The worrisome liaison between left ventricular systolic dysfunction and mitral annulus calcification in type 2 diabetes without coronary artery disease: data from the SHORTWAVE study.

BACKGROUND AND AIM: Mitral annulus calcification (MAC) is a marker for coronary artery disease (CAD) and predicts poor outcome in the general population. No data are available on MAC in patients with type 2 diabetes. In these patients we assessed prevalence of MAC and the relation between MAC and left ventricular (LV) systolic function. METHODS AND RESULTS: As many as 386 patients with type 2 diabetes without CAD were studied with Doppler echocardiography. LV systolic dysfunction was defined by analyzing 120 healthy subjects. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (peak S') were considered as indexes of LV circumferential and longitudinal shortening and classified low if <89% and <8.5 cm/s, respectively (10th percentiles of controls). Patients who had MAC (107 = 28%) were older with longer duration of DM and were receiving more anti-hypertension medications than those who had not. At echocardiographic evaluation patients with MAC showed higher LV mass, larger left atrial volume (LAV), reduced sc-MS (88.4 ± 14.9 vs 92.6 ± 14.3%; p = 0.01) and peak S' (8.9 ± 2.2 vs 10.0 ± 2.0 cm/s; p < 0.001) than patients without MAC. Multiple logistic regression demonstrated older age (OR 1.03 [IC 1.01-1.06], p = 0.009), larger LAV (OR 1.19 [IC 1.11-1.28], p < 0.001) and combined reduction in sc-MS and peak S' (OR 3.00 [IC 1.57-5.72], p = 0.001) as independent factors associated with MAC. CONCLUSIONS: MAC is detectable in one fourth of patients with type 2 diabetes without CAD and is mostly related to LV systolic dysfunction expressed as combined impairment of LV circumferential and longitudinal fibers, independent of age and LAV.

Moderate alcohol use and health: a consensus document.

AIMS: The aim of this consensus paper is to review the available evidence on the association between moderate alcohol use, health and disease and to provide a working document to the scientific and health professional communities. DATA SYNTHESIS: In healthy adults and in the elderly, spontaneous consumption of alcoholic beverages within 30 g ethanol/d for men and 15 g/d for women is to be considered acceptable and do not deserve intervention by the primary care physician or the health professional in charge. Patients with increased risk for specific diseases, for example, women with familiar history of breast cancer, or subjects with familiar history of early cardiovascular disease, or cardiovascular patients should discuss with their physician their drinking habits. No abstainer should be advised to drink for health reasons. Alcohol use must be discouraged in specific physiological or personal situations or in selected age classes (children and adolescents, pregnant and lactating women and recovering alcoholics). Moreover, the possible interactions between alcohol and acute or chronic drug use must be discussed with the primary care physician. CONCLUSIONS: The choice to consume alcohol should be based on individual considerations, taking into account the influence on health and diet, the risk of alcoholism and abuse, the effect on behaviour and other factors that may vary with age and lifestyle. Moderation in drinking and development of an associated lifestyle culture should be fostered.

Adjuvant trastuzumab cardiotoxicity in patients over 60 years of age with early breast cancer: a multicenter cohort analysis.

BACKGROUND: Adjuvant Trastuzumab with chemotherapy is the gold standard for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (HER2+ EBC). Older patients have been largely under-represented in clinical trials, and few data on Trastuzumab cardiotoxicity have been reported in this subgroup. PATIENTS AND METHODS: Four hundred and ninety-nine consecutive HER2+ EBC patients were treated with adjuvant trastuzumab and chemotherapy (aTrastC) at 10 Italian institutions. We evaluated disease prevalence and patient characteristics in the patients older than 60 years of age (over-60), prevalence of aTrastC cardiotoxicity and risk factors. RESULTS: There were 160 'over-60' patients (32%), in whom a higher prevalence of hypertension, diabetes, renal dysfunction, dyslipidemia and treatment with ACEi (40 versus 8%) and beta blockers (20 versus 8%) was found than in the younger patients (339 = 68%). Clinical heart failure occurred in 6% of the 'over-60' and in 2% of the younger patients. A reduction in left ventricular ejection fraction of >10 points was detected in 33% of the 'over-60' and in 23% of the younger patients (all P < 0.05). aTrastC was discontinued in 10% of the 'over-60' and in 4% of the younger patients (P = 0.003), restarted in 44% of the 'over-60' and in 58% of the younger women (P = ns). CONCLUSION: In clinical practice, 32% of HER2+ EBC patients treated with aTrastC are 'over-60'. These patients have an increased cardiovascular risk profile and develop aTrastC cardiotoxicity commonly.

Severe intravascular haemolysis as delayed manifestation of perivalvular leak in patients with mitral valve replacement: a report of two cases.

Haemolytic anaemia following mitral valve replacement is uncommon, however in patients who suffer from some degree of perivalvular leak, severe and potentially fatal recurrent intravascular haemolysis can be an annoying problem. We report the cases of two patients with severe haemolytic anaemia observed some years after mitral valve replacement. In one of the two patients the presence of an association between a valvular leak after mitral valve replacement and a calcific atrial wall produced severe and recurrent haemolysis that required multiple blood transfusions. In the second patient the presence of a single valvular leak after mitral valve replacement induced an episode of haemolytic anaemia some years after the operation. These cases point out that in case of unexplained worsening anaemia, a transthoracic (TT) and transesophageal (TE) echocardiogram should be performed, and the possibility of atrial wall alterations in the producing of anaemia should be kept in consideration. In these cases reoperation resolved the recurrence of anemization.

[Atheroembolic renal disease]. / La malattia renale ateroembolica.

Atheroembolic renal disease can be defined as renal failure due to occlusion of the renal arterioles by cholesterol crystal emboli usually dislodged from ulcerated atherosclerotic plaques of the aorta. Atheroembolic renal disease is part of multisystem disease, since the embolization usually involves other organ systems such as the gastrointestinal system, central nervous system, and lower extremities. The kidney is frequently involved because of the proximity of the renal arteries to the abdominal aorta, where erosion of atheromatous plaques is most likely to occur. Embolization may occur spontaneously or after angiographic procedures, vascular surgery, and anticoagulation. In the last decade, atheroembolic renal disease has become a recognizable cause of renal disease. An ante-mortem diagnosis of the disease is possible in a significant proportion of cases as long as the level of diagnostic suspicion is high. The disease can severely affect kidney and patient survival. Although no specific treatment has been proven efficacious, use of statins may be justifiable and such therapy would be a reasonable choice for future treatment trials.

Cardiac arrest in a patient with a mobile right atrial thrombus in transit and amyloidosis.

Primary amyloidosis is a rare disorder in which insoluble fibers are deposited in tissue and organs, impairing their function. Cardiac involvement occurs in up to 50% of patients with primary amyloidosis. We describe a case of a 75-year-old admitted to our department after he had a sudden cardiac arrest due to massive bilateral thrombotic occlusion of the pulmonary arteries. The echocardiogram revealed many atrial thrombi swirling inside the right atrium and protruding into the tricuspid valve partly occluding it. Severe concentric hypertrophy of the left ventricle was also present with a preserved ejection fraction. The right ventricle was dilated, hypertrophic and ipokinetic with a severe tricuspidal insufficiency that permitted estimation of a severe pulmonary hypertension. All these characteristics were highly suggestive for an infiltrative form of hypertrophic cardiomyopathy. The final diagnosis was amyloidosis.

Left atrial dilatation in systolic heart failure: a marker of poor prognosis, not just a buffer between the left ventricle and pulmonary circulation.

BACKGROUND: The relation between systolic pulmonary pressure (sPAP) and left atrium in patients with heart failure (HF) is unclear. Diastolic dysfunction, expressed as restrictive mitral filling pattern (RMP), and functional mitral regurgitation (FMR) are associated with both LA enlargement and increased sPAP. We aimed to evaluate whether atrial dilation might modulate the consequences of RMP and FMR on the pulmonary circulation of patients with HF with reduced ejection fraction (HFrEF). METHODS: 1256 HFrEF patients were retrospectively recruited in four Italian centers. Left ventricular (LVD) and atrial (LAD) diameters were measure by m-mode, and EF were measured. RMP was defined as E-wave deceleration time lower than 140 ms. FMR was quantitatively measured. sPAP was evaluated based on maximal tricuspid regurgitant velocity and estimated right atrial pressure. RESULTS: Final study population was formed by 1005 patients because of unavailability of sPAP in 252 patients. Mean EF was 33 ± 3, 35% had RMP, 67% had mild, and 26% moderate-to-severe FMR. 69% of patients had increased sPAP. A significant association was observed between sPAP and EF, RMP, FMR, and LAD (p < 0.0001 for all). At multivariate analysis, LAD was positively associated with sPAP (p < 0.0001) independently of EF, RMP, and FMR. Analogously, LAD (p < 0.05) was associated with more severe symptoms and worse prognosis after adjustment for LV function and FMR. CONCLUSION: LA dilation was positively associated with sPAP independently of EF, RMP, and FMR. This highlights that LA size should be considered a marker of the severity of the disease.

Brain cancer mimicking an acute coronary syndrome.

The authors report the case of a 62-year-old woman admitted to hospital for episodes of chest pain with ischemic abnormalities at ECG without enzyme release. Coronography confirmed a normal coronary tree with mild ascending aortic dilatation. Subsequent diagnostic and clinical examinations resulted normal. Episodes of chest pain and dyspnea persisted over the following days. Administration of nitrates, calcium antagonist, diuretic, antidepressant agents for suspected syndrome X led to partial improvement of clinical symptoms. The patient was discharged from the hospital. A few days later she was referred to the neurology department because of an episode of transient dysarthria, hyposthenia and paresthesis localized to the right lower and upper limbs associated with chest pain. A brain computed tomography showed an expansive solid mass. Nuclear magnetic resonance imaging and stereotaxis biopsy confirmed the etiology of the lesion to be a glioblastoma. The patient died soon thereafter from respiratory and cardiocirculatory arrest.

Use of cardiopulmonary exercise testing with hemodynamic monitoring in the prognostic assessment of ambulatory patients with chronic heart failure.

OBJECTIVES: We studied whether direct assessment of the hemodynamic response to exercise could improve the prognostic evaluation of patients with heart failure (HF) and identify those in whom the main cause of the reduced functional capacity is related to extracardiac factors. BACKGROUND: Peak exercise oxygen consumption (VO2) is one of the main prognostic variables in patients with HF, but it is influenced also by many extracardiac factors. METHODS: Bicycle cardiopulmonary exercise testing with hemodynamic monitoring was performed, in addition to clinical evaluation and radionuclide ventriculography, in 219 consecutive patients with chronic HF (left ventricular ejection fraction, 22 +/- 7%; peak VO2, 14.2 +/- 4.4 ml/kg/min). RESULTS: During a follow-up of 19 +/- 25 months, 32 patients died and 6 underwent urgent transplantation with a 71% cumulative major event-free 2-year survival. Peak exercise stroke work index (SWI) was the most powerful prognostic variable selected by Cox multivariate analysis, followed by serum sodium and left ventricular ejection fraction, for one-year survival, and peak VO2 and serum sodium for two-year survival. Two-year survival was 54% in the patients with peak exercise SWI < or = 30 g x m/m2 versus 91% in those with a SWI >30 g x m/m2 (p < 0.0001). A significant percentage of patients (41%) had a normal cardiac output response to exercise with an excellent two-year survival (87% vs. 58% in the others) despite a relatively low peak VO2 (15.1 +/- 4.7 ml/kg/min). CONCLUSIONS: Direct assessment of exercise hemodynamics in patients with HF provides additive independent prognostic information, compared to traditional noninvasive data.

Hemodynamic profile of submaximal constant workload exercise in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Constant workload exercise on an upright bicycle at submaximal levels of exercise intensity is frequently used in physical training programs. Nevertheless, only a few data are currently available on the hemodynamic changes induced by constant workload exercise in patients with heart failure. The aim of this study was to assess the hemodynamic response during submaximal constant-workload exercise at 2 different work rates in patients with heart failure. The hemodynamic profile was assessed by means of right-sided cardiac catheterization in 21 men with moderate heart failure during submaximal-constant workload exercise performed on an upright bicycle for 15 minutes. The intensity of constant work rate exercise was selected during a previous symptom-limited or maximal test. The first submaximal test was performed at the level of the anaerobic threshold workload, corresponding to 64% of peak work rate, and the other test at 70% of anaerobic threshold workload (42% of peak work rate). During both submaximal tests, a marked increase in right heart pressure was observed as compared with baseline. The increase in systolic pulmonary artery pressure was statistically not different between the 2 tests (from 40 +/- 18 to 66 +/- 20 mm Hg during exercise at the anaerobic threshold workload, and from 39 +/- 16 to 63 +/- 21 mm Hg during exercise under anaerobic threshold). The increase in pulmonary arterial wedge pressure was similar (from 20 +/- 10 to 35 +/- 13 mm Hg during exercise at the anaerobic threshold, and from 19 +/- 9 to 32 +/- 12 mm Hg during the other test). Cardiac output and heart rate were significantly higher during submaximal exercise at a higher workload, paralleling the behavior of oxygen uptake. Finally, the hemodynamic profile during submaximal exercise at the anaerobic threshold workload was quite similar to that observed during symptom-limited exercise. Thus, in patients with heart failure, submaximal exercise performed at a constant workload, even at low exercise intensity, may determine relevant pressure changes in pulmonary circulation.

Mechanisms and immediate outcome of in-hospital cardiac arrest in patients with advanced heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

To differentiate patients with congestive heart failure who are more prone to develop malignant ventricular tachyarrhythmias or severe bradyarrhythmias as the terminal event, we retrospectively evaluated a group of 48 patients with advanced heart failure who experienced a monitored cardiac arrest during hospital stay. We found no significant differences with respect to several variables, apart from clinical status, which was worse in patients whose cardiac arrest was precipitated by severe bradycardia or electromechanical dissociation.

Contribution of left atrial pressure and dimension to signal-averaged P-wave duration in patients with chronic congestive heart failure.

In a group of patients with chronic heart failure, a longer P-wave duration on signal-averaged electrocardiogram was found in those patients with higher pulmonary capillary wedge pressure, whereas the left atrium end-systolic diameter was not significantly different. Furthermore, an acute reduction in pulmonary capillary wedge pressure induced by sodium nitroprusside infusion was associated with a reduction in P-wave duration.

Dobutamine-induced changes in pulmonary artery pressure in patients with congestive heart failure and their relation to abnormalities of lung diffusing capacity.

Short-term infusion of dobutamine may determine a mild, statistically significant increase in pulmonary artery pressure from baseline in 30% of patients with moderate to severe heart failure despite systemic effects (changes in cardiac index and systemic vascular resistance) similar to those observed in patients showing a large reduction in right heart pressures. The increase in pulmonary artery pressure observed seems to be associated with a lower pulmonary diffusing capacity, probably reflecting a reduction in recruitment and distension capacity of pulmonary circulation.

Effects of maximally tolerated oral therapy on the six-minute walking test in patients with chronic congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy.

In patients with heart failure, therapy with "maximally tolerated" oral doses of diuretics, vasodilators, and digitalis results in a significant increase in the distance walked during the 6-minute walking test, compared with conventional therapy at "standard" doses, indicating an improvement in exercise tolerance. The 6-minute walk test is a simple, inexpensive, and well-tolerated test to measure changes in exercise tolerance induced by pharmacologic interventions, even on a short-term basis.

Rate of progression of valvular aortic stenosis in adults.

Until recently the hemodynamic severity of valvular aortic stenosis (AS) was evaluated only by cardiac catheterization. Now, Doppler echocardiography allows a noninvasive and accurate assessment of AS severity and can be used to study its progression with time. The progression of AS was assessed during a follow-up period of 6 to 45 months (mean 18) by serial Doppler examinations in 45 adult patients (21 men and 24 women, mean age 72 +/- 10 years) with isolated AS. The following parameters were serially measured: left ventricular outflow tract diameter and velocity by pulsed Doppler, peak velocity of aortic flow by continuous-wave Doppler, to calculate peak gradient by the modified Bernoulli equation, and aortic valvular area by the continuity equation. At the initial observation, 13 of 45 patients (29%) were symptomatic (1 angina, 1 syncope and 11 dyspnea); during follow-up, 25 (55%) developed new symptoms or worsening of the previous ones (5 angina, 3 syncope and 17 dyspnea); 11 underwent aortic valve replacement and 3 died from cardiac events. Baseline peak velocity and gradient ranged between 2.5 and 6.6 m/s, and 25 and 174 mm Hg, respectively; aortic area ranged between 0.35 and 1.6 cm2. With time, mean peak velocity and gradient increased significantly from 4 +/- 0.7 to 4.7 +/- 0.8 m/s (p less than 0.01), and 64 +/- 30 to 88 +/- 30 mm Hg (p less than 0.01), respectively. A concomitant reduction in mean aortic area occurred (0.75 +/- 0.3 to 0.6 +/- 0.15 cm2; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of isolated left ventricular diastolic dysfunction in hypertension as assessed by combined transmitral and pulmonary vein flow Doppler study.

In a relatively large population of patients with treated systemic hypertension and normal left ventricular systolic function, prevalence of abnormalities of left ventricular diastolic function, as assessed by Doppler echocardiographic study of mitral and pulmonary vein flow, was high, with 51% of patients showing indirect signs of increased left ventricular end-diastolic pressure. Furthermore, our data documented that a "normal" mitral flow profile does not exclude the presence of an abnormality of left ventricular filling, which could be otherwise identified by combined analysis of a pulmonary vein flow profile.

Pulmonary artery hypertension in adult patients with symptomatic valvular aortic stenosis.

Pulmonary hypertension (PH) has been reported in patients with valvular aortic stenosis (AS) and has been found to be associated with a more severe clinical picture and a poor prognosis after aortic valve replacement. The aim of this study was to assess the prevalence of PH in adult patients with symptomatic AS undergoing cardiac catheterization, and to evaluate the relation between pulmonary artery (PA) systolic pressure and hemodynamic and clinical variables to further clarify the pathogenetic mechanisms. We assessed right-sided heart hemodynamics during cardiac catheterization in 388 patients with symptomatic isolated or predominant AS. PA systolic pressure between 31 and 50 mm Hg was used to define mild to moderate PH, whereas PA systolic pressure >50 mm Hg was used to define severe PH. PA systolic pressure showed no significant difference according to age and sex, although it was significantly higher in patients in New York Heart Association functional classes III and IV and in patients with coexistent systemic hypertension than in the others. PH was absent in 136 patients (35%, group 1), mild to moderate in 196 patients (50%, group 2), and severe in 58 patients (15%, group 3). Only the prevalence of overt heart failure was significantly higher in group 3 patients. AS severity was similar among the 3 groups, and PA systolic pressure showed no relation to aortic valve area in the entire population. Also, a poor correlation was found between PA pressure and left ventricular (LV) ejection fraction (r = -0.28), with several patients having moderate or severe PH despite a preserved LV systolic function. PA systolic pressure significantly correlated with LV end-diastolic pressure (r = 0.50) and with PA wedge pressure (r = 0.84). Furthermore, transpulmonary pressure gradient, an index of resistance across the pulmonary vascular bed (obtained as the difference between PA mean and PA wedge pressure), was significantly higher in patients with PH, especially in those with a marked increase in PA systolic pressure, suggesting a reactive component of PH.

Left ventricular remodeling in valvular aortic stenosis. Echocardiographic and clinical changes in two patients during follow-up.

Left ventricular (LV) response to chronic pressure overload of aortic stenosis (AS) is usually characterized by an increase of wall thickness without cavity enlargement ("concentric hypertrophy"). During follow-up, two patients with AS developed relevant structural and functional changes of the left ventricle, ie, progressive LV dilatation, wall thinning, and reduction of systolic performance. At the same time, the patients had clinical symptoms of congestive heart failure. The pathophysiologic relevance of this form of LV remodeling in AS is discussed.

Ventricular arrhythmias in adult aortic stenosis: prevalence, mechanisms, and clinical relevance.

With the longer life expectancy of the population, calcific aortic stenosis has become a common cardiac problem in the elderly. When patients with moderate to severe aortic stenosis become symptomatic, the prognosis is usually poor in absence of valve replacement and sudden death is a feared complication. It has been hypothesized that malignant ventricular arrhythmias could be responsible for the high incidence of sudden death in symptomatic patients with aortic stenosis. The purpose of this review is to analyze the prevalence, the electrophysiologic mechanisms, and the possible role of ventricular arrhythmias in the development of symptoms and in the outcome of adult subjects with aortic stenosis.

Assessment of left ventricular filling in patients with systemic hypertension. A Doppler echocardiographic study.

To assess left ventricular (LV) diastolic function in patients with hypertension, a Doppler echocardiographic study of transmitral blood flow (TBF) was performed in 46 hypertensive patients (H), 18 without (H1) and 28 with (H2) left ventricular hypertrophy and in 25 age-matched normal subjects (N). All patients showed normal systolic function. The following indices of Doppler TBF were measured: peak flow velocity during early filling (Evel), atrial systole (Avel) and their ratio (E/Avel); area under early filling phase (Earea), area under atrial systole (Aarea), expressed as a percentage of total diastolic area and their ratio (E/Aarea); deceleration half-time (DHT) of early filling phase. When compared with N, H1 and H2 showed significant reductions in early filling indices and an increase in atrial contribution parameters. (Evel = 0.62 +/- 0.1(N), 0.52 +/- 0.1(H1) P less than 0.01, 0.44 +/- 0.1(H2) P less than 0.001; Earea = 56 +/- 5(N), 48 +/- 5(H1) P less than 0.001, 43 +/- 6(H2) P less than 0.001; Avel = 0.49 +/- 0.1(N), 0.59 +/- 0.1(H1) P less than 0.01, 0.69 +/- 0.14(H2) P less than 0.001; Aarea = 26 +/- 5(N), 41 +/- 4(H1) P less than 0.001, 47 +/- 7(H2) P less than 0.001). Also DHT was significantly prolonged, compared with N (80 +/- 12 msec), in H1 (90 +/- 12 msec, P less than 0.01) and H2 (105 +/- 20 msec, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)