Combined Effects of Age and Comorbidities on Electrocardiographic Parameters in a Large Non-Selected Population.

Background: Previous studies have evaluated average electrocardiographic (ECG) values in healthy subjects or specific subpopulations. However, none have evaluated ECG average values in not selected populations, so we examined ECG changes with respect to age and sex in a large primary population. Methods: From digitized ECG stored from 2008 to 2021 in the Modena province, 130,471 patients were enrolled. Heart rate, P, QRS and T wave axis, P, QRS and T wave duration, PR interval, QTc, and frontal QRS-T angle were evaluated. Results: All ECG parameters showed a dependence on age, but only some of them with a straight-line correlation: QRS axis (p < 0.001, R2 = 0.991, r = 0.996), PR interval (p < 0.001, R2 = 0.978, r = 0.989), QTc (p < 0.001, R2 = 0.935, r = 0.967), and, in over 51.5 years old, QRS-T angle (p < 0.001, R2 = 0.979, r = 0.956). Differences between females and males and in different clinical settings were observed. Conclusions: ECG changes with ageing are explainable by intrinsic modifications of the heart and thorax and with the appearance of cardiovascular diseases and comorbidities. Age-related reference values were computed and applicable in clinical practice. Significant deviations from mean values and from Z-scores should be investigated.

The Prognostic Importance of TAPSE in Early and in Stable Cardiovascular Diseases.

The identification of predictors of major cardiovascular events (MACES) represents a big challenge, especially in early and stable cardiovascular diseases. This prospective study comparatively evaluated the prognostic importance of left ventricular (LV) and right ventricular (RV) systolic and diastolic function, pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) in a stable patient's cohort with cardiovascular risk factors. The LV ejection fraction, mitral annular plane systolic excursion (MAPSE), tricuspid annular plane systolic excursion (TAPSE), functional mitral regurgitation (FMR), doppler tissue imaging of mitral and tricuspid annulus with systolic and diastolic peaks estimation, tricuspid regurgitation velocity (TRV), pulmonary velocity outflow time integral (PVTI), mean pulmonary artery pressure (MPAP) and PVR were estimated at enrollment. During the follow-up, MACES and all-cause mortality were recorded. 369 subjects with or without previous MACES were enrolled. Bivariate analysis revealed LVEF, TAPSE, MPAP, TRV, PVR, LV diastolic function, and FMR were associated with the endpoints. When computing the influence of covariates to the primary endpoint (all-cause mortality and MACES) through Cox analysis, only LV diastolic function and TAPSE entered the final model; for the secondary endpoint (MACES) only TAPSE entered. TAPSE was able to predict MACES and all-cause mortality in early and stable cardiovascular diseases. The use of TAPSE should be implemented.

Cell therapy and left ventricular restoration for ischemic cardiomyopathy: long-term results of a perspective, randomized study.

BACKGROUND: Aim of this study is to verify the potential advantages and benefits of bone-marrow derived autologous stem cells implantation associated to surgical left ventricular restoration (SVR), to report a new modality of cell delivery to myocardium, and to identify possible side effects of this procedure. METHODS: Between March 2007 and March 2013, 30 patients affected by ischemic dilative cardiomyopathy who received a SVR operation were enrolled in the study. The population was divided in two groups:16 patients were randomly assigned to receive stem cells therapy in addition to SVR (groupA), 14 patients received a placebo (group B). The two groups were homogeneous in respect of age, gender, preoperative NYHA class, mitral incompetence and left ventricular sizes and volumes. The patients were evaluated by echo and pet-scan before surgery and at 6 months follow-up, and by echo at subsequent follow-up. RESULTS: Overall 30 days-in hospital mortality was 0 for the entire cohort. At last follow-up ejection fraction increased from 25.3% before surgery to 36.3% in group A, and from 31.8% to 45.6% in group B. Reduction of LVEDD was 6% in group A, 9% in group B. ESLVV and EDLVD decreased more significantly in patients receiving stem cells (55% vs. 35%). Late cardiac mortality at 9 years follow-up was similar in the two groups of patients. No early or late adverse reaction nor cases of infections were observed. CONCLUSIONS: Patients affected by ischemic cardiomyopathy have a favourable outcome after SVR. A higher reduction of LVEDV and LVESV assessed by CT-Scan evaluation in patients receiving cell therapy, when compared to control group, encourages the evolution and refinement of myocardial regenerative therapy added to SVR.

Effects of Cholecalciferol Supplementation in Patients with stable heart failure and LOw vITamin D levels (ECSPLOIT-D): a double-blind, randomized, placebo-controlled pilot study.

BACKGROUND: The aim of this study was to investigate the effects of vitamin D (VD) on the interaction among functional, echocardiographic and hormonal parameters in patients with heart failure (HF) and VD deficiency. METHODS: In a randomized, double blind trial, 35 patients with HF and VD<20 ng/mL, received either 300,000 U of oral cholecalciferol followed by 50,000 U/month for 6 months, or placebo treatment. RESULTS: Changes in the 6 Minute Walking Test (6MWT) assessed at 3 and 6 months in treatment group was the primary end point. Secondary endpoints were echocardiographic and hormonal changes. The same targets were compared in treated and placebo groups as secondary endpoints. In the treatment group the 6MWT improved at 3 (from 210±104 mt to 225±94 mt; P=0.033) but not at 6 months (from 210±104 mt to 217±94 mt; P=0.288) while PTH dropped at 3 (from 76.8±50.5 to 50.2±20.3 pg/mL; P=0.025), but not at 6 months. 6MWT improvement was negatively related to baseline VD levels. Variation in 6MWT did not significantly differ among groups at 3 (13.6±23.3 vs. 3.6±17.3; P 0.175) and 6 months (12.1±31.4 vs. 0.2±23.2; P 0.225). Left atrial size increased in the placebo group (from 50.8±20.7 to 61.7±36.0 mL/m2; P=0.010). Other hormonal parameters remained unchanged. CONCLUSIONS: In summary, the treatment of VD deficiency in patients with HF improved 6MWT after 3 months along with a decrease in PTH levels. However when compared with the placebo arm, treatment of VD deficiency did not influence the final outcomes.

Right ventricular presystolic peak velocity represents right ventricular function in stable patients.

BACKGROUND: Right ventricular (RV) function is difficult to be measured but plays a role in morbility and mortality of patients with cardiopulmonary diseases, so many echocardiographic parameters have been developed from M-mode, B-mode and Doppler tissue imaging (DTI) evaluation. Right ventricular presystolic peak velocity (RVPrP) measured with DTI of the tricuspidal annulus and its changes in RV dysfunction have never been assessed in a patient's cohort of stable patients with cardiovascular risk factors. RVPrP velocity could have a role in RV function evaluation; this study addresses such issue. METHODS: Four hundred thirty-six consecutive patients were submitted to a complete echocardiographic examination with the contemporary evaluation of the following RV function indexes: Tricuspid Annulus Plane Systolic Excurtion (TAPSE), RV Systolic Peak (RVSyP) and RVPrP. Pulmonary artery systolic pressure (PASP), left ventricular and RV diastolic function were also evaluated. RESULTS: According to TAPSE and RVSyP taken alone or in combination, 113 patients had RV dysfunction, while 323 patients had normal RV function. RVPrP was reduced in patient's group with RV dysfunction with respect to patient's group with preserved RV function (16.48±7.3 cm/s vs. 23.98±8.4 cm/s, respectively, P<0.001). RVPrP was related with RVSyP (P<0.001) and with TAPSE (P=0.002). TAPSE and RVSyP revealed a poor concordance to define RV dysfunction. PASP was higher in patient's group with reduced RV function (P=0.033). CONCLUSIONS: The study showed RVPrP able to detect stable patients with RV dysfunction.

Does coronary Atherosclerosis Deserve to be Diagnosed earlY in Diabetic patients? The DADDY-D trial. Screening diabetic patients for unknown coronary disease.

OBJECTIVES: To evaluate if screening and treatment of asymptomatic coronary artery disease (CAD) are effective in preventing first cardiac event in diabetics. METHODS: Diabetic patients without known CAD were randomly assigned to undergo a screening for silent myocardial ischemia followed by revascularization or to continue follow-up. The reduction of cardiac death (CD) or nonfatal myocardial infarction (MI) represented the primary aim; secondary aim was the prevention of heart failure (HF). RESULTS: From September 2007 to May 2012, 520 patients (62 years; 104 female) were enrolled. Silent CAD was found in 20 of 262 patients (7.6%), revascularization was performed in 12 (4.6%). After a mean follow-up of 3.6 years 12 events (4.6%) occurred in the study group and 14 (5.4%) in the follow-up (HR=0.849, 95% CI: 0.393-1.827, P=0.678). The occurrence of first HF episode did not differ between groups: 2 (0.8%) in screened and 7 (2.7%) in follow-up (HR=0.273, 95% CI: 0.057-1.314, P=0.083). Subgroup analysis revealed a significantly lower HF episodes among patients with intermediate cardiovascular risk (Log rank P=0.022). Additionally, when CD and MI were analysed within subgroups, a significant lower number of CDs was observed among older than 60 years (P=0.044). CONCLUSION: Screening and revascularization of silent CAD in diabetics, failed to demonstrate a significant reduction in cardiac events and HF episodes. However, our data indicate that further research is warranted in patients older than 60 years and those with an intermediate cardiovascular risk. CLINICALTRIALS.GOV: NCT00547872.

Meal-induced blood pressure variation and cardiovascular mortality in ambulatory hypertensive elderly patients: preliminary results.

OBJECTIVES: This prospective cohort study was designed to investigate the prevalence and the prognostic value of postprandial hypotension (PPH) in ambulatory hypertensive elderly patients without overt heart diseases, an issue that has never been evaluated so far. METHODS: All patients consecutively referred to our cardiologic clinic in the period from January 2005 to August 2009, were enrolled in the study and underwent a 24-h ambulatory arterial blood pressure monitoring (ABPM). PPH has been defined as a decrease in SBP of 20  mmHg within 2  h after a meal. RESULTS: Four hundred and one patients were enrolled (mean age 77.7  ±  11 years, males 47.7%). Hypertension was not adequately controlled in 290 (72.3%) patients. PPH was found in 292 of 401 (72.8%) patients. A value of 10  mmHg or higher of SD SBP was predictive of PPH, with a sensitivity and specificity of 87 and 57%, respectively. At each meal, patients with higher SBP readings before meal had the greatest decrease in SBP (P  <  0.001). During the follow-up, 34 patients died for cardiovascular causes. Breakfast BP variation was the most predictive variable of cardiovascular mortality (B  =  0.020, P  =  0.04, HR 1.020, IC 1.001-1.040). CONCLUSION: In our population, PPH was common. A diurnal standard deviation of SBP of 10  mmHg or higher was suggestive of its presence. ABPM identified breakfast BP decrease as a possible new risk factor for cardiovascular mortality.

Right ventricular function predicts cardiovascular events in outpatients with stable cardiovascular diseases: preliminary results.

Right ventricular (RV) function impacts the outcome in cardiac and pulmonary diseases such as heart failure, pulmonary hypertension, myocardial infarction, valvular, and congenital heart diseases. To our knowledge, simultaneous evaluation of left ventricular (LV) and RV systolic and diastolic echocardiographic indices in outpatients with clinically stable cardiovascular diseases has never been performed. Thus, we designed a prospective cohort study to define the prognostic power of these parameters. One hundred and sixty-three patients were submitted to transthoracic echocardiography with multiparametric and tissue Doppler evaluation of the following indices: ejection fraction, MAPSE, TAPSE, RV presystolic peak, LV and RV diastolic function, pulmonary artery systolic pressure, and functional mitral regurgitation. All these parameters and clinical variables (age, sex, and prior cardiovascular events) were entered in a multivariable Cox regression model. The primary end point was the occurrence of major cardiovascular events (MACEs) during the follow-up period. Twenty-one MACEs were observed; in the final multivariable Cox regression model only prior cardiovascular events (B 1.305, p 0.004, 95% CI 1.523-8.933), age (B 0.067, p 0.005, 95% CI 1.020-1.121), and TAPSE (B -1.065, p 0.026, 95% CI 0.135-0.883) were associated with MACEs. TAPSE, a simple and reproducible echocardiographic index, may be viewed as an early echocardiographic marker of heart involvement in atherosclerosis. We believe that TAPSE may be useful in clinical practice for risk stratification.

Screening asymptomatic patients with diabetes for unknown coronary artery disease: does it reduce risk? An open-label randomized trial comparing a strategy based on exercise testing aimed at revascularization with management based on pharmacological/behavioural treatment of traditional risk factors. DADDY-D Trial (Does coronary Atherosclerosis Deserve to be Diagnosed and treated early in Diabetics?).

BACKGROUND: Coronary artery disease is the leading cause of morbidity and mortality in patients with type 2 diabetes. Screening for asymptomatic coronary artery disease with treatment by means of revascularization seems to be an appealing option for prevention. The utility of such a strategy has never been challenged in a randomized trial. METHODS/DESIGN: In the present study a cohort of diabetic patients without any symptoms and without known coronary artery disease will be screened at two diabetes outpatients services. Those with intermediate or high risk (equal or greater than 10% according to the Italian risk chart) will be asked to participate and enrolled. They will be seen and followed in order to provide the best adherence to medical therapy. Half of the patients will be randomized to undergo an exercise tolerance testing while the other group will continue to be regularly seen at diabetes outpatients services. Best medical/behavioral therapy will be offered to both groups. Those patients with a positive exercise tolerance testing will be studied by coronary angiography and treated according to the severity of coronary lesions by percutaneous stenting or surgery.The objective of the study is to evaluate the efficacy of the screening strategy aimed at revascularization. A cost-effectiveness analysis will be performed at the end of the follow up. DISCUSSION: The study will provide useful information about prevention and treatment of diabetic patients at high risk of coronary events. It will be made clearer if detection of silent coronary artery disease has to be recommended and followed by treatment. Given the simplicity of the study protocol, it will be easily transferable to the real world. TRIAL REGISTRATION: (ClinicalTrials.gov): NCT00547872.

Systolic and diastolic functions in elderly patients with and without heart failure.

BACKGROUND: A considerable number of patients with heart failure (HF) have a normal left ventricular ejection fraction (LVEF). In these subjects, HF has usually been related to diastolic heart failure (DHF), still a frequently overlooked clinical entity. METHODS: This study reports the clinical, instrumental, and conventional echocardiographic evaluation of 159 consecutive, hospitalized elderly patients, 87 admitted with HF and 72 admitted for other reasons without overt HF. RESULTS: All of the 87 HF patients had signs of diastolic dysfunction (DDYS), yet 44.8% of them had a normal LVEF. Forty-four of the 72 patients admitted without overt HF (61.1%) had mild DDYS and 14 (19.5%) also had a reduced LVEF. There was a clear relationship between LVEF reduction and the severity of DDYS. CONCLUSIONS: HF is often a combination of diastolic and systolic function abnormalities. DHF may be difficult to detect in HF subjects with normal LVEF because their DDYS is often mild. However, there are signs of DDYS in all HF patients that increase in severity as LVEF decreases. DDYS could be considered a marker for all forms of HF, especially in elderly patients.

Massive bone marrow crystal-storing histiocytosis in a patient with IgA-lambda multiple myeloma and extensive extramedullary disease. A case report.

We report a case of multiple myeloma (MM) displaying an unusual course, with metastatic spread in uncommon sites (gastroduodenal and upper respiratory tract, breast, skin and liver) and with a fatal outcome. In our patient this plasma cell neoplasm was associated with a rare condition named crystal-storing histiocytosis (CSH), resulting from the storage in reactive histiocytes of crystalline immunoglobulin inclusions. These crystal-forming paraprotein components are secreted by the neoplastic plasma cells and give rise to the crystalline material of the histiocytes only after their ingestion and degradation by the same histiocytes. In this disorder crystal-storing cells may be present in various tissues (in our case mainly in bone marrow), often with functional alterations of the involved organs. In our opinion the association of this "atypical" MM with CSH is to be considered an uncommon event.