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[Comparative study on characteristics of congestive heart failure patients with preserved versus abnormal left ventricular systolic function and evaluation effects of therapy].

OBJECTIVE: To compare clinical characteristics and effects of therapy for hospitalized patients with congestive heart failure (CHF) and different left ventricular ejection fraction (LVEF) during hospitalization. METHODS: The medical records of 1 074 unselected consecutive patients with CHF who were admitted to Queen Mary Hospital from January, 2001 to January, 2002 were retrospectively reviewed. Three hundred and ninety-nine patients were categorized as having either normal left ventricular systolic function or systolic dysfunction based on the results of echocardiography. Clinical features with a slightly modified version of the Framingham criteria, laboratory results and drug therapies at discharge were compared. RESULTS: Among patients, the majority were women, 95.5% were > or =65 years and 50.6% > or =80 years of age. Classification of the severity of heart failure showed that 70.2% were New York Heart Association (NYHA) III and IV. Only 399 patients had borderline LVEF at the time of hospitalization, of these patients 191 (47.9%) had preserved systolic function (LVEF > or =0.50), and 208 (52.1%) with LVEF<0.50. Patients with LVEF > or =0.50, who tended to be elderly and more often female, exhibited a lower incidence of coronary artery disease and diabetes than patients with LVEF<0.50 (all P<0.05). Patients with preserved systolic function had a significantly higher prevalence of auricular fibrillation (P<0.05), accounting for up to 84 patients (44.0%) with it, and number of hospitalization for CHF increased. Among patients with systolic dysfunction, 22.6% were discharged on a therapeutic regimen of digoxin, 63.0% on an angiotensin-converting enzyme inhibitor (ACEI), and 12.0% on a beta-blocker, 13.9% on a calcium channel blocker. These accounted for 62.3%, 35.1%, 9.4% and 18.3% in patients with preserved systolic function, respectively. There was a higher incidence of use of digoxin (P<0.05). CONCLUSION: In hospitalized patients with heart failure, the clinical signs and symptoms of chronic heart failure are similar to those of patients with CHF, LVEF is a powerful prognostic predictor to distinguish CHF patients with normal systolic function from those with systolic dysfunction. Criteria for use of ACEI and beta-blocker are still not clear cut. It is important to differentiate CHF patients with LVEF<0.50 from that with LVEF> or =0.50 in order to achieve a better therapeutic result in the treatment of CHF.

Aged↗

Experimental model of chronic global left ventricular dysfunction secondary to left coronary microembolization.

A model of chronic left ventricular dysfunction characterized by left ventricular dilation, elevated filling pressures and histologic changes has been lacking. In this study the use of coronary microsphere embolization-induced ischemia was explored as a method of producing chronic left ventricular dysfunction. Acute ischemic left ventricular dysfunction was induced in 13 mongrel dogs with 50 microns plastic microspheres until the peak positive first derivative of left ventricular pressure (dP/dt) decreased by 25% and the left ventricular end-diastolic pressure increased to greater than or equal to 12 mm Hg. After 8 weeks of observation, hemodynamic and echocardiographic variables were measured in each dog. Acute left ventricular dysfunction resulted in a dilated left ventricle with systolic dysfunction (area ejection fraction 24 +/- 6% vs. 57 +/- 9% initially, p less than 0.01) and elevated left ventricular filling pressures. Isovolumetric relaxation was prolonged and the peak rapid filling/atrial filling velocity and integral ratios were reduced. Eight weeks after embolization, there was an increased left ventricular size (end-diastolic area 15.1 +/- 2.1 cm2 at 8 weeks vs. 13.5 +/- 1.4 cm2 early after microsphere injection, p less than 0.05), unchanged end-systolic area, improved area ejection fraction and increased left ventricular mass. Left ventricular end-diastolic pressure increased and, despite continued abnormal relaxation, the peak rapid filling/atrial filling velocity and integral ratios increased to above baseline values, demonstrating a "restrictive" pattern. Gross and histologic examination revealed diffuse, patchy scarring associated with perivascular fibrosis. Thus, coronary microsphere embolization resulted in a model of chronic moderate left ventricular systolic dysfunction and abnormal diastolic function characterized by a "restrictive" filling pattern.

Animals↗

The diagnostic accuracy and utility of a B-type natriuretic peptide test in a community population of patients with suspected heart failure.

BACKGROUND: National guidelines suggest the use of natriuretic peptides in suspected heart failure but there have been no studies comparing assays in primary care. AIM: To test and compare the diagnostic accuracy and utility of B-type natriuretic peptide (BNP) and N-terminal B-type natriuretic peptide (NT proBNP) in diagnosing heart failure due to left ventricular systolic dysfunction in patients with suspected heart failure referred by GPs to one-stop diagnostic clinics. DESIGN OF STUDY: Community cohort, prospective, diagnostic accuracy study. SETTING: One-stop diagnostic clinics in Darlington Memorial and Bishop Auckland General Hospitals and general practices in South Durham. SUBJECTS: Two hundred and ninety-seven consecutive patients with symptoms and signs suggestive of heart failure referred from general practice. METHOD: The study measured sensitivity, specificity, positive and negative predictive values (PPV, NPV), and area under receiver operating characteristic curve for BNP (near patient assay) and NT proBNP (laboratory assay) in diagnosis of heart failure due to left ventricular systolic dysfunction. The NPV of both assays was determined as a potential method of reducing the number of referrals for echocardiography. RESULTS: One hundred and fourteen of the 297 patients had left ventricular systolic dysfunction (38%). At the manufacturer's recommended cut-off of 100 pg/ml BNP gave a NPV of 82%. BNP performed better at a cut-off of 40 pg/ml with a NPV of 88%. At a cut-off of 150 pg/ml, NT proBNP gave a NPV of 92%. Using cut-offs of 40 pg/ml and 150 pg/ml for BNP and NT pro-BNP, respectively, could have prevented 24% and 25% of referrals to the clinic, respectively. CONCLUSIONS: In this setting, NT pro-BNP performed marginally better than BNP, and would be easier to use practically in primary care. A satisfactory cut-off has been identified, which needs validating in general practice. NT pro-BNP could be used to select referrals to a heart failure clinic or for echocardiography. This process needs testing in real-life general practice.

Adult↗

Quality of life in patients with signs and symptoms of heart failure--does systolic function matter?

BACKGROUND: The impaired quality of life in patients with systolic heart failure is well described. Less is known about patients with preserved systolic function (PSF) heart failure. METHODS AND RESULTS: We aimed to compare the quality of life in patients with PSF heart failure with that of those with left ventricular systolic dysfunction (LVSD) using generic and disease-specific quality-of-life questionnaires. Four hundred patients with signs and symptoms of heart failure referred for an echocardiogram to assess left ventricular function were invited to complete quality-of-life questionnaires. A total of 278 of 400 (69.5%) responses were adequate for analysis. The mean age of respondents was 72.5 (10) years; 132 (47%) were male. A total of 189 of 278 (68%) had PSF, and 89 of 278 (32%) had left ventricular systolic dysfunction (LVSD). Both groups were well matched for age, but there were more women in the PSF group (58% vs. 40%). No significant differences were found in the quality of life between PSF and LVSD patients. Women had significantly worse quality of life compared with men in both groups. CONCLUSION: Patients with PSF are an important subgroup of heart failure patients whose quality of life is as impaired as those with systolic dysfunction. These data suggest these patients warrant more care, perhaps in specialist clinics.

Aged↗

The Myocardial Performance Index detects chronic cardiac allograft dysfunction sooner than other methods.

AIM: Many noninvasive techniques have been proposed for the early detection of chronic heart graft dysfunction. Diastolic dysfunction may precede systolic dysfunction, and often is prominent; therefore, the aim of the study was to investigate the clinical and prognostic value of a Doppler-derived index of both systolic and diastolic function in heart transplanted patients (Myocardial Performance Index, MPI). METHODS: The MPI was measured in 63 consecutive patients (mean age 55 years, 49 men and 14 women) in sinus rhythm with an orthotopic heart transplantation for at least 1 year (mean 5.3 years) and in 63 age and sex-matched controls. A complete clinical examination was performed at the time of enrollment and was repeated after 3 months. RESULTS: At 3 months, 11 patients (17.5%) presented events (heart failure, hospitalisation or cardiac death). Patients were divided into 2 groups: Group A (52 patients) without events in the follow-up and Group B (11 patients) with events. The values of MPI in Group B (0.55+/-0.19) were significantly higher than values in Group A (0.34+/-0.18, P=0.001). Whereas the values of the index did not differ significantly between Group A and control group (0.34+/-0.18 vs 0.33+/-0.10, P=NS). In the univariate analysis, the population of heart transplanted patients was dichotomised in subgroups by a cut-off MPI of 0.47 and a cut-off ejection fraction (EF) of 50%. Nine patients (41%) with MPI=or>0.47 presented events, while only 2 patients (5%) with MPI<0.47 had any event (P<0.001; c2 12.9). Six patients (85%) with EF<50% had events, while only 5 patients (9%) with EF=or>50% had an event (P<0.001; c2 14). In the multivariate analysis only MPI (chi squared=22.6, P=0.018) and EF (chi squared=20.8, P=0.025) were significant independent predictors of heart failure or cardiac death. By looking at Kaplan-Meyer curves, MPI seems to be better than EF in the earlier detection of graft dysfunction. CONCLUSION: MPI, as a combined systolic and diastolic index, may detect graft dysfunction earlier than EF.

Chronic Disease↗

The influence of sex on right ventricular dysfunction in patients with severely depressed left ventricular ejection fraction.

AIM: To assess the influence of sex on right ventricular dysfunction (RVD) in patients with severe left ventricular systolic dysfunction. METHODS AND RESULTS: We studied 385 consecutive patients with left ventricular ejection fraction (LVEF) <0.35. All patients underwent invasive measurement of right ventricular and pulmonary artery pressures and evaluation of RVD by standard transthoracic echocardiography. Female patients (n=84, 21.8%) were significantly older than male patients (62.0+/-11.4 vs. 58.2+/-10.7 years), p=0.005. The prevalence of RVD was lower in women (26.5%) than in men (38.9%), p=0.03; both in patients with and without coronary artery disease (19.4% vs. 34.5% and 31.9% vs. 44.4%, respectively). Haemodynamic parameters and LVEF were similar in men and women. Low LVEF, pulmonary systolic pressure, degree of mitral regurgitation, male sex, and absence of significant coronary artery disease were independently correlated with RVD. CONCLUSION: Women with severe left ventricular systolic dysfunction have less RVD than men, despite similar haemodynamic parameters and LVEF.

Adolescent↗

Quality of life in older patients with congestive heart failure. Effects of ACE inhibitors.

Prolonged angiotensin converting enzyme (ACE) inhibition has been consistently demonstrated to increase life expectancy in symptomatic patients with congestive heart failure (CHF), and decrease morbidity in asymptomatic patients with left ventricular (LV) systolic dysfunction. However, prolonged ACE inhibition has not been shown to consistently improve the quality of life of patients with symptomatic CHF. The failure of ACE inhibition to improve quality of life cannot be readily explained, but several factors may contribute to this apparent lack of effect. First, endpoints such as death or hospitalisation are clearly easier to quantify and monitor than a patient's perception of how much CHF affects his/her life. Secondly, while ACE inhibition delays the progression of LV systolic dysfunction, which is the primary determinant of prognosis, it may not reverse the alterations in skeletal muscle vasculature, metabolism and mass, which are primarily responsible for exercise intolerance in patients with CHF. Lastly, patients with CHF, and particularly older patients, are also often incapacitated by other disease processes such as arthritis, loss of balance, pulmonary disorders and anaemia, which, to a large extent, affect the quality of their life more than LV systolic dysfunction and/or CHF.

Aged↗

The long-term outcome of patients with hypertensive cardiomyopathy.

The prognosis of dilated cardiomyopathy due to hypertension (HT-DCM) is surprisingly unknown, particularly in the absence of coronary disease and diabetes. We aimed at investigating the long-term outcome and the predictors of mortality in patients with left ventricular systolic dysfunction exclusively due to hypertension. From October 1995 to May 2001, 90 consecutive patients with echocardiographic fractional shortening (FS) < 30% and 29 control patients with FS > or = 30% were included. Obstructive coronary disease was excluded by dipyridamole myocardial perfusion imaging in all patients and coronary angiography in 60. After a mean follow-up of 4.3+/-1.6 years, the total mortality rate of HT-DCM was twice as much higher than that of patients without left ventricular systolic dysfunction (P = 0.01). In HT-DCM, the 5-year mortality rate was 26%. Univariate analyses selected age and creatinine for being positively related to mortality, and body mass index, FS and blood pressure during follow-up for being negatively related to mortality. Neither the improvement of left ventricular FS nor the decrease in left ventricular mass index was related to survival. Multivariate analysis identified (hazard ratio; 95% confidence interval) age (1.08; 1.02-1.13), body mass index (0.86; 0.75-0.98), and baseline FS (0.88; 0.78-0.98) as independent predictors of mortality. In conclusion, poor survival in HT-DCM can be anticipated by the severity of left ventricular systolic dysfunction and advanced age. Instead of ominous signs, high blood pressure and body mass may predict a more favourable prognosis.

Blood Pressure↗

Analysis of left ventricular systolic function using midwall mechanics in patients >60 years of age with hypertensive heart disease and heart failure.

Normal ejection fraction (EFs) is often equated with normal systolic function. However, midwall mechanics reveal systolic dysfunction in hypertensive heart disease accompanied by hypertrophic remodeling. Midwall mechanics are unstudied in patients with acute diastolic heart failure (HF). This study analyzed left ventricular (LV) midwall stress-shortening relations in 61 patients aged >60 years with hypertensive heart disease, HF, and normal EF. Sixty-one hypertensive patients (mean age 78 +/- 10 years) who presented with HF, each with an EF >50%, underwent echocardiography. Midwall mechanics were compared with those of 79 controls (mean age 75 +/- 8 years) without structural heart disease. Relative wall thickness (0.63 +/- 0.11 vs 0.46 +/- 0.10 mm) and LV mass (237 +/- 67 vs 177 +/- 57 g) were significantly greater in patients with HF compared with controls. Mean EFs were similar in patients with HF and controls (64 +/- 9% vs 67 +/- 9%). Although mean endocardial fractional shortening (35 +/- 7% vs 37 +/- 7%) was not significantly different, midwall shortening in patients with HF was significantly less compared with controls (16 +/- 2% vs 19 +/- 3%, p <0.05). Eighteen of the 61 patients with HF (30%) had midwall shortening that was <95% confidence intervals of the normal midwall stress-shortening relations. By this criterion, these patients had systolic dysfunction despite normal EF; they had smaller LV chambers (in dimension and volume), greater relative wall thickness, and smaller stroke volumes. In conclusion, almost 1/3 of patients hospitalized with diastolic HF had systolic dysfunction, characterized by abnormal midwall stress-shortening relations.

Aged↗

[Diabetic cardiomyopathy].

In the last decades, due to the growing number of new cases of diabetes and its cardiovascular complications, much attention has been paid to diabetic cardiomyopathy. The studies on the etiology of this condition have confirmed the role of advanced glycation end products, lipoprotein a Lp(a), apolipoprotein B (apo B) and the changes in the intracellular calcium levels. An insight in the natural history of left ventricular diastolic and systolic dysfunction in diabetes has been made possible thanks to the widespread availability of echocardiography. Diastolic dysfunction, characteristic of diabetes, precedes the onset of systolic dysfunction, which reveals at a later stage, first as exercise-induced abnormalities. The influence of diabetes on morphology of the heart manifests as hypertrophy of the left ventricle, especially in non-insulin-dependent diabetes and enlargement of the left atrial chamber. The results of the studies are not decisive as to the possible correlation between the severity of the diastolic dysfunction and the duration of diabetes or the quality of metabolic control. The presence of significant coexisting conditions, including hypertension and the complications of diabetes such as autonomic neuropathy is associated with more pronounced symptoms of diastolic dysfunction and higher values of corrected QT interval and dispersion which are considered to be the most important predictors of mortality in diabetic patients.

Cardiomyopathy, Hypertrophic↗

Acute and reversible cardiomyopathy provoked by stress in women from the United States.

BACKGROUND: A clinical entity characterized by acute but rapidly reversible left ventricular (LV) systolic dysfunction and triggered by psychological stress is emerging, with reports largely confined to Japan. METHODS AND RESULTS: Over a 32-month period, 22 consecutive patients with this novel cardiomyopathy were prospectively identified within a community-based practice in the Minneapolis-St. Paul, Minn, area. All patients were women aged 32 to 89 years old (mean 65+/-13 years); 21 (96%) were > or =50 years of age. The syndrome is characterized by (1) acute substernal chest pain with ST-segment elevation and/or T-wave inversion; (2) absence of significant coronary arterial narrowing by angiography; (3) systolic dysfunction (ejection fraction 29+/-9%), with abnormal wall motion of the mid and distal LV, ie, "apical ballooning"; and (4) profound psychological stress (eg, death of relatives, domestic abuse, arguments, catastrophic medical diagnoses, devastating financial or gambling losses) immediately preceding and triggering the cardiac events. A significant proportion of patients (37%) had hemodynamic compromise and required vasopressor agents and intra-aortic balloon counterpulsation. Each patient survived with normalized ejection fraction (63+/-6%; P<0.001) and rapid restoration to previous functional cardiovascular status within 6+/-3 days. In 95%, MRI identified diffusely distributed segmental wall-motion abnormalities that encompassed LV myocardium in multiple coronary arterial vascular territories. CONCLUSIONS: A reversible cardiomyopathy triggered by psychologically stressful events occurs in older women and may mimic evolving acute myocardial infarction or coronary syndrome. This condition is characterized by a distinctive form of systolic dysfunction that predominantly affects the distal LV chamber and a favorable outcome with appropriate medical therapy.

Acute Disease↗

Impact of renal transplantation on uremic cardiomyopathy.

In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular (LV) hypertrophy, or LV dilatation. To determine the impact of renal transplantation on uremic cardiomyopathy, all dialysis patients participating in a long-term cohort study who received a successful renal transplant were followed with echocardiography. The transplanted group comprised 102 of 433 (24%) endstage renal disease (ESRD) patients. They were significantly younger and, on starting ESRD therapy, had significantly less ischemic heart disease and cardiac failure than the overall ESRD cohort. During followup, ischemic heart disease developed in only 1 patient and none experienced cardiac failure. In the 12% (n = 12) of patients with systolic dysfunction before renal transplant, fractional shortening normalized in all patients, increasing from 21.5 +/- 4.6% to 33.5 +/- 5.6% after transplantation. In the 41% (n = 41) with concentric LV hypertrophy before transplantation, the LV mass index improved from 158 +/- 39 g/m2 to 132 +/- 39 g/m2. LV dilatation was present in 32% (n = 32) of patients before transplantation. After transplantation, LV volume fell from 116 +/- 3.1 ml/m2 to 89 +/- 21 ml/m2, and LV mass index in this group fell from 166 +/- 55 g/m2 to 135 +/- 37 g/m2. It was not possible to associate risk factors characteristic of the uremic state with the improvement in cardiac structure and function, although the fall in LV mass was significantly associated with fall in blood pressure. We conclude that correction of the uremic state by renal transplantation leads to normalization of LV contractility in systolic dysfunction, regression of hypertrophy in concentric LV hypertrophy, and improvement of cavity volume in LV dilatation. The degree of improvement suggests that dialysis patients with uremic cardiomyopathy would benefit from renal transplantation.

Adult↗

Heart failure between 1986 and 1994: temporal trends in drug-prescribing practices, hospital readmissions, and survival at an academic medical center.

Since 1987, publications in widely circulated medical journals have reported improved survival and lower hospital readmission rates when patients with heart failure and systolic dysfunction are treated with angiotensin-converting enzyme (ACE) inhibitors. We describe changes in ACE inhibitor use among patients hospitalized with heart failure between 1986 and 1993. Simultaneous trends in readmissions and survival rates are reported. Subjects were 612 consecutive patients hospitalized with a principal diagnosis of heart failure at an academic medical center during the period of Sept. 1, 1986, to Dec. 31, 1987 (interval I) or during the period Aug. 1, 1992, to Nov. 30, 1993 (interval II). Medical records were reviewed for 434 patients, consisting of all patients hospitalized with heart failure during interval II and a randomly selected 50% subset of patients hospitalized during interval I. Among 145 patients with systolic dysfunction whose medical records were reviewed, ACE inhibitor prescriptions significantly increased between interval I and interval II (43% vs 71%, p < 0.01, odds ratio 3.22, 95% confidence interval 1.62 to 6.42). Prescriptions of ACE inhibitors combined with digoxin and a diuretic also increased (37% vs 56%, p = 0.02, odds ratio 2.22, 95% confidence interval 1.14 to 4.32). Among all 612 patients, 6-month heart failure readmission rates increased from 13% to 21% (p = 0.02, odds ratio 1.79, 95% confidence interval 1.10 to 2.82). There was no significant change in survival rate between interval I and interval II, however, survival rate was marginally significantly improved among patients with systolic dysfunction. Our results suggest that drug-prescribing practices have significantly changed between 1986 and 1993. The absence of observed improvement in outcomes may result from changes in hospital admission criteria for heart failure.

Aged↗

Eplerenone : a pharmacoeconomic review of its use in patients with post-myocardial infarction heart failure.

Eplerenone (Inspra) is a selective aldosterone blocker. When added to standard medical therapy, eplerenone significantly improved morbidity and mortality in patients with left ventricular (LV) systolic dysfunction and clinical evidence of heart failure following acute myocardial infarction (MI), in a well designed, placebo-controlled trial known as EPHESUS (Eplerenone Post-acute myocardial infarction Heart failure Efficacy and SUrvival Study). Although eplerenone was generally well tolerated, it was associated with a higher incidence of hyperkalaemia than placebo.Cost-effectiveness analyses based on this trial have been performed in the US, The Netherlands, Germany, France and Spain. Direct medical costs were analysed based on prospectively collected resource-use data with local costs applied; modelling was conducted to calculate incremental costs per life-year or QALY gained, with survival curves assumed to remain parallel after treatment ended. Eplerenone was associated with a gain of 0.0304 life-years (approximately 11 days) compared with placebo during the study period. Based on these analyses, eplerenone was cost effective compared with placebo in patients with LV systolic dysfunction and heart failure after an MI when added to standard therapy for 16 months. The incremental cost per life-year gained for eplerenone versus placebo (for a range of three different life-expectancy projections) was 10,402-21,876 US dollars in the US (year 2001 costs, except for eplerenone [2004]) [equivalent to 12,274-25,814 euro; mid-2001 exchange rate], 5,365-12,795 euro for The Netherlands (year 2003 costs), 6,956-14,628 euro for Germany, 5,432-11,423 euro for France and 8,626-18,141 euro for Spain (year of costing not reported). The US, Dutch, French and Spanish analyses estimated that >90% of observations for incremental cost per life-year gained were below a threshold of 50,000 US dollars or 50,000 euro. Incremental costs per QALY gained for eplerenone versus placebo in the US, Dutch, French and Spanish analyses were 15,330-32,405 US dollars (18,089-38,238 euro), 12,148, 8,005-16,922 euro and 12,713-26, 873 euro, respectively. Clinical and pharmacoeconomic data comparing eplerenone with another active drug, such as spironolactone, in this patient population are not available. In conclusion, when added to standard therapy in patients with LV systolic dysfunction and heart failure after an acute MI, eplerenone was associated with significant reductions in mortality and morbidity compared with placebo. Despite some inherent limitations, available pharmacoeconomic data from Europe and the US indicate that eplerenone is a cost-effective treatment compared with placebo in terms of incremental cost per life-year gained in this patient population.

Aged↗

Diastolic dysfunction in aortic stenosis.

Diastolic dysfunction is characterized by an increased resistance to filling with increased diastolic filling pressures. A variety of disorders are associated with diastolic dysfunction, such as hypertrophy, structural alterations of the myocardium with increased fibrosis, myocardial scarring, or infiltrative processes. In addition to these changes, physiological abnormalities of the left ventricle with impaired relaxation, decreased diastolic filling, and increased stiffness of the myocardium can be observed. In patients with aortic stenosis, the most common cause for diastolic dysfunction is left ventricular hypertrophy. Diastolic dysfunction is found in approximately 50% of the patients with normal systolic ejection performance and in 100% of the patients with depressed function. Diastolic function appears either to be more sensitive for detection of abnormal left ventricular function in patients with aortic stenosis or to precede systolic dysfunction or both. Treatment of diastolic dysfunction is usually achieved by aortic valve replacement with regression of left ventricular hypertrophy, but in patients with decompensated aortic stenosis, a reduction of circulating blood volume to reduce diastolic filling pressures, and thus dyspnea, is often indicated. Prognosis of patients with diastolic dysfunction is usually better than that of patients with systolic dysfunction but is clearly worse than that of normal patients.

Aortic Valve Stenosis↗

Trandolapril: a newer angiotensin-converting enzyme inhibitor.

BACKGROUND: Trandolapril is a newer angiotensin-converting enzyme (ACE) inhibitor that is approved by the US Food and Drug Administration for the treatment of hypertension and for use in stable patients who have evidence of left ventricular (LV) systolic dysfunction or symptoms of chronic heart failure within the first 2 days after an acute myocardial infarction (AMI). The fixed-dose combination of trandolapril and verapamil extended release (ER) is approved for the treatment of hypertension only. OBJECTIVE: The purpose of this article was to review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of trandolapril as monotherapy and in fixed-dose combination with verapamil ER. METHODS: Relevant studies were identified through a MEDLINE/PubMed search of the English-language literature published between January 1983 and August 2002 and a review of the bibliographies of identified articles. RESULTS: Trandolapril has a sufficient duration of inhibition of plasma ACE activity to allow once-daily dosing. It is converted by esterases to the active trandolaprilat metabolite, with mean terminal disposition half-lives of < 1 and approximately 75 hours for the prodrug and metabolite, respectively. In comparative trials in the management of hypertension, trandolapril 1 to 4 mg/d was statistically indistinguishable from or superior to captopril 100 mg/d, enalapril 10 or 20 mg/d, hydrochlorothiazide (HCTZ) 25 mg/d, nifedipine ER 30 or 40 mg/d, nitrendipine 20 mg/d, perindopril 4 mg/d, and verapamil ER 120 to 240 mg/d. In the Trandolapril Cardiac Evaluation, trandolapril also significantly reduced all-cause mortality, cardiovascular mortality, sudden death, and progression to severe chronic heart failure in patients with evidence of LV systolic dysfunction after AMI. In comparative trials in the management of hypertension, the combination of trandolapril 1 or 2 mg/d and verapamil ER 180 mg/d was statistically indistinguishable from or superior to the combinations of atenolol 50 or 100 mg/d plus chlorthalidone 12.5 or 25 mg/d, captopril 50 mg/d plus HCTZ 25 mg/d, lisinopril 20 mg/d plus HCTZ 12.5 mg/d, and metoprolol 100 mg/d plus HCTZ 12.5 mg/d. The most common adverse effects of trandolapril monotherapy in clinical trials of < or = 1 year's duration included cough, dizziness, and diarrhea (frequency < or = 1.9%). The most common adverse effects of trandolapril/verapamil ER therapy in clinical trials of < or = 1 year's duration included first-degree atrioventricular block, bradycardia, constipation, cough, diarrhea, dizziness, fatigue, and dyspnea (frequency < or = 4.6%). Based on the literature search, there are no published pharmacoeconomic evaluations of trandolapril alone or combined with verapamil ER in the US health care setting. CONCLUSIONS: Based on the literature, trandolapril is a well-tolerated and effective antihypertensive agent, whether used alone or in combination with verapamil ER. These products may be valuable in patients with LV systolic dysfunction after AMI, although the combination product is approved for the management of hypertension only.

Acute Disease↗

[Electrocardiographic and angiographic follow-up of patients with hypertrophic cardiomyopathy].

Electrocardiographic follow-up was conducted for 17 patients with hypertrophic cardiomyopathy including six cases who received left ventriculographic follow-up. 1. Serial ECG changes were as follows: 1) In seven patients negativity of the T wave appeared or increased concomitantly with increased voltage of SV1 + RV5 (A-1 group). 2) In four patients, negativity of the T wave decreased or disappeared with the decreased voltage of SV1 + RV5 (A-2 group). 3) In six patients, there were insignificant changes of both T wave and SV1 + RV5 (B group). 2. Results of serial left ventriculography and biventriculography were as follows: 1) Two patients (A-1 group) showed an increased voltage of SV1 + RV5 (25 mm----48 mm, 42 mm----54 mm), and increased thickness of the apical wall (10 mm----12 mm, 8 mm----11 mm) and the anterior wall (13 mm----16 mm, 10 mm----16 mm). However, the thickness of the posterior and interventricular septal walls did not change. The configuration of the end-diastolic left ventriculogram (RAO 30 degrees) changed from a round configuration to the so-called "beak" configuration. 2) Two patients (A-2 group) showed a decreased voltage of SV1 + RV5 (81 mm----26 mm, 73 mm----53 mm), decreased thickness of the apical wall (18 mm----10 mm, 21 mm----15 mm) and the anterior wall (12 mm----9 mm, 17 mm----12 mm). The end-diastolic left ventriculogram changed from a spade-like configuration to a round configuration. In the analysis of diastolic function measured by digitized cineangiograms using a picture-analyzer, diastolic dysfunction was already present at the initial observation. The diastolic and systolic dysfunction progressed during serial observations. These patients showed the clinical pictures of dilated cardiomyopathy at the final observation. 3) Two patients with no remarkable changes of the T wave (B group) showed insignificant changes in configuration of the left ventriculogram and wall thickness. In conclusion, serial changes in configuration of the left ventricle and wall thickness, especially of the anterior and apical walls, are compatible with the serial changes of the ECG in hypertrophic cardiomyopathy. The patients whose negative T waves decreased or disappeared had diastolic dysfunction at the initial observation, and deterioration of both diastolic and systolic dysfunctions during serial observations.

Adult↗

[Incessant atrial tachycardia and peripartum cardiomyopathy--a therapeutic challenge].

Peripartum cardiomyopathy is an uncommon cause of heart failure but with serious prognosis. We report the case of a patient with peripartum cardiomyopathy presenting acute heart failure (severe biventricular systolic failure) and incessant atrial tachycardia, a rare arrhythmia difficult to control, that was responsible for cardiogenic shock, fetus death and multiple organ failure: renal failure (hemodialysis during 17 days), respiratory and hepatic failure and ischemic acute cholecystitis (treated surgically). After emergency cesarean section, heart rate control was obtained only after administering verapamil. Progressive clinical improvement with total recovery of hepatic and renal functions followed under treatment with vigorous multiple organ support. Six months after referral, the patients is doing well with normal daily life controlled with conventional therapy for heart failure, in stable sinus rhythm. Echocardiography shows a dilated left ventricle with partial resolution of systolic dysfunction rhythm. Echocardiography shows a dilated left ventricle with partial resolution of systolic dysfunction. The use of verapamil in severe biventricular systolic failure is discussed.

Cardiomyopathies↗