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P de Groote

Publications and source records attributed to P de Groote.

At least 19 recordsLinked to original sources

[Hyponatraemia, antagonists of the antidiuretic hormone and cardiac failure].

Hyponatraemia is a common clinical finding in cardiac failure, complicating the management of these patients. Vasopressin plays a fundamental role in the physiopathology of the hyponatraemia of cardiac failure and binds to two distinct specific receptors, receptor V1a and V2. The V2 receptors, situated in the renal collecting duct, control the resorbtion of free water. The V1a receptors, present everywhere, are responsible for the vasoconstrictive effect of vasopressin. Specific antagonists of vasopressin receptors are being evaluated in pathologies associated with hyponatraemia. The preliminary results in patients with cardiac failure are encouraging and mortality studies are underway.

Antidiuretic Hormone Receptor Antagonists↗

Heart failure with preserved systolic function: a diagnostic algorithm for a pragmatic definition.

Heart failure is a major health problem which often concerns the elderly. Prevalence of heart failure with preserved systolic function is increasing and varies from 40 to 50%. In the literature, and in the large epidemiological studies, it is commonly designed with the term of "diastolic heart failure", even if a precise analysis of diastolic function is not performed. A diagnostic algorithm is proposed in order to better define the concept of heart failure with preserved systolic function. It consists of seven steps from symptoms and clinical signs to the echocardiographic analysis of diastolic function, in order to confirm the definition of heart failure with preserved systolic function.

Algorithms↗

Cardiac resynchronisation therapy reduces functional mitral regurgitation during dynamic exercise in patients with chronic heart failure: an acute echocardiographic study.

OBJECTIVES: To assess non-invasively the acute effects of cardiac resynchronisation therapy (CRT) on functional mitral regurgitation (MR) at rest and during dynamic exercise. METHODS: 21 patients with left ventricular (LV) systolic dysfunction and functional MR at rest, treated with CRT, were studied. Each patient performed a symptom-limited maximal exercise with continuous two dimensional Doppler echocardiography twice. The first exercise was performed with CRT; the second exercise was performed without CRT. Mitral regurgitant flow volume (RV), effective regurgitant orifice area (ERO) and LV dP/dt were measured at rest and at peak exercise. RESULTS: CRT mildly reduced resting mitral ERO (mean 8 (SEM 2) v 11 (2) mm(2) without CRT, p = 0.02) and RV (13 (3) v 18 (3) ml without CRT, p = 0.03). CRT attenuated the spontaneous increase in mitral ERO and RV during exercise (1 (1) v 9 (2) mm(2), p = 0.004 and 1 (1) v 8 (2) ml, p = 0.004, respectively). CRT also significantly increased exercise-induced changes in LV dP/dt (140 (46) v 479 (112) mm Hg/s, p < 0.001). CONCLUSION: Attenuation of functional MR, induced by an increase in LV contractility during dynamic exercise, may contribute to the beneficial clinical outcome of CRT in patients with chronic heart failure and LV asynchrony.

Aged↗

Effects of bisoprolol in patients with stable congestive heart failure.

AIM OF THE STUDY: To analyze the effect of bisoprolol in patients with stable congestive heart failure and who tolerated beta-blockers. MATERIAL AND METHODS: Two hundred and one patients performed before and 3 months after maximal tolerated doses of bisoprolol have been reached, a clinical evaluation, an echocardiography, a radionuclide angiography, a cardiopulmonary exercise test and hormonal determinations. RESULTS: Mean dose of bisoprolol was 8.8 +/- 2.4 mg/d. Patients had a significant improvement in NYHA classification. Heart rate at rest decreased from 87 +/- 17 to 66 +/- 12 beats/min (P < 0.0001) without any effect on electrocardiographic parameters. Left ventricular ejection fraction improved from 31 +/- 11 to 41 +/- 13% (P < 0.0001), with a significant decrease in end-diastolic and end-systolic left ventricle diameters and volumes. Mitral profile improved. Peak VO2 increased from 16.1 +/- 5 to 16.8 +/- 5.5 ml/min/kg (P = 0.001) with a significant increase in O2 pulse (from 8.52 +/- 2.7 to 11.2 +/- 3.5 ml/min/beats, P < 0.0001). Plasma levels of A-type and of B-type natriuretic peptides and of norepinephrine significantly decreased after bisoprolol. CONCLUSIONS: Bisoprolol significantly improved left ventricle ejection fraction with a reverse remodeling of the left ventricle, a decrease in hormonal activation and a modest improvement in exercise capacity.

Adrenergic beta-Antagonists↗

[Pulmonary arterial hypertension in systemic sclerosis: definition of a screening algorithm for early detection (the ItinérAIR-Sclérodermie Study)].

PURPOSE: Pulmonary arterial hypertension (PAH) is a severe complication of scleroderma. Its prevalence varies from 5% to 35% in the literature. A systematic yearly screening is recommended for early detection and management of PAH, but no precise algorithm is yet available. METHODS: From literature analysis as well as evaluation of medical needs and practices, a multidisciplinary board of experts proposed an algorithm for the screening of PAH in scleroderma. RESULTS: This algorithm is based on a precise Doppler echocardiography methodology for the purpose of screening scleroderma patients for PAH. Patients are considered as being at high or low risk of PAH depending on the maximal tricuspid regurgitation velocity. High-risk patients undergo right heart catheterization for confirmation of the diagnosis of PAH. A French multicenter transversal observational study ("ItinérAIR Sclérodermie") will be conducted in 21 hospital centers in France and involved 100 investigators organized as multidisciplinary networks. FUTURE PROSPECTS: Final results will provide confirmation that the screening algorithm is applicable in a real world setting, as well as a better knowledge of the prevalence of PAH in the various sub-groups of scleroderma patients, of the risk profile for PAH and of the value of DLCO as a predictive factor for PAH, and will support elaboration of precise screening guidelines.

Algorithms↗

[Endothelin-1 receptor antagonists in heart failure].

Endothelin-1 is a vasoconstrictor peptide playing an important role in the pathophysiology of heart failure. Endothelin-1 acts after fixation to 2 specific receptors: type A, responsible for vasoconstriction and type B, at the start of transient vasodilation and participating in clearance of the hormone. The experimental results in various animal models have demonstrated beneficial haemodynamic and clinical effects of the mixed or specific antagonists of the type A receptor. The preliminary results of studies conducted in man have confirmed the beneficial haemodynamic effects with lowering of pulmonary pressures, lowering of vascular resistance, and increase in cardiac output. On the other hand, the results of clinical studies have been disappointing, with a neutral effect of an oral mixed antagonist, bosentan, compared to placebo in the only study of morbidity and mortality. These results have put a brake on the development of this therapeutic class in heart failure.

Animals↗

[Vasopressin antagonists].

Vasopressin, like all the other neuro-hormonal systems, is activated in patients with cardiac insufficiency. Vasopressin attaches itself to two distinct specific receptors. It is through the intermediary of the renal V2 receptor, controlling the reabsorption of water by the collecting duct, that vasopressin finely regulates the blood osmolarity. The ubiquitous V1a receptor is essentially responsible for the vasoconstrictor effect of the hormone. Some specific antagonists for these two receptors have now been evaluated in various pathologies such as SIADH, cirrhosis or cardiac insufficiency. In this situation the mixed antagonists, anti-V1a-V2, seem more appropriate than the specific V1a or V2 receptor antagonists. The results of the first human studies are encouraging. The mixed antagonists reduce the pulmonary capillary pressure and increase diuresis and clearance of free water. But further studies are necessary to confirm these results and to demonstrate a reduction in morbidity and mortality before adding this class of medication to the therapeutic arsenal for our patients with cardiac insufficiency.

Antidiuretic Hormone Receptor Antagonists↗

Anterior chordal transection impairs not only regional left ventricular function but also regional right ventricular function in mitral regurgitation.

BACKGROUND: Preservation of annuloventricular continuity through the chordae tendinae aims to maintain left ventricular (LV) function and thus improve postoperative prognosis. This study was designed to prospectively investigate the effect of anterior chordal transection on global and regional LV and right ventricular (RV) function in mitral regurgitation (MR). METHODS AND RESULTS: Sixty-five patients with severe MR underwent radionuclide angiography before and after either mitral valve (MV) repair (42 patients) or replacement with anterior chordal transection (23 patients). LV and RV ejection fractions (EF) were determined at rest. Both ventricles were divided into 9 regions to analyze regional EF and the effect of anteromedial translation related to surgery. After surgery there was a significant decrease in LVEF (P=0.038) and an increase in RVEF (P=0.036). However, LVEF did not change after MV repair (63.8+/-9.9% to 62.6+/-10.3%), whereas RVEF improved (40.7+/-10.1% to 44.5+/-8.1%, P=0.027). In contrast, LVEF decreased after MV replacement (61.7+/-10.1% to 57.2+/-9.9%, P=0.03), and RVEF was unchanged (40.9+/-10.9% to 41.3+/-9.1%). LVEF 4 and 5, in the area of anterior papillary muscle insertion, were impaired after MV replacement compared with MV repair (region 4, 77.6+/-16.7% versus 87.7+/-10.8%, P=0.005, and region 5, 73.9+/-19.3% versus 89.9+/-13.1%, P<0.001). Moreover, anterior chordal transection led to a significant impairment in the apicoseptal region of the RV (RVEF 4, 50.3+/-15.6% versus 59.3+/-13.8%, P=0.02). CONCLUSIONS: Anterior chordal transection during MV replacement for MR impairs not only regional LV function but also regional RV function.

Cardiac Surgical Procedures↗

Association between anticardiolipin antibodies and mortality in patients with peripheral arterial disease.

PURPOSE: Anticardiolipin antibodies may be associated with recurrent thromboembolic events in patients with myocardial infarction or stroke. We sought to determine the prevalence of anticardiolipin antibodies in patients with peripheral arterial disease and their association with subsequent thromboembolic events and mortality. METHODS: We ascertained anticardiolipin antibodies using a standardized enzyme-linked immunosorbent assay (immunoglobulin G [IgG] anticardiolipin > or =15 GPL units or IgM anticardiolipin > or =15 MPL units) in 232 patients with peripheral arterial disease and 100 control subjects. Patients were observed to determine overall and cardiovascular mortality, and incident thromboembolic events. RESULTS: IgG anticardiolipin antibodies were significantly more common in the patients with peripheral arterial disease (36 of 232 [16%]) than in the controls (7 of 100 [7%], P = 0.03). During a median follow-up of 3.5 years, 3 of the 232 patients were lost to follow-up and 56 (24%) died. Overall mortality was significantly greater in the IgG anticardiolipin-positive patients (16 of 35 [46%]) compared with those who were IgG anticardiolipin-negative (40 of 194 [21%], P = 0.0003), largely due to an increase in cardiovascular mortality among the IgG anticardiolipin-positive patients. In a multivariate proportional hazards analysis, IgG anticardiolipin antibodies were an independent risk factor for overall mortality (hazard ratio [HR] = 2.1, 95% confidence interval [CI]: 1.2 to 4.0) and cardiovascular mortality (HR = 4.4, 95% CI: 1.6 to 12). CONCLUSIONS: IgG anticardiolipin antibodies are common in patients with peripheral arterial disease and are associated with an increased risk of overall and cardiovascular mortality.

Aged↗

Effect of mitral valve surgery on exercise capacity, ventricular ejection fraction and neurohormonal activation in patients with severe mitral regurgitation.

OBJECTIVES: The purpose of this study was to prospectively investigate the effects of surgical correction of mitral regurgitation (MR) on exercise performance, cardiac function and neurohormonal activation. BACKGROUND: Little is known about the effect of surgical correction of MR on functional status or on neurohormonal activation. METHODS: Cardiopulmonary exercise test, radionuclide angiography and blood samples for assessment of neurohormonal status were obtained in 40 patients with nonischemic MR before and within one year (216+/-80 days) after surgery. Twenty-four patients underwent mitral valve repair (MVr), and 16 underwent valve replacement (VR) with anterior chordal transection. RESULTS: Despite an improvement in New York Heart Association functional class, exercise performance did not change (peak oxygen consumption: 19.3+/-6.1 to 18.5+/-5.6 ml/kg/min, percentage of maximal predicted oxygen consumption: 79.5+/-18.2% to 76.8+/-16.9%). After surgery, left ventricular (LV) ejection fraction (EF) decreased (64.2+/-10.3% to 59.9+/-11.4%, p = 0.003) while right ventricular (RV) EF increased (41.4+/-9.6% to 44.7+/-9.5%, p = 0.03). Left ventricular EF did not change after MVr (64.3+/-11.5% to 61.5+/-12.2%), but RVEF improved (40.4+/-9.2% to 46.0+/-10.0%, p = 0.02). In contrast, VR was associated with an impairment of LV function in the apicolateral area and a decrease in LVEF (64.1+/-8.5% to 57.4+/-10.0%, p = 0.01), whereas RVEF did not change (42.9+/-10.3% to 42.8+/-8.6%). Moreover, there was only a slight decrease in neurohormonal activation after surgery. CONCLUSIONS: Despite an improvement in symptomatic status, exercise performance was not improved seven months after either MVr or VR for MR, and neurohormonal activation persisted. Compared with MVr, VR resulted in a significant impairment of cardiac function in this study.

Aged↗

[Aspirin, angiotensin converting enzyme inhibitors and cardiac insufficiency].

The possible negative therapeutic interaction between aspirin and angiotensin converting enzyme inhibitors arose from the conclusions of several experimental studies and retrospective analysis of large scale mortality trials with converting enzyme inhibitors. Some experimental results show inhibition of the vasodilatation of converting enzyme inhibitors, increase in pulmonary pressures, vascular resistances and blood pressure, and degradation of renal function and exercise capacity. However, other studies did not confirm these results. In large scale therapeutic trials, some retrospective analyses, but not all of them, have shown less benefit on morbi-mortality of converting enzyme inhibitors in patients on aspirin. The differences between the doses of aspirin, the type and dosage of the converting enzyme inhibitors and neuro-hormonal activation of the patients could explain the discordant results. The results of randomised trials are awaited but, in the meantime, it is logical to propose small doses of aspirin (< or = 100 mg/day) for patients with cardiac failure and atherosclerosis and to avoid the association in all the other patients.

Angiotensin-Converting Enzyme Inhibitors↗

[Effect of resection of the anterior chordae on cardiac function after surgical correction of mitral valve insufficiency].

The preservation of cardiac function in surgical correction of mitral regurgitation implies partially or totally preserving the subvalvular apparatus. However, the conservation of the whole subvalvular apparatus during mitral valve replacement is technically difficult as the anatomical conditions are not always favourable. In order to determine the consequences of isolated resection of the anterior chordae, the authors studied global and segmental cardiac function by isotopic angiocardiography after mitral valve repair (n = 23) or replacement with conservation of the posterior chordae (n = 16) in 39 patients with isolated, non-ischaemic mitral regurgitation. The left ventricular ejection fraction decreased after valve replacement (64.1 +/- 8.5% to 57.4 +/- 10%, p = 0.01) but not after mitral valve repair (65 +/- 11.3% to 62.1 +/- 12.2%, p = NS). The ejection fractions of segments 4 and 5, corresponding to the zones of insertion of the anterior papillary muscle, decreased after valve replacement compared with repair (segment 4: -9 +/- 13.7 versus +2 +/- 11.3, p = 0.01) (segment 5: -15 +/- 13.2 versus 2 +/- 11.7, p = 0.003). The right ventricular ejection fraction improved after valve repair (40.9 +/- 9.1% to 46.4 +/- 10.1%, p = 0.03), whereas it remained unchanged after valve replacement (42.9 +/- 10.3% to 42.8 +/- 8.6%, p = NS). These results indicate a deleterious effect of isolated resection of the anterior chordae on cardiac function during mitral valve replacement with localised abnormalities of left ventricular function. This study supports the rationale of mitral valve repair or conservation of the anterior and posterior chordae during valve replacement for isolated mitral regurgitation.

Heart Function Tests↗

Right ventricular ejection fraction is an independent predictor of survival in patients with moderate heart failure.

OBJECTIVES: We sought to study the relationship between survival and right ventricular ejection fraction (RVEF) in a subgroup of patients with moderate congestive heart failure (CHF). BACKGROUND: It has been demonstrated that RVEF is an independent predictor of survival in patients with advanced CHF. METHODS: Cardiopulmonary exercise testing and radionuclide angiography (to determine right and left ventricular ejection fraction) were prospectively performed in 205 consecutive patients with moderate CHF (140 patients in New York Heart Association [NYHA] class II, 65 in class III). RESULTS: Left ventricular ejection fraction was 29.3%+/-10.1%, RVEF was 37.5%+/-14.6% and peak oxygen consumption (VO2) was 16.2+/-5.4 ml/min/kg (60.2%+/-19% of maximal predicted VO2). After a median follow-up period of 755 days, there were 44 cardiac-related deaths, 3 deaths from noncardiac causes and 15 transplantations of whom 2 were urgent; 1 patient was lost to follow-up. Multivariate analysis showed that three variables-NYHA classification, percent of maximal predicted VO2 and RVEF-were independent predictors of both survival and event-free cardiac survival. Left ventricular ejection fraction and peak VO2 normalized to body weight had no predictive value. The event-free survival rates from cardiovascular mortality and urgent transplantation at 1 year were 80%, 90% and 95% in patients with an RVEF <25%, with a RVEF > or =25% and <35% and with a RVEF > or =35%, respectively. At 2 years, survival rates were 59%, 77% and 93% in the same subgroups, respectively. CONCLUSIONS: In addition to the NYHA classification and to the percent of maximal predicted VO2, RVEF is an independent predictor of survival in patients with moderate CHF.

Disease-Free Survival↗

Incidence and prognosis of embolic events and metastatic infections in infective endocarditis.

AIMS: In infective endocarditis, the true incidence of embolic events and metastatic infections remains unknown probably because a large number of events are asymptomatic. The consequences of the prognosis of such events have never been evaluated by a prospective follow-up. This study aimed to assess the incidence of symptomatic or asymptomatic embolic events and metastatic infections in definite infective endocarditis and to determine whether these events carry a risk of mortality. METHODS AND RESULTS: From January 1991 to December 1993, 102 patients with suspected or known infective endocarditis were referred to our institution. Among them, we selected 68 patients (50 males, 18 females, mean age = 52.7 years) exhibiting definite infective endocarditis according to the Duke University criteria. Blood cultures were positive in 49 cases (72%). Echocardiography revealed valvular vegetations in 55 cases (81%). Irrespective of the clinical presentation, patients were examined radiologically by cerebral computed tomography scanning (n = 60), magnetic resonance imaging (n = 3), abdominal computed tomography scanning (n = 32) or abdominal echocardiography (n = 20). Depending on the symptoms, thoracic computed tomography scanning (n = 22), pulmonary angiography (n = 2), ventilation-perfusion scintigraphy (n = 4), or gallium citrate radionuclide scanning (n = 7) were also performed. All patients were prospectively followed-up for a mean period of 21.4 +/- 17.5 months. In 35 patients (51%), 51 embolic or metastatic events were revealed, involving the central nervous system (n = 23), spleen (n = 7), kidney (n = 5), lung (n = 5), liver (n = 4), bone and joint (n = 4), iliac (n = 2) or mesenteric (n = 1) arteries. During the hospital stay, the mortality rate was higher in patients exhibiting embolic or metastatic events (20 vs 12%), but the difference did not reach statistical significance. Kaplan-Meier analysis demonstrated no difference in long-term follow-up. CONCLUSION: Our data suggest that embolic or metastatic events had a high incidence (51%) during infective endocarditis, but were not associated with significant attributable mortality.

Adult↗

[Coronary angioscopy].

Coronary angioscopy evaluates the composition of the atherosclerotic plaque by direct examination of the arterial wall. The angioscope is fitted with a balloon which prevents assessment of the proximal segment of the vessels. The fibre optic system provides and excellent view of the mid and distal segments of the coronary arteries. The coronary arteries appear smooth and white on angioscopy. The atherosclerotic plaque is a white or yellowish incursion. Unstable plaques are characterised by the presence of thrombus. In unstable angina, thrombus is observed in 64% of cases and in 75% of cases during the first month after myocardial infarction. The colour of the plaque seems to be related to its fragility: the yellow plaque is much more common during myocardial infarction than in unstable angina (75% versus 47% of cases). Finally, after coronary angioplasty restenosis is more commonly white, covered by neo-intimal proliferation. Angioscopy has been shown to be feasible and safe and it is a better method of identifying thrombus. At present, it is a tool for clinical research in coronary thrombosis and interventional cardiology.

Angioplasty, Balloon, Coronary↗

Plasma levels of atrial natriuretic peptide at peak exercise: a prognostic marker of cardiovascular-related death and heart transplantation in patients with moderate congestive heart failure.

BACKGROUND: Conflicting data have been published concerning exercise performance and hormonal activation. Previous studies have demonstrated the prognostic information of plasma levels of neurohormones at rest in patients with congestive heart failure. No study has examined the prognostic information of plasma levels of hormones at peak exercise. METHODS: Fifty-five consecutive ambulatory patients with stable moderate congestive heart failure (New York Heart Association class II to III) performed a maximal symptom limited cardiopulmonary exercise test with the determination of peak oxygen consumption. Blood samples were drawn at rest and at peak exercise for the determination of plasma levels of atrial natriuretic peptide, aldosterone, and plasma renin activity. RESULTS: Hormonal activation was present at rest, and exercise significantly increased hormonal values. There was no correlation between exercise parameters and hormonal values either at rest or at peak exercise. After a median follow-up period of 724 days, in univariate and multivariate Cox analysis, the most significant independent prognostic marker was the plasma level of atrial natriuretic peptide at peak exercise. Patients with a plasma level of atrial natriuretic peptide > 38 pmol/L had an event rate of 48% compared with an event rate of 14.8% in the other subgroup (p < 0.01). CONCLUSIONS: In patients with stable moderate congestive heart failure, exercise increased hormonal values, but there was no relationship between hormonal activation and exercise performance. Plasma level of atrial natriuretic peptide at peak exercise was the most significant independent marker of cardiovascular-related death and of cardiovascular-related death and heart transplantation.

Adult↗

Pericardioscopy in the etiologic diagnosis of pericardial effusion in 141 consecutive patients.

BACKGROUND: Although previous small series have documented the utility of pericardioscopy for accurate etiologic diagnosis of pericardial effusion, this technique remains underused. The aim of our study was to assess the benefits and risks of surgical pericardioscopy in a large prospective series. METHODS AND RESULTS: One hundred forty-one consecutive patients with unexplained pericardial effusion underwent 142 pericardioscopies with a rigid mediastinoscope. For each patient, the etiologic data obtained by pericardioscopy (visualization of pericardium, guided biopsies, subxiphoid window biopsy, and fluid analysis) were compared with the results that would have been obtained with only conventional surgical drainage and biopsy (subxiphoid window biopsy and fluid analysis). After complete workup, a specific cause was found in 69 cases (48.6%); the other 73 cases were considered idiopathic effusions (51.4%). Procedural and in-hospital mortality was 8 of 141 patients (5.6%). No death was directly attributable to pericardioscopy. During long-term follow-up (median duration, 24 months; range, 6 to 96), a previously unrecognized cause was discovered in 6 patients (4%). By comparing the areas under the receiver-operating characteristic curves, the diagnostic advantage of pericardioscopy was significant for the whole series (pericardioscopy, 0.98 +/- 0.011; conventional surgical drainage, 0.89 +/- 0.029; P < .001). The increase in sensitivity was more marked for some types such as neoplastic (21%), radiation-induced (100%), or purulent (83%) effusions. CONCLUSIONS: Our data demonstrate that pericardioscopy increases the diagnostic sensitivity of surgical pericardial drainage and biopsy without specific risk.

Adolescent↗

Usefulness of diltiazem in the acute management of supraventricular tachyarrhythmias in the elderly.

Acute management of supraventricular tachyarrhythmias is often difficult in elderly patients. Diltiazem was given intravenously (loading dose of 0.25 mg/kg over 2 minutes followed by a 4 mg/kg/24 hr infusion) in 37 elderly patients (mean age 70 years, range 60-91). Fifteen out of the 37 patients (41%) had left ventricular cardiac disease, 12 (32%) had cor pulmonale, and 10 (27%) had no obvious cardiac disease. Hemodynamic tolerance of the supraventricular tachyarrhythmia was poor in 12 patients. A good result was defined as a return to sinus rhythm after bolus or infusion, or as a slowing of the ventricular rate (VR) to less than 100 beats/min. Of the 23 patients in atrial fibrillation, about half reverted to sinus rhythm after diltiazem, and in most of the others the ventricular rate decreased to less than 100 beats/min. Side effects occurred in 10 patients (bradycardia in 6, cutaneous rash in 2, hypotension in 2). They rapidly reversed after cessation of diltiazem. They were responsible for 2 out of the 5 poor results. Thus, diltiazem appeared effective and safe when used carefully in elderly patients with supraventricular tachyarrhythmia.

Aged↗