Rita Mariotti

Acute Effects of Triiodothyronine (T3) Replacement Therapy in Patients with Chronic Heart Failure and Low-T3 Syndrome: A Randomized, Placebo-Controlled Study

CONTEXT Low-T(3) syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T(3) replacement therapy in patients with low-T(3) syndrome and ischemic or nonischemic dilated cardiomyopathy (DC). DESIGN A total of 20 clinically stable patients with ischemic (n = 12) or nonischemic (n = 8) DC were enrolled. There were 10 patients (average age 72 yr, range 66-77; median, 25-75th percentile) who underwent 3-d synthetic L-T(3) infusion (study group); the other 10 patients (average age 68 yr, range 64-71) underwent placebo infusion (control group). Clinical examination, electrocardiography, cardiac magnetic resonance, and bio-humoral profile (free thyroid hormones, TSH, plasma renin activity, aldosterone, noradrenaline, N-terminal-pro-B-Type natriuretic peptide, and IL-6) were assessed at baseline and after 3-d synthetic L-T(3) (initial dose: 20 microg/m(2) body surface.d) or placebo infusion. RESULTS After T(3) administration, free T(3) concentrations increased until reaching a plateau at 24-48 h (3.43, 3.20-3.84 vs. 1.74, 1.62-1.93 pg/ml; P = 0.03) without side effects. Heart rate decreased significantly after T(3) infusion (63, 60-66 vs. 69, 60-76 beats per minute; P = 0.008). Plasma noradrenaline (347; 270-740 vs. 717, 413-808 pg/ml; P = 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P = 0.02), and aldosterone (175, 152-229 vs. 231, 154-324 pg/ml; P = 0.047) significantly decreased after T(3) administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T(3) administration, left-ventricular end-diastolic volume (142, 132-161 vs. 133, 114-158 ml/m(2) body surface; P = 0.02) and stroke volume (40, 34-44 vs. 35, 28-39 ml/m(2) body surface; P = 0.01) increased, whereas external and intracardiac workload did not change. CONCLUSIONS In DC patients, short-term synthetic L-T(3) replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T(3) administration.

Early Results of Transmyocardial Revascularization With a Holmium Laser

BACKGROUND Transmyocardial laser revascularization (TMLR), a surgical technique designed to improve perfusion in the ischemic myocardium by creating transmural channels, has been performed thus far using a carbon dioxide laser, with apparently gratifying early results. We have investigated clinically TMLR using a holmium laser as sole therapy for patients with coronary artery disease that is not amenable to traditional treatment such as coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. METHODS From November 1995 to December 1996, 16 patients underwent TMLR using a holmium laser. Their mean age was 68 +/- 6 years and 75% were men. Previous coronary artery bypass grafting or percutaneous transluminal coronary angioplasty had been performed in 81% and 31% of the patients, respectively. Before operation, their mean anginal class was 3.4 +/- 0.5 and their mean left ventricular ejection fraction was 0.49 +/- 0.06. Six patients had unstable angina. RESULTS There were no operative deaths. The mean duration of TMLR was 27 +/- 13 minutes and the mean duration of the entire operation was 120 +/- 40 minutes. There were no major postoperative complications and the mean hospital stay was 8 +/- 4 days. There were 2 late deaths, 1 that occurred 40 days after TMLR as a result of stroke and 1 that occurred 4 months after TMLR as a result of myocardial infarction. Current survivors have been followed up for a mean of 10 +/- 4 months (range, 3 to 15 months), with 7 patients followed up for 1 year. At last follow-up, the mean anginal class had decreased to 1.8 +/- 0.7 (p = 0.001) and the patients had increased exercise tolerance and a reduced number of hospitalizations. However, no statistically significant changes in the percentage of segments with fixed or reversible ischemia and no statistically significant differences in the viability scores of lased and nonlased segments were observed. CONCLUSIONS Transmyocardial laser revascularization using a holmium laser is a simple technique with low operative risk and low morbidity. Early results confirm that clinical improvement is obtained in most patients, although significant changes in myocardial perfusion are not evident in the short term.

Pancreas transplant alone determines early improvement of cardiovascular risk factors and cardiac function in type 1 diabetic patients

Background. The effects of pancreas transplant alone (PTA) on cardiovascular risk factors (CRF) and cardiac function in type 1 diabetes mellitus (T1DM) patients are still unsettled. Methods. We studied 13 T1DM patients who received PTA with portal drainage and 11 matched control patients. Parameters of glucose and lipid metabolism and several additional classic CRF were assessed before and up to 6 months posttransplant. Cardiac morphology and function were assessed by Doppler echocardiographic examination. Results. Insulin independence was promptly achieved and then maintained after PTA. Total and low-density lipoprotein cholesterol levels were significantly lower after transplantation, whereas high-density lipoprotein cholesterol and triglyceride concentrations did not change. Both systolic and diastolic blood pressure values and fibrinogen levels improved significantly. In addition, PTA determined a significant amelioration of several morphologic and functional cardiac indices. None of the measured parameters changed in the control patients. Conclusions. PTA with portal drainage induces an early improvement of CRF and ameliorates cardiac function in patients with T1DM.

Usefulness of Carotid Intima-Media Thickness Measurement and Peripheral B-Mode Ultrasound Scan in the Clinical Screening of Patients with Coronary Artery Disease

Previous observational studies have shown a relationship between carotid intima-media thickness (IMT) and coronary artery disease (CAD). In this study the authors evaluated the accuracy of the common carotid IMT measurement in predicting the presence and severity of CAD and the additional information offered by the detection of carotid, iliac, and lower limb plaques. One hundred and fifty consecutive patients were subjected to coronary angiography and carotid, iliac, and lower limb ultrasound scan. The mean value of six IMT measurements of the far wall of the common carotid artery was calculated in each patient. The mean IMT was significantly correlated to the number of stenosed coronary vessels (r = 0.43, p < 0.001), although the positive and negative predictive value of mean IMT in identifying patients with CAD was low (81% and 46%, respectively). The combined information offered by IMT measurements and peripheral (carotid, iliac, and lower limb) plaque detection was then used to obtain the best multivariate regression model able to predict CAD status. The multivariate model showed a highly significant multiple correlation coefficient (r = 0.60, p < 0.0001) and a sharp improvement in the negative predictive value (92%) with respect to the univariable model. B-mode ultra sound scan including common carotid IMT measurement and peripheral plaque detection may be of clinical value in the screening of patients with CAD.

Myocardial delayed enhancement in paucisymptomatic nonischemic dilated cardiomyopathy.

OBJECTIVES We investigated the prognostic role of myocardial fibrosis by delayed enhancement (DE) cardiovascular magnetic resonance (CMR) in nonischemic dilated cardiomyopathy (NICM) patients with no or mild symptoms of heart failure (HF). METHODS A prospective cohort of 125 NICM patients (82 males, age 59±14years, mean±SD) with echocardiographic evidence of left ventricular (LV) systolic dysfunction (mean ejection-fraction 33±10%), without (stage B) or with history of mild HF symptoms (stage C, NYHA classes I-II) was enrolled. The end-point was a composite of cardiac death and HF hospitalization. RESULTS Fifty (40%) patients showed myocardial DE, representing 12±7% of LV mass. During a median follow-up of 14.2months, 16 (32%) patients with DE experienced a composite event versus only 6 (8%) patients without DE (Kaplan-Meier survival curve, p=0.001). After correction for age, CMR-derived LV and right ventricular volumes, echocardiographic measurements of LV diastolic function and Doppler-estimated systolic pulmonary artery pressure, the presence of DE remained a strong and independent predictor of cardiac death or HF hospitalization (hazard ratio: 5.32, 95% confidence intervals 1.60 to 17.63, p=0.006). CONCLUSIONS In NICM patients with no or mild HF symptoms, the presence of myocardial DE is a strong predictor of worse clinical outcome even after correction for other established prognostic determinants. Contrast-enhanced CMR may be useful in prognostic stratification from the early stages of NICM.

The impact of coronary artery disease on the coronary vasomotor response to nonionic contrast media.

BACKGROUND Coronary artery disease (CAD) alters the vasomotor response to a variety of pharmacological agents. We tested the hypothesis that CAD also has an impact on the coronary vasomotor response to radiologic contrast media. METHODS AND RESULTS We performed quantitative coronary angiography in 42 patients without angiographic evidence of CAD and 38 patients with CAD in the left coronary artery. Angiographically smooth coronary segments (n=235) were analyzed for changes on luminal diameters and coronary venous oxygen saturation in response to 3 media: the nonionic dimer iodixanol, the nonionic monomer iopromide, and the ionic agent ioxaglate. In subjects without CAD, we assessed the effects of intracoronary administration of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine and of the cyclooxygenase inhibitor indomethacin on such changes. Iodixanol induced coronary vasodilation in subjects without CAD (8.8+/-8.6%, P<0.001). Patients with CAD exhibited no significant diameter changes in segments >/=20 mm apart from a stenosis (4.7+/-9.4%, P=NS) and significant constriction in segments <20 mm from a stenosis (-3.8+/-4.6%, P<0. 05). Similar results were obtained with iopromide, but no changes were found with ioxaglate. All contrast media induced transient (<35 seconds) increases in coronary venous oxygen saturation in all subjects. Indomethacin, but not N(G)-monomethyl-L-arginine, blunted the vasodilating effect of iodixanol and iopromide (by 80% and 76%, respectively; P<0.001). CONCLUSIONS Nonionic contrast media induce a vasodilatory response in normal vessels not by a mechanism involving increased flow or endothelial nitric oxide synthesis, but rather by depending on preserved vascular cyclooxygenase activity. CAD changes normal epicardial vasodilatory response into vasoconstriction.

Total Thyroidectomy in Patients with Amiodarone-Induced Thyrotoxicosis and Severe Left Ventricular Systolic Dysfunction

CONTEXT Patients with amiodarone-induced thyrotoxicosis (AIT) and left ventricular (LV) systolic dysfunction have a high mortality rate. Usually, medical therapy is the first choice for AIT patients, whereas the role of the thyroidectomy is unsettled. OBJECTIVE The objective of the study was to evaluate the effect of a total thyroidectomy on cardiac function and survival of AIT patients with severe LV systolic dysfunction. DESIGN This was a retrospective cohort study. SETTINGS The study was conducted at a tertiary university center. PATIENTS All AIT patients (n=24; nine patients with type 1 AIT, 15 patients with type 2 AIT) referred to the Department of Endocrinology and submitted to a total thyroidectomy at the Department of Surgery, both at the University of Pisa, during the years 1997-2010. INTERVENTION The intervention was a total thyroidectomy. MAIN OUTCOME MEASURE LV ejection fraction (EF) after the thyroidectomy and survival in December 2011 were measured. RESULTS All enrolled patients had previously undergone to medical treatment for AIT, as appropriate, without achieving euthyroidism. Patients with moderate to severe LV systolic dysfunction (EF<40%, group 1, n=9) or with mild systolic dysfunction (40%≤EF≤50%, group 2, n=5) were compared with patients with normal systolic function (EF>50%, group 3, n=10). Two months after thyroidectomy, under levothyroxine replacement therapy, LVEF improved in patients with LV systolic dysfunction, particularly in those of group 1, in whom it increased from 28.2±7.2 to 38.3±6% (P=0.007). On the contrary, LVEF did not significantly change in group 3 (from 57.1±3.0 to 59.8±6.6%, P=0.242). The mean follow-up was 67±42 months. No death occurred during and 2 months after surgery. One death occurred in one patient of group 1, 30 months after the thyroidectomy, due to acute myocardial infarction. No patient had relevant complications of thyroidectomy. CONCLUSIONS Total thyroidectomy, by rapidly restoring euthyroidism, may improve cardiac function and reduce the risk of mortality in AIT patients with severe LV dysfunction.

Symptomatic improvement after transmyocardial laser revascularization: how long does it last?

BACKGROUND The aim of this study was to determine whether short-term clinical improvement after isolated transmyocardial holmium laser revascularization (TMLR) in patients with coronary artery disease not amenable to traditional treatment is maintained through a longer follow-up. METHODS Between November 1995 and June 1999 34 patients underwent TMLR (mean age, 67+/-7 years); previous revascularization procedures had been performed in 76%. Preoperatively, mean angina class was 3.6+/-0.5 in 12 patients with unstable angina; mean left ventricular ejection fraction was 47%+/-9%. RESULTS There was 1 early death due to low cardiac output. Mean duration of TMLR and of the entire operation was 25+/-12 minutes and 125+/-43 minutes, respectively. There were no major postoperative complications; mean hospital stay was 8+/-4 days. There were 8 late deaths caused by stroke (2 patients), cardiac failure (1 patient), and myocardial infarction (5 patients). Follow-up of current survivors ranges from 4 to 48 months (mean, 32+/-12 months). At 1-year follow-up mean angina class was 1.8+/-0.8; but at a later follow-up (mean, 35+/-10 months) it significantly increased to 2.2+/-0.7 (p = 0.005). Three-year actuarial survival was 76%+/-8% and freedom from cardiac events 44%+/-10%. CONCLUSIONS Our results show that after initial clinical improvement many patients experience return of angina or cardiac events; this questions the long-term symptomatic benefit of TMLR.

Weight loss and quality of life in chronic heart failure patients

Objectives To evaluate the impact of a planned body weight reduction on quality of life (QoL) in obese/overweight chronic heart failure (CHF) patients. Methods Thirty-four obese/overweight chronic heart failure patients (24 men, mean age 67.8 ± 9.4 years) underwent a 6-month dietary programme. An assessment of clinical and biochemical parameters was executed before and after dietary programme. The QoL was judged by means of the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and at the end of the programme. Results End-study BMI (P < 0.005) and body weight (P < 0.04) values were significantly reduced. We observed a significant improvement in the mean New York Heart Association (NYHA) functional class value (P < 0.02) and in the left ventricle ejection fraction (LVEF) (P < 0.05). The end-study KCCQ scores were significantly increased in seven out of eight domains. We identified a cut-off value of body weight loss of 3 kg to separate responder patients from the nonresponder ones. Only responder group patients showed a significant variation in BMI (P < 0.04), body weight (P < 0.03), mean NYHA class value (P < 0.05), LVEF (P < 0.05). Moreover, all KCCQ domain scores significantly increased in the responder group only. Conclusion A diet-based body weight reduction improved the quality of life and, perhaps, the cardiac function. Benefits are already evident with a small reduction in body weight.

Evaluation of pulmonary vascular pressures in cardiac patients : the role of the chest roentgenogram

In 77 patients (34 with left heart valvulopathy, 17 with dilated cardiomyopathy, and 26 with chronic coronary artery disease) pulmonary vascular pressures were estimated from the chest film by means of a new scoring system. Standard chest x-ray films taken immediately before diagnostic right and left cardiac catheterization were analyzed independently by three readers without knowledge of the hemodynamic findings. The radiographic signs were subdivided into three groups as follows, and to each one a score derived from a retrospective statistical analysis was attributed: (A) signs of interstitial edema, (B) patterns of pulmonary blood flow distribution, and (C) alterations in the pulmonary arteries. The sum of the scores of groups A and B x-ray findings correlated well with pulmonary wedge pressure, and the sum of the scores of groups A, B, and C correlated more strongly with the mean pulmonary artery pressure. These results confirm that it is possible, in patients with chronic heart disease, to assess accurately the pulmonary artery and wedge pressures by means of the noninvasive and easily performed chest roentgenogram.