Combined flow-based imaging assessment of optimal cardiac resynchronization therapy pacing vector: a case report.

BACKGROUND: There are still many pendent issues about the effective evaluation of cardiac resynchronization therapy impact on functional mitral regurgitation. In order to reduce the intrinsic difficulties of quantification of functional mitral regurgitation itself, an automatic quantification of real-time three-dimensional full-volume color Doppler transthoracic echocardiography was proposed as a new, rapid, and accurate method for the assessment of functional mitral regurgitation severity. Recent studies suggested that images of left ventricle flow by echo-particle imaging velocimetry could be a useful marker of synchrony. Echo-particle imaging velocimetry has shown that regional anomalies of synchrony/synergy of the left ventricle are related to the alteration, reduction, or suppression of the physiological intracavitary pressure gradients. We describe a case in which the two technologies are used in combination during acute echocardiographic optimization of left pacing vector in a 63-year-old man, Caucasian, who showed worsening heart failure symptoms a few days after an implant, and the effect of the device's optimization at 6-month follow-up. DISCUSSION: The degree of realignment of hemodynamic forces, with quantitative analysis of the orientation of blood flow momentum (φ), can represent improvement of fluid dynamics synchrony of the left ventricle, and explain, with a new deterministic parameter, the effects of cardiac resynchronization therapy on functional mitral regurgitation. Real-time three-dimensional color flow Doppler quantification is feasible and accurate for measurement of mitral inflow, left ventricular outflow stroke volumes, and functional mitral regurgitation severity. CONCLUSION: This clinical case offers an innovative and accurate approach for acute echocardiographic optimization of left pacing vector. It shows clinical utility of combined three-dimensional full-volume color Doppler transthoracic echocardiography/echo-particle imaging velocimetry assessment to increase response to cardiac resynchronization therapy, in terms of reduction of functional mitral regurgitation, improving fluid dynamics synchrony of the left ventricle.

Platypnea-orthodeoxia syndrome : Orthostatic dyspnea and possible pathophysiological substrates.

Platypnea-orthodeoxia syndrome (POS) is a rare disorder characterized by the emergence of a right-to-left shunt at the intracardiac or intrapulmonary level. The clinical picture is distinguished by shortness of breath that worsens on standing due to an accentuation of oxygen desaturation, and instead improves, at least partly, in the recumbent position. In this article we present a brief review of the pathophysiology of POS, as well as its clinical picture, diagnostic assessment, and preferential therapeutic options. Pathophysiological issues that are still not completely understood or much debated are outlined. The currently accepted pathophysiological concepts are presented and a summary of the main diagnostic and therapeutic tools is provided.

Effects of limiting fluid intake on clinical and laboratory outcomes in patients with heart failure. Results of a meta-analysis of randomized controlled trials.

BACKGROUND: The guidelines of the Scientific Societies of Cardiology recommend limiting fluid intake as a nonpharmacological measure for the management of chronic heart failure (HF). However, many patients with HF may suffer from severe thirst. A meta-analysis was performed to evaluate the effect of limiting fluid consumption based on various clinical and laboratory outcomes in patients with chronic HF. METHODS: Only randomized controlled trials comparing liberal and restricted fluid oral intake in patients with HF were included. Primary outcomes were HF hospitalizations and all-cause mortality. Secondary outcomes were the sensation of thirst, the duration of therapy with intravenous diuretics, and the serum levels of creatinine, sodium, and B-type natriuretic peptide (BNP). RESULTS: Six studies met the inclusion criteria. Significant heterogeneity was detected for the majority of outcomes. In 5 studies, patients with restricted fluid intake compared to patients with free consumption of beverages had similar rehospitalization and mortality rates. There were no differences regarding patients' sense of thirst (4 studies), duration of intravenous diuretic treatment (2 studies), serum creatinine levels (5 studies), and serum sodium levels (5 studies). Serum BNP levels were significantly higher in the group with free fluid intake (4 studies). CONCLUSION: In patients with HF, liberal fluid consumption does not seem to exert an unfavorable impact on HF rehospitalizations or all-cause mortality. Further randomized controlled trials are warranted to definitively confirm the present findings.

Cardiovascular risk associated with celecoxib or etoricoxib: a meta-analysis of randomized controlled trials which adopted comparison with placebo or naproxen.

AIM: The present meta-analysis attempted to assess whether an unfavourable cardiovascular risk profile could be identified in the case of two COX2 selective inhibitors (COXIBs), namely celecoxib and etoricoxib. Based on the data from the literature, our meta-analysis aimed to assess the probability of major cardiovascular events reported with the use of celecoxib or etoricoxib and compare this with the results seen in patients assigned to the placebo group. Furthermore, the risk of cardiovascular events found by using celecoxib or etoricoxib was also compared with that associated with the use of naproxen, a nonselective non-steroidal anti-inflammatory drug (NSAID) chosen as our reference drug. METHODS: The studies had to be randomized controlled trials with at least 4-week duration. Studies were included if they compared celecoxib or etoricoxib against placebo or naproxen. Moreover, the selected studies had to have determined the risk, odds or incidence of myocardial infarction, stroke or cardiovascular death. For the comparisons versus placebo, the endpoints of interest were "serious vascular events", "non-fatal myocardial infarction", "non-fatal stroke" and "death from cardiovascular causes", whereas "myocardial infarction" and "stroke" were the endpoints of interest concerning the comparison versus naproxen. RESULTS: From the evaluation of 41 studies comparing celecoxib with placebo, we found a significantly higher incidence of serious vascular events in the celecoxib group compared to controls treated with placebo (rate ratio 1.598, 95% CI: 1.048 to 2.438; P=0.029). Furthermore, in patients allocated to treatment with celecoxib, we found an incidence rate of non-fatal acute myocardial infarction that was three times higher compared with the placebo group (rate ratio 3.074, 95% CI: 1.375-6.873, P=0.006). In contrast, we did not find any significant difference with regard to the incidence of nonfatal stroke and that of death from cardiovascular causes by comparing celecoxib and placebo. In addition, by examining cardiovascular outcomes that emerged from the 17 trials which compared etoricoxib with placebo, it was not possible to demonstrate statistically significant differences in incidence for each of the explored endpoints. With regard to the comparison of each coxib with the non-selective COX2 inhibitor naproxen, we did not find any significant difference for either the odds of myocardial infarction or that of stroke. CONCLUSION: On the basis of our meta-analysis, we can state that symptomatic benefits induced by the prolonged administration of celecoxib may be partially invalidated by a concomitant increase in vascular risk, particularly the increased risk of myocardial infarction found in celecoxib-treated patients, compared to controls taking placebo. In contrast, treatment with etoricoxib proved not to result in an increased risk of serious vascular events when compared with both the placebo and naproxen. Our meta-analysis also denotes that the alternative to COXIBs, represented by naproxen, does not show significant benefit in terms of reduced cardiovascular risk. Therefore, considering that the increase in incidence rate of cardiovascular events associated with treatment with celecoxib is small in absolute terms, it is reasonable to state that celecoxib is still a drug whose benefits outweigh the potential adverse effects on the cardiovascular system.

In right or biventricular chronic heart failure addition of thiazides to loop diuretics to achieve a sequential blockade of the nephron is associated with increased risk of dilutional hyponatremia: results of a case-control study.

AIM: Chronic hyponatremia is frequently found in some syndromes characterized by widespread edema coupled to impairment in arterial effective circulating volume, such as congestive chronic heart failure (CHF). In this setting, it is unclear whether the hyponatremia itself makes this condition worse or whether it represents a simply marker of decompensation. The factors responsible for development of hyponatremia in CHF have not exhaustively been elucidated yet. The aim of this paper was to ascertain whether some laboratory, clinical and therapeutical factors are able to predict occurrence of hyponatremia in CHF patients. METHODS: A case-control study was carried out by recruiting 57 CHF patients, whose 19 characterized by hyponatremia (serum Na+<135 mEq/L) and 38 controls, matched for age, sex, etiology of CHF, time elapsed since beginning of both symptoms and diuretic therapy. Eligibility criteria included right or biventricular heart failure in NYHA class III, absence of hyponatremia at the first visit and therapy at enrollment with oral dose not less than 175 mg per week of furosemide or equivalent weekly dose of torsemide. Exclusion criteria were electrostimulation therapies (pace-maker or cardiac resynchronization therapy), documented episodes- one or more- of infective gastroenteritis or diarrhea and use of any drug influencing neuroendocrine mechanisms of arginin-vasopressin (AVP) secretion, such as opiates, tetracyclines, phenothiazines, lithium, serotonin selective reuptake inhibitors (SSRIs) etc. RESULTS: At univariate analysis, intensive intravenous (iv) therapy with furosemide (one or more courses), ascites, mixed regimen with thiazide diuretic plus furosemide, high (>3 ng/mL/h) plasma renin activity, serum creatinine ≥2,2 mg/dl and oligoanuria were shown to be associated with hyponatremia. At multivariate analysis a role of predictor of hyponatremia was maintained by combined therapy with thiazide diuretic plus furosemide (OR=35.68 95%CI: 2.83-449.37 P=0.0057) as well as by intensive iv furosemide therapy (OR=12.44 95%CI: 1.207-128.27 P=0.0342). CONCLUSION: Inhibition of free water clearance by thiazides may account for association found between their use and hyponatremia development in congestive CHF setting. Even though loop diuretics are known to promote free water excretion, in our experience hyponatremia might have been favored by iv furosemide high doses, because drop in effective circulating volume and further impairment in arterial underfilling due to overzealous iv loop diuretic administration are able to foster AVP non osmotic release, thereby leading to hemodilution hyponatremia.

In chronic heart failure with marked fluid retention, the i.v. high doses of loop diuretic are a predictor of aggravated renal dysfunction, especially in the set of heart failure with normal or only mildly impaired left ventricular systolic function.

AIM: In the presence of resistance to oral diuretics in chronic heart failure (CHF) patients with extreme hydrosaline retention, among the proposed therapeutic options the administration of high doses of loop diuretics - either intravenous (i.v.) boluses or i.v. continuous infusion - should first of all be considered. Nevertheless, the use of this therapy may lead to the risk of further aggravation of frequently coexisting renal dysfunction, especially when loop diuretics such as furosemide (FUR), torasemide etc. are administered at excessive doses leading to hypotension, hypoperfusion and/or relative dehydration in patients with decompensated CHF who could have benefit from intensive unloading therapy. The aim of this study was to identify the clinical and hematochemical markers which are able to predict a possible decline or rapid deterioration of renal function implying a rise in serum creatinine (Cr) >25% of its basal value, i.e. the so-called aggravated renal dysfunction (ARD), typically occurring during intensive unloading therapy with i.v. FUR or other loop diuretics, administered to CHF pts with extreme fluid retention. METHODS: The protocol of our case-control observational study established to enroll every CHF patient who was demonstrated to develop a rise in Cr suggestive of ARD at the end of i.v. diuretic therapy (VI-VIII day). For each case enrolled, 3 patients at least were selected as controls, matched for age, sex and time elapsed from the beginning of the signs and symptoms of CHF. For the prediction of the dependent variable, represented by ARD diuretic infusion-related, the following independent variables were considered: creatinine clearance (Cr clear) <60 mL/min, Cr clear expressed as a continuous variable (Cr clear continuous), daily dose of i.v. furosemide ≥ 125 mg, left ventricular ejection fraction (LVEF), CHF with normal (≥ 50%) LVEF (HFNEF), urinary sodium concentration (U Na+) ≥ 40 mEq/L, U Na+expressed as a continuous variable (U Na+ continuous), sodium fractional excretion (FE Na+) >2%, urine/plasma concentration ratios for creatinine (U/P cr) <10, for urea (U/P urea) <5 and for osmolality (U/P osmolal) <1.1, mean duration of the symptoms of CHF, history of pre-existing parenchymal renal disease . The values of U Na+, FE Na+, U/P Cr, U/P urea and U/P osmolal were measured after discontinuance of diuretic oral therapy for four days, before the onset of intensive i.v. diuretic administration, so as to identify the patients with pathological values of tubular renal function indexes, known to be not interpretable in the presence of diuretics, suggestive of possible preexisting anatomic renal damage (acute tubular necrosis prior to onset of iv diuretic therapy). RESULTS: Nineteen 19 CHF patients with ARD and 60 controls were enrolled. At univariable analysis, Cr clear <60 mL/min, Cr clear continuous, daily dose of iv furosemide ≥ 125 mg, LVEF, HFNEF, FE Na+>2%, Na+≥ 40 mEq/L and U Na+ continuous were shown to be associated with ARD. At multivariate analysis, the role of prognostic indicator of ARD was maintained by daily dose only of iv FUR ≥125 mg (OR: 7.2088 95% CI: 1.3096-39.6802 P=0.0232). By using the 2x2 contingency tables, a qualitative interaction was identified by crossing ARD ­ outcome variable - against dose of iv FUR ≥ 125 mg/day - exposure variable - and by subsequently stratifying by the HFNEF. Actually, a significant association with ARD was not present in any CHF patient with dilated left ventricle treated with high dosage of iv FUR, whereas a highly significant association with ARD was observed in HFNEF patients (OR: 72 95% CI: 6.601-785.2694 P=0.00001) who had experienced the same high iv fur dose. CONCLUSION: In CHF patients with widespread edema refractory to oral diuretic, ARD can be propitiated by high dosages of i.v. FUR, when not associated with other treatments to preserve the effective circulating volume and renal flow. The HFNEF patients appear to be more prone to ARD related to i.v. high dosages of FUR, perhaps because their hemodynamics is more seriously harmed by the drop, FUR-related, in venous return and cardiac preload, as compared to CHF patients with reduced (45-30%) LVEF.

[Renoprotective effect of small volumes of hypertonic saline solution in chronic heart failure patients with marked fluid retention: results of a case-control study]. / Renoprotektiver Effekt kleiner Volumina hypertoner Kochsalzlösung bei Patienten mit chronischer Herzinsuffizienz und Ödembildung: Ergebnisse einer Fall-Kontroll-Studie.

During intensive therapy of chronic heart failure (CHF) patients with marked fluid retention using high doses of i.v. furosemide the additional effect of agents which might exert osmotic attraction of interstitial fluids has been proposed. They are thought to impede the impairment of renal blood supply and glomerular filtration rate, which may be caused by a combined action of cardiac preload acute reduction, hypotension and neurohormonal activation.We therefore assessed in CHF patients with NYHA class III and BNP values from 900 to 1500 pg/ml, who were treated with i.v. furosemide, the predictors of iatrogenic short term creatinine impairment by means of a case-control observational study from two centers. Patients with CHF had been treated for 6-8 days with intravenous loop diuretics alone or with an additional i.v. administration of other agents (plasma expanders, albumin, mannitol, inotropic support etc.). A rise in serum creatinine ≥ 25% of the basal value was considered as renal impairment.A total of 15 cases and 38 controls were enrolled. At univariate analysis, serum creatinine basal value ≥ 2.2 mg/dl, absence of hypertonic saline solution (HSS) in the therapeutic protocol, hyposodic diet and refractory oligoanuria were associated with an increased risk of worsening renal function precipitated by i.v. diuretic therapy. At multivariate analysis as a predictor of loop diuretic-related renal function impairment, we found a serum creatinine ≥ 2.2 mg/dl at baseline (OR: 63.33, 95% CI: 3.68-1088.73, p=0.0043) and the absence of HSS in the therapeutic regimen (OR: 25.0461, 95% CI: 2.07-302.53, p=0.0113). Moreover, in multivariate analysis ascites had some predictive value of renal deterioration (OR: 13.28, 95% CI: 1.0055-175.41, p=0,0495).

The risk of worsening CHF is positively related to unitary increase in mitral regurgitation size: a case-cohort study derived from a II NYHA class CHF patient population.

AIM: The passage from II to III New York Heart Association (NYHA) class is indicative of cardiopulmonary impairment and unfavourable prognosis. Among chronic heart failure(CHF) II NYHA class patients, the topic has been debated what criteria have be assumed for identifying the patients prone to accelerated progression towards III NYHA class. METHODS: A case cohort study, including a number of CHF II NYHA class patients, was carried out, to evaluate the role as predictor of CHF worsening of some ultrasonographic parameters, listed as follows: left ventricular ejection fraction, as continuous and as a dichotomous variable, i.e. subdivided as follows: 1) LVEF larger than 40% and 2) LVEF ranged from 30% to 40%; mitral regurgitation (MR), as continuous and as a dichotomic variable (i.e. moderate-to-severe MR, defined by transmitralic jet planimetric area estimated as larger than 20% of left atrium area), restrictive LV filling pattern and pulmonary systolic arterial pressure >40 mmHg. The pts were subdivided in 3 categories, as follows:1) diastolic CHF, i.e. heart failure with normal or only mildly impaired left ventricular ejection fraction - 20 patients; 2) systolic CHF, i.e. heart failure with reduced left ventricular ejection fraction - 19 patients; and 3) CHF due to "organic" mitral insufficiency-19 patients. All patients were treated with pharmacologic therapy, according to their respective clinical features and typology of basal heart disease. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for the composite endpoint death and hospitalization due to worsening CHF were investigated, concerning each of the above-mentioned criteria. Moreover, the odds ratios (OR) were calculated, by not conditional logistic regression analysis, to achieve information about risk of death and/or worsening CHF, as well as the respective profiles of risk, assessed by relative risk (RR). RESULTS: From 173 followed-up patients, 58 patients,70+/-12 aged, whose 15 cases (transition to III NYHA class) and 43 controls, were included in retrospective analysis. Notewhorty, moderate-to-severe MR only seemed to play a role as reliable predictor of worsening CHF(sensitivity: 93.3%; specificity: 69.7%; PPV: 51.8%; NPV: 96.7%; RR:15.93; OR: 32.3), as its sensitivity and PPV, particularly, were shown to exceed far and away the values of sensitivity and PPV associated to each of other echographic and/or clinical variables. Nevertheless, at multivariate analysis,MR expressed as continuous variable only, but not as "categorical" variable-was demonstrated to independently predict the transition from II to III NYHA class, over two years clinical follow up. CONCLUSION: The present data seem to support the view that the larger regurgitant jet of mitral insufficiency, the higher the risk of worsening CHF during a two years follow up. Likewise, it is plausible the moderate-severe MR represents a predictor of increased risk of transition to III NYHA class among the CHF II NYHA class patients. In addition, this study seems to indicate that a surgical therapy (prosthetic replacement or mitral valvuloplasty)should always be planned in the case of II NYHA class CHF patient who has been recognized affected by moderate-to-severe MR, since the chances of successful pharmacological prevention of clinical impairment in this setting turned out to be very slight.

Association between myocardial right ventricular relaxation time and pulmonary arterial pressure in chronic obstructive lung disease: analysis by pulsed Doppler tissue imaging.

This study assessed right ventricular function in chronic obstructive lung disease and pulmonary hypertension by Doppler tissue imaging. Doppler echocardiography of the right ventricle and Doppler tissue imaging of the tricuspid annulus were performed in 63 subjects: 20 healthy controls, 20 with lung disease, and 23 with both lung disease and pulmonary hypertension. Two-dimensional tricuspid systolic plane excursion was lower in patients with pulmonary hypertension than in the other 2 groups. Doppler tricuspid inflow measurements distinguished patients in both of the diseased groups from the control subjects, but they did not differentiate patients with pulmonary hypertension from those without it. The ratio of peak E-wave to peak A-wave velocities derived by Doppler tissue imaging was significantly lower and the myocardial acceleration time longer in both groups of lung disease than in the control group. Only myocardial relaxation time distinguished the 3 groups (all P <.01); a gradual increase in time occurred, with the shortest time seen in controls, a longer time in patients with chronic obstructive lung disease without pulmonary hypertension, and the longest time in patients with lung disease and pulmonary hypertension. In the overall population including subjects with at least minimal tricuspid regurgitation, myocardial relaxation time was positively related to pulmonary systolic pressure. In conclusion, Doppler tissue imaging distinguishes subsets of patients affected by lung disease with or without pulmonary hypertension and identifies patients with different levels of pulmonary artery systolic pressure.

Regional diastolic function in normotensive versus hypertensive subjects: comparison using Doppler myocardial imaging.

BACKGROUND: Pulsed Doppler myocardial imaging (DMI) is a new technique that makes it possible to obtain an on-line quantitative assessment of wall motion in different myocardial segments through sample-volume placement. Therefore, this tool is suitable for identifying changes in regional diastolic function in uncomplicated arterial hypertension. In this study, we examined standard Doppler-derived indexes of global left ventricular diastolic function and regional diastolic parameters obtained by pulse-wave DMI in a population of hypertensive patients, comparing them with the indexes found in a control group of normotensive subjects. METHODS: Thirty-six patients with uncomplicated hypertension and 10 normotensive subjects (all males) underwent a complete Doppler echocardiographic examination and a pulsed DMI assessment of 4 different myocardial segments: basal and middle septum, basal and middle lateral wall. RESULTS: The 2 groups were comparable in age and heart rate, but body mass index, systolic and diastolic blood pressure and left ventricular mass index were higher in hypertensives. All of the transmitral diastolic measurements were impaired in hypertensives, without any difference in the Doppler indexes of global systolic function. While there were no changes in the regional systolic measurements, most of the DMI parameters for diastolic function changed significantly in all 4 of the segments examined, with a greater statistical difference at the basal and middle septum. We found a relationship between the number of segments involved in the diastolic dysfunction (ie with peak velocity E/A < 1) and the degree of impairment of the transmitral E/A ratio solely in the hypertensive population. CONCLUSIONS: DMI is a useful tool for distinguishing left ventricular diastolic function in hypertensive patients and it provides information about the extent and degree of diastolic impairment in different myocardial segments. The basal and middle septum present more evident diastolic alterations. Minor but significant changes can be identified at the basal and middle lateral walls. The higher the prevalence of the myocardial segments involved in diastolic dysfunction, the greater the impairment of the global diastolic function of the left ventricle will be.

[Clinical aspects of dilated cardiomyopathy in pediatric age]. / Aspetti clinici della cardiomiopatia dilatativa in età pediatrica.

Natural history and prognostic factors of dilated cardiomyopathy in pediatric age are not well identified so far. The course of the disease, often, presents "odd" characteristics: some of the patients show clinical improvement, someone remains unchanged and some of them have a negative evolution in a very short time. It is necessary to identify the group of patients having a poor outcome in order to define prognostic factors of impending death so that a cardiac transplant could be offered to them as a reasonable therapeutic choice. Twenty-two children, 9 males and 13 females (median age 5 +/- 5 years) with dilated cardiomyopathy were studied. Their natural history was followed for a period of 40 +/- 30 months. Clinical data, laboratory studies (electrocardiogram, Holter monitoring, echocardiogram M-mode, 2-D, Doppler and chest X-ray) were taken into consideration. At the end of follow-up period 7 patients showed improvement in cardiac status (31.8%), 7 remained unchanged (31.8%) and 8 (36%) got worse; 9 died. The survival curve showed a rate of 72% at 12 months and of 59.3% at 60 months. Of 9 died patients, 2 died suddenly and seven for congestive heart failure. Clinical findings and laboratory investigations of 13 survived patients (Group I) and 9 died patients (Group II) were compared to establish the risk factors of poor outcome. The fractional shortening is the only significant factor of poor outcome (p less than 0.025). Other negative factors were identified more in Group II than in Group I.(ABSTRACT TRUNCATED AT 250 WORDS)