 21.1% (n = 174). TTS patients with diabetes were older (P < 0.001), were more frequently male (P = 0.003), had a higher prevalence of hypertension (P < 0.001), physical triggers (P = 0.041), and typical apical ballooning (P = 0.010), had a lower left ventricular ejection fraction (P = 0.008), had a higher rate of pulmonary edema (P = 0.032), and had a longer hospital stay (P = 0.009). However, 28-day all-cause mortality did not differ between patients with diabetes and patients without diabetes (6.4% vs. 5.7%; hazard ratio [HR] 1.11 [95% CI 0.55–2.25]; P = 0.772). Longer-term follow-up after a median of 2.5 years revealed a significantly higher mortality among TTS patients with diabetes (31.4% vs. 16.5%; P < 0.001), and multivariate regression analysis identified diabetes as an independent predictor of adverse outcome (HR 1.66 [95% CI 1.16–2.39]; P = 0.006). CONCLUSIONS Diabetes is not uncommon in patients with TTS, is associated with increased longer-term mortality rates, and is an independent predictor of adverse outcome irrespective of additional risk factors.