Role of cardiovascular magnetic resonance in suspected cardiac amyloidosis: late gadolinium enhancement pattern as mortality predictor.

BACKGROUND: Cardiac magnetic resonance (CMR) has gained a central role in the diagnosis of cardiac amyloidosis (CA). While the diagnostic role of a typical late gadolinium enhancement (LGE) pattern (global subendocardial enhancement coupled with accelerated contrast washout) has been identified, evidence is still conflicting regarding the prognostic role of such examination. METHODS AND RESULTS: We retrospectively analysed all patients referring for CMR at Niguarda Hospital (Milan, Italy) from January 2006 to January 2015 for suspected CA. Primary outcome was all-cause mortality. We identified 42 patients and divided them into 2 groups, according to the presence (Group A) or absence (Group B) of a typical amyloidosis LGE pattern. At the end of the follow-up (median 37 months, interquartile range 10-50 months), 31 patients (74%) had died. The hazard ratio for all-cause death was 3.2 (95% confidence interval [CI] 1.5-6.4, p < 0.01) for Group A versus Group B. Median survival time was 17 months (95% CI 7-42 months) for Group A and 70 months (95% CI 49-94 months) for Group B (p < 0.01). Multivariate analysis did not find any adjunctive predictive role for biventricular volumes and ejection fraction, indexed left ventricular mass, transmitral E/e' at echocardiography, age at diagnosis or serum creatinine. CONCLUSION: In our population, a typical LGE pattern was significantly associated with higher mortality. Moreover, patients with a typical LGE pattern showed a globally worse prognosis. Our data suggest that the LGE pattern may play a central role in prognostic stratification of patients with suspected CA, thus prompting further diagnostic and therapeutic measures.

A 5-year follow-up in deferasirox treatment: improvement of cardiac and hepatic iron overload and amelioration in cardiac function in thalassemia major patients.

Deferasirox (DFX) is an oral iron chelator with established efficacy and safety. We evaluated by T2* cardiovascular magnetic resonance (CMR) the efficacy of DFX in preventing and removing cardiac and liver iron load and cardiac volume changes, along 5 years in adult thalassemia major (TM) patients. Twenty-three TM patients (9 males/14 women, mean age 36 ± 4 years) were included in this study. Repeated CMR was performed to assess myocardial and liver iron load (baseline t0, after 2.5 years t1, after 5 years t2). Myocardial T2* values changed progressively and increased significantly between t0 and t2 (t0: 27.15 ± 9.58 vs t2: 36.64 ± 6.68, p = 0.0001). At baseline evaluation, a cardiac T2* value <20 ms was detected in six patients (26 %): they showed an improvement of cardiac T2* values between t0 and t1, with normal T2* levels reached in all patients at t2. In the overall population, a significant reduction of both end-diastolic and end-systolic left ventricular volumes (EDV, ESV) were detected between t0 and t2 (EDV, t0: 132 ± 31 ml vs t2: 124 ± 22 ml, p = 0.033; ESV, t0: 48 ± 14 ml vs t2: 41 ± 10 ml, p = 0.0007). A significant reduction in liver iron concentration (LIC) was detected at t1 (5.36 ± 3.58 mg/g dw at baseline vs 3.35 ± 2.68 mg/g dw at t1, p = 0.004). In patients with cardiac iron overload at baseline (n.6), mean cardiac T2* values doubled at t2, and mean LIC value is reduced of 29 %. After 5 years of treatment, DFX continually and significantly reduced myocardial and liver iron overload, and it prevented further iron deposition.

Combination of deferasirox and deferoxamine in clinical practice: an alternative scheme of chelation in thalassemia major patients.

The availability of three iron chelators improved the scenario of chelation therapy for transfusion-dependent thalassemia (TDT) patients, allowing tailoring of drugs according to the goals expected for each patient. The use of Deferiprone/Deferoxamine (DFP/DFO) combined in different schemes has been reported since many years. Only recently data from combination of Deferasirox/Deferoxamine (DFX/DFO) have been reported showing that it can be safe and efficacious to remove iron overload, particularly in patients who do not respond adequately to a single chelating agent. We investigated the efficacy, tolerability and safety of combined DFX/DFO in thalassemia major patients. Ten TDT patients have started DFX/DFO for different reasons: 1) lack of efficacy in removing liver/cardiac iron with monotherapy; 2) agranulocytosis on DFP; and 3) adverse events with elevated doses of monotherapies. The study design included: cardiac and hepatic T2* magnetic resonance (CMR), transient elastography evaluation (Fibroscan), biochemical evaluation, and audiometric and ocular examinations. The drugs' starting doses were: DFO 32 ± 4 mg/kg/day for 3-4 days a week and DFX 20 ± 2 mg/kg/day. Seven patients completed the one-year follow-up period. At baseline the mean pre-transfusional Hb level was 9.4 ± 0.4 g/dl, the mean iron intake was 0.40 ± 0.10mg/kg/day, the median ferritin level was 2254 ng/ml (range 644-17,681 ng/ml). Data available at 1 year showed no alteration of renal/hepatic function and no adverse events. A marked reduction in LIC (6.54 vs 11.44 mg/g dw at baseline) and in median ferritin (1346 vs 2254 ng/ml at baseline) was achieved. A concomitant reduction of non-transferrin-bound iron (NTBI) at six months was observed (2.1 ± 1.0 vs 1.7 ± 1.2 µM). An improvement in cardiac T2* values was detected (26.34 ± 15.85 vs 19.85 ± 12.06 at baseline). At 1 year an increased dose of DFX was administered (27 ± 6 mg/kg/day vs 20 ± 2 mg/kg/day at baseline, p=0.01) with a stable dose of DFO (32 ± 4 mg/kg/day). Combined or alternated DFX/DFO can be considered when monotherapy is not able to remove the iron overload or in the presence of adverse events.

Preoperative assessment of cardiac risk in noncardiac major vascular surgery.

We evaluated whether a preoperative clinical algorithm allows an adequate stratification in cardiac risk and the predictive value of dipyridamole thallium-201 scintigraphy and rest echocardiography for postoperative adverse cardiac outcomes. Three hundred twenty patients undergoing 338 vascular surgery procedures were prospectively stratified into low, intermediate, and high risk. The low- and intermediate-risk patients underwent surgery without further diagnostic evaluation. In 7 high-risk patients the vascular procedure was canceled (1 died of myocardial infarction at 6-month follow-up), 9 underwent presurgical myocardial revascularization (1 died of myocardial infarction), and 49 underwent vascular surgery with perioperative intensive care treatment. Hospital mortality was 3.8%. Cardiac mortality and morbidity were 1.5% and 10.4%, respectively. We observed a significant difference in "hard" (death, myocardial infarction, pulmonary edema, major arrhythmias) and "soft" (myocardial ischemia, minor arrhythmias) events between groups, p <0.001. Previous pulmonary edema was a predictive variable of cardiac outcomes (multiple logistic regression analysis). Ninety-nine of 220 intermediate-risk patients randomly underwent dipyridamole thallium-201 scintigraphy: 37 had redistribution, 10 persistent, and 52 no defects; 7 of 13 soft and hard cardiac events occurred in patients without redistribution defects. Sensitivity, specificity, and positive and negative predictive values of redistribution defects for postoperative adverse outcomes were 38%, 63%, 14%, 87%, respectively. This algorithm may provide a safe and cost-effective approach (average cost saving per patient $1,500) to cardiac risk stratification. These results suggest that routine use of dipyridamole thallium-201 scintigraphy for screening of intermediate-risk patients may not be warranted.

Thrombolysis and myocardial infarction.

Many studies suggested that the administration of streptokinase (SK) via a coronary catheter or with intravenous treatment is effective in lysing the offending thrombus which is the cause of most acute myocardial infarctions (AMI). The research carried out by the Italian Group for the Study of Streptokinase in Infarct (GISSI) which enrolled a central randomised population of 11,712 patients with AMI, clearly suggests: intravenous infusion of 1.5 million units of SK reduces in-hospital mortality from 13% to 10.7% (P = 0.0002); the decrease in mortality is 47% in patients treated within 1 hour after the onset of pain. The incidence of adverse reaction was low (4.7%). The results of the follow-up (12 months) demonstrate that beneficial effects of SK treatment on mortality were unchanged. Analysis of plasma creatine kinase curves (CK) from 7,632 patients demonstrates that the rate of input and disappearance of CK into the blood was significantly increased in SK patients. In elderly patients (greater than 65 years) the in-hospital mortality was higher (22.4% vs. 7.4%): SK is effective in patients with first AMI (19.1% vs. 22.9%). The incidence of reinfarction in the hospital phase and at the six months follow-up is higher in SK group (7.4% vs. 4.4%). Some questions remain open about the therapeutical approach to the post-thrombolytic phase and about the treatment of residual stenosis.

[Bereavement. The management of mourning: the cardiovascular physiopathology of communication]. / Bereavement. La gestione del lutto: fisiopatologia cardiovascolare della comunicazione.

Within the communication competence requested to an experienced physician, bereavement has a relevant role. A case of a patient with postinfarction cardiogenic shock admitted to a cardiosurgery department for rescue myocardial revascularization is described; the patient's wife, after communication of the death of her husband during the surgical procedure, developed an acute anterior myocardial infarction with angiographic normal coronary arteries. Pathophysiological issues concerning acute ischemic event triggers are discussed, with particular attention to emotional stress subtypes, their neuronal loops and their interactions with different cardiovascular diseases (arrhythmic, congenital, atherosclerotic). The essential variables of an adequate bereavement are discussed: set, mood, language, cultural background. The sympatho-vagal unbalance induced by emotional stress as an acute ischemic event trigger is emphasized as well as the need for more awareness by health care operators of the emotional impact and adequate management of bereavement.

[The chain of survival]. / La catena della sopravvivenza.

Coronary artery disease remains the leading cause of death in Italy as in most developed countries. Many of the victims die from sudden cardiac arrests, most commonly resulting from out-of-hospital ventricular fibrillation. The epidemiological evidence of the high incidence of sudden deaths in the small subgroup of high-risk patients and of the low incidence of events in the large subgroup of low- and intermediate-risk patients which are contributing to most of the deaths has suggested the development of emergency services and to the chain of survival concept. With the development of the automatic external defibrillator, early recognition and treatment of ventricular fibrillation by non-skilled rescuers has significantly improved the outcome of sudden death. Training is essential to provide the numerous skills required for those regularly exposed to resuscitation and also to provide the diffusion of cardiopulmonary resuscitation competence in the general population. This paper reviews the past, present and future development of the epidemiological, organizational, training, and research issues related to the chain of survival.

[Heart arrest]. / L'arresto cardiaco.

Cardiac arrest is one of the leading causes of mortality in industrialized countries and is mainly due to ischemic heart disease. According to ISTAT estimates, approximately 45,000 sudden deaths occur annually in Italy whereas according to the World Health Organization, its incidence is 1 per 1000 persons. The most common cause of cardiac arrest is ventricular fibrillation due to an acute ischemic episode. During acute ischemia the onset of a ventricular tachyarrhythmia is sudden, unpredictable and often irreversible and lethal. Each minute that passes, the probability that the patient survives decreases by 10%. For this reason, the first 10 min are considered to be priceless for an efficacious first aid. The possibility of survival depends on the presence of witnesses, on the heart rhythm and on the resolution of the arrhythmia. In the majority of cases, the latter is possible by means of electrical defibrillation followed by the reestablishment of systolic function. An increase in equipment alone does not suffice for efficacious handling of cardiac arrest occurring outside the hospital premises. Above all, an adequate intervention strategy is required. Ambulance personnel must be well trained and capable of intervening rapidly, possibly within the first 5 min. The key to success lies in the diffusion and proper use of defibrillators. The availability of new generation instruments, the external automatic defibrillators, encourages their widespread use. On the territory, these emergencies are the responsibility of the 118 organization based, according to the characteristics specific to each country, on the regulated coordination between the operative command, the crews and the first-aid means. Strategies for the handling of these emergencies within hospitals have been proposed by the Conference of Bethesda and tend to guarantee an efficacious resuscitation with a maximum latency of 2 min between cardiac arrest and the first electric shock. The diffusion of external automatic defibrillators is a preventive measure. Such equipment has permitted early defibrillation by non-medical first-aid personnel. These instruments contain software capable of recognizing an arrhythmia which may be defibrillated and of instructing the operator whether and when to press the defibrillation button. The latest instruments deliver the shock by means of a biphasic wave necessitating a lesser amount of energy which can be provided by lighter condensers. Thus such equipment weighs just a couple of kilograms. As suggested by ILCOR, for reasons of priority, such instruments should not only be available within hospitals and in ambulances but also on the territory, in particular in more crowded places. The availability of external automatic defibrillators in such places should reduce the time latency before intervention and thus increase survival. The ILCOR guidelines have suggested the constitution of an itinerary team well equipped for defibrillation and composed of trained personnel of State Institutions such as the Municipal Police, Traffic Police and the Fire Brigades. With regard to the majority of arrhythmias amenable to defibrillation which occur at home or in less crowded places, other strategies, such as primary prevention and training programs for categories at increased risk, must be employed. Antiarrhythmic drugs have long been considered the best solution for the prevention and treatment of ventricular tachyarrhythmias. However, the approach to these pathologies has drastically changed during the last few years owing to accumulating evidence in favor of defibrillators which may be implanted for the primary and secondary prevention of malignant ventricular arrhythmias. For patients with previous cardiac arrest, randomized studies have proven the advantages of such an approach compared to medical therapy. On the basis of the above, the guidelines for the use of antiarrhythmic implants have been modified. In most western countries, the laws regarding this aspect of medicine have recently been renewed. In the United States, where there is the "Law of the Good Samaritan", in order to protect and acquit persons who give first-aid, many states have adopted new laws which promote the use of external automatic defibrillators. Following recent dispositions by the President of the United States that defibrillators should be present in all Federal properties and on civil aircraft, a new Federal Law is about to pass. Italy lacks legislation regarding the use of defibrillators: in order to rectify this position, which is still anchored to existing dispositions of the civil and penal codes including those regarding the omission of first-aid, a bill entitled "The definition and modalities of the use of the external cardiac defibrillator" has recently been presented.

[Prognostic setting and bloodless hemodynamic evaluation of acute myocardial infarct with equilibrium radioisotopic ventriculography]. / Inquadramento prognostico e valutazione emodinamica incruenta nell'infarto miocardio acuto con ventricolografia radioisotopica all'equilibrio.

Forty-four consecutive patients with acute myocardial infarction were studied with equilibrium radionuclide angiography (RNA) within 24 hours from the onset of symptoms, three days after admission and three days before hospital discharge (14 +/- 3 days). To assess the prognostic value of RNA derived parameters we assessed: the ejection fraction (EF), the left ventricular end-systolic volume index (ESVI), the left ventricular end-diastolic volume index (EDVI), the cardiac index (CI), the stroke volume index (SVI) and the peak systolic pressure/end-systolic volume index ratio (PSP/ESVI); we also determined Peel's prognostic index (PI) on admission and measured systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and cardiac frequency (CF) as the same time as the radioisotopic parameters were taken. Thirty-nine patients were discharged without signs of ventricular failure with and without medical treatment (group A), 5 died during hospitalization (group B). Using EF alone, we obtained a very clear distinction between the two groups (Group A 43 +/- 12%; Group B 22 +/- 3%; p less than 0.005). Stepwise, multivariate analysis showed that, by linking PSP/ESVI to EF, we can even obtain a function that correlate better with hospital survival (F = 0.09832 X EF - 0.32035 X PSP/ESVI - 3.12981; p less than 0.002). There was good exponential correlation between EF and PSP/ESVI (r = 0.781) and this would seem to confirm that PSP/ESVI is a more sensitive contractility index for patients with a not very depressed EF.

Relationship of unrecognised myocardial infarction, diabetes mellitus and type of surgery to postoperative cardiac outcomes in vascular surgery.

OBJECTIVES: to evaluate preoperative clinical, surgical and instrumental variables as predictors of postoperative cardiac events in patients undergoing different types of elective major vascular surgery. MATERIAL AND METHODS: on the basis of an algorithm including clinical and test echocardiographic data, we prospectively stratified 604 consecutive patients into low, intermediate and high-risk groups. The value of the variables in predicting postoperative cardiac events was assessed by means of multivariate analysis. RESULTS: there were 16 major postoperative cardiac events and six of 16 postoperative deaths were cardiac related (1%). Significant predictors of cardiac complications were unrecognised myocardial infarction (odds ratio - (OR) 5.6), coronary artery disease (OR 2.5), severe hypertension (OR 2.1) and peripheral vascular surgery (OR 1.9). In the intermediate-risk group, the best correlates with cardiac complications were unrecognised myocardial infarction (OR 3.3) and diabetes (OR 2.5). CONCLUSIONS: our results suggest the importance of identifying patients with unrecognised ischaemic heart disease and of using aggressive perioperative protocols for managing diabetic patients undergoing peripheral vascular procedures.

Myocardial blood flow distribution in patients with ischemic heart disease or dilated cardiomyopathy undergoing heart transplantation.

BACKGROUND: The present investigation was designed to obtain an absolute measurement of myocardial blood flow and of its transmural distribution in ischemic heart disease and idiopathic dilated cardiomyopathy and to provide a reference standard for cardiac imaging in nuclear cardiology. METHODS AND RESULTS: Regional myocardial blood flow and its transmural distribution were estimated by the reference microsphere method in eight patients with idiopathic dilated cardiomyopathy (n = 4) or ischemic heart disease (n = 4) during heart transplant procedure. Before aortic clamping, 99mTc-labeled human albumin microspheres were injected into the left atrium while arterial blood was sampled from the aorta at a constant rate. No complications were observed during or after the procedure. From the excised heart, myocardial slices for gamma camera imaging and well counting analysis were obtained. Myocardial blood flow was assessed by a well counter, correlated with the extent of fibrosis expressed as collagen per total tissue proteins obtained from 4-hydroxyproline and glycine as determined by high-performance liquid chromatography. Microsphere distribution, as seen by gamma camera images in a different slice, was correlated with the extent of fibrosis assessed by histological analysis of the same myocardial specimen. Mean transmural myocardial blood flow was 0.49 +/- 0.17 and 0.38 +/- 0.15 mL.min-1 x g-1 in idiopathic dilated cardiomyopathy and ischemic heart disease, respectively (P < .01). Endocardial-to-epicardial flow ratio was lower in ischemic heart disease than in idiopathic dilated cardiomyopathy patients (0.99 +/- 0.33 versus 1.16 +/- 0.30, P < .05). Mean myocardial fibrosis was 9 +/- 6% in idiopathic dilated cardiomyopathy and 25 +/- 28% in ischemic heart disease. In both groups, no correlation was found between myocardial blood flow values and the extent of fibrosis. In ischemic heart disease, regional myocardial blood flow was not significantly affected by the severity of coronary stenosis (< or = 70% or > 70%) either in the endocardium (0.44 +/- 0.24 versus 0.36 +/- 0.16 mL.min-1 x g-1, P = NS) or in the epicardium (0.50 +/- 0.33 versus 0.38 +/- 0.33 mL.min-1 x g-1, P = NS). By gamma camera imaging, transmural microsphere distribution appeared more homogeneous in idiopathic dilated cardiomyopathy than in ischemic heart disease (mean coefficient variation, 18% and 27%, respectively; P < .02); the severity of perfusion impairment did not correlate with the extent of fibrosis evaluated by histological criteria. CONCLUSIONS: Heart transplant surgery offers a valuable model to assess absolute myocardial perfusion in human heart failure. Myocardial blood flow is markedly depressed in failing hearts of both ischemic heart disease and idiopathic dilated cardiomyopathy patients; a different transmural myocardial blood flow distribution is observed in ischemic heart disease than in idiopathic dilated cardiomyopathy, with prevalent endocardial perfusion in the latter but not the former condition. In patients with end-stage heart failure, myocardial blood flow appears to be similarly impaired in fibrotic and viable regions. Mechanisms other than myocardial fibrosis and coronary lesions appear to operate in determining myocardial blood flow impairment in heart failure.

Residual coronary reserve despite decreased resting blood flow in patients with critical coronary lesions. A study by technetium-99m human albumin microsphere myocardial scintigraphy.

BACKGROUND: Experimental data demonstrate the persistence of a transmural vasodilator reserve in the face of depressed resting myocardial perfusion. The present study was designed to determine whether resting myocardial hypoperfusion indicates exhausted coronary reserve (CR). METHODS AND RESULTS: Fifteen patients with stable angina, isolated left anterior descending coronary artery (LAD) stenosis, and no previous myocardial infarction were evaluated by means of 99mTc human albumin microsphere scintigraphy. Regional myocardial perfusion and CR were assessed at baseline and after LAD papaverine (10-12 mg) by means of two microsphere injections in the left ventricle and compared with five normal subjects. Two 300-second scans were obtained with a mobile gamma camera positioned in the 70 degrees left anterior oblique projection; actual microsphere distribution after papaverine was obtained by image subtraction. The two arterial input functions (basal and papaverine) were measured from the first-pass time-activity curves and validated with the reference arterial sample technique. From the comparison of circumferential profile analysis between patients and normal subjects, nine patients (group 1A) showed perfusion defects at rest (reduction of percent radioactivity below 2 SD of normal subjects) in the LAD territory, and the other six (group 1B) showed homogeneous perfusion. CR (papaverine/resting perfusion) was 3.8 +/- 0.2 and 1.51 +/- 0.27 in normal subjects and in ischemic patients, respectively (p < 0.01). Despite resting hypoperfusion, group 1A showed a papaverine-recruitable CR similar to that of group 1B (1.57 +/- 0.33 and 1.43 +/- 0.16, respectively, p = NS). CONCLUSIONS: In patients with stable angina pectoris, isolated LAD stenosis, and no previous myocardial infarction, microsphere scintigraphy disclosed a high incidence of resting perfusion defects; in those patients, a residual CR was observed despite decreased resting blood flow.

[Comparison of 6 and 8 French catheters for arterial catheterization and coronarography: prospects of the development of coronarography in ambulatory care]. / Confronto fra cateteri 6 ed 8 French per cateterismo arterioso e coronarografia: prospettive di sviluppo della coronarografia in regime ambulatoriale.

The aim of this study was to evaluate day-hospital coronary angiography as a valid method to reduce hospital recovery costs and patient waiting lists. We evaluated its technical feasibility by randomizing sixty hospital patients. These were divided into two groups, and 6 or 8 French Judkins of Amplatz coronary angiography catheters were used for each group following the Judkins technique. Patients were invited to walk after four hours. Local complications, the number of catheters used, their stability and maneuverability, as well as the radiological resolution of the image were evaluated. No major cardiac complications occurred. One transient cerebral ischemic episode during 6F coronary angiography was quickly resolved by medical therapy. Two local haemorrhages and three cases of hypotension were observed in the 8 French group, while minor bleeding phenomena were similar in both groups (3 vs 5). Differences occurred in local haematoma incidence after 24 hours (13 in 8F vs 2 in 6F); there was no difference in the number of catheters used, the completion time of the examination, or the radiological resolution. Maneuverability and stability of the 6F group were reduced, but not so much as to compromise examination. The AA concluded that 6F catheters are useful in day-hospital coronary angiography, with a similar examination quality, and a reduction in local complication.