Mitral regurgitation: when to intervene? : A historical perspective.

Although mitral regurgitation (MR) is the most common valvular heart disease, it should be regarded as a complex multifactorial disease that involves multiple entities. Optimal medical therapy alone does not hinder the progression of the disease, and in the 1980s it was already recognised that corrective surgery is indicated if MR is severe and patients are symptomatic (except for those with the most severe left ventricle dysfunction). Later on, asymptomatic patients with deterioration of the left ventricular ejection fraction were also operated on to avoid irreversible left ventricular dysfunction, heart failure and eventually death. However, a major drawback remains the fact that a significant group of patients is considered to have a high perioperative risk due to their advanced age or severe comorbidities. Since less invasive, percutaneous interventions have been developed and recently thoroughly investigated in the MITRA-FR and the COAPT studies, the type of intervention and also the timing have become more crucial. In this critical review of the literature, we describe what we should have learned from the past and which (haemodynamic) parameters can best predict the outcome in patients with MR.

Antithrombotic therapy in patients undergoing TAVI: an overview of Dutch hospitals.

PURPOSE: To assess current antithrombotic treatment strategies in the Netherlands in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: For every Dutch hospital performing TAVI (n = 14) an interventional cardiologist experienced in performing TAVI was interviewed concerning heparin, aspirin, thienopyridine and oral anticoagulation treatment in patients undergoing TAVI. RESULTS: The response rate was 100 %. In every centre, a protocol for antithrombotic treatment after TAVI was available. Aspirin was prescribed in all centres, concomitant clopidogrel was prescribed 13 of the 14 centres. Duration of concomitant clopidogrel was 3 months in over two-thirds of cases. In 2 centres, duration of concomitant clopidogrel was based upon type of prosthesis: 6 months versus 3 months for supra-annular and intra-annular prostheses, respectively. CONCLUSIONS: Leaning on a small basis of evidence and recommendations, the antithrombotic policy for patients undergoing TAVI is highly variable in the Netherlands. As a standardised regimen might further reduce haemorrhagic complications, large randomised clinical trials may help to establish the most appropriate approach.

Life-threatening bilateral aorto-ostial coronary artery disease in an octogenarian.

Aorto-ostial disease is difficult to approach percutaneously; therefore, a surgical option may be more desirable. We describe a case of an octogenarian in which the clinical arguments and technical approach have been summarised for a successful percutaneous therapeutic strategy. (Neth Heart J 2009;17:30-2.).

Closure of the femoral artery after cardiac catheterization: a comparison of Angio-Seal, StarClose, and manual compression.

OBJECTIVES: To compare Angio-Seal (AS) and StarClose (SC) and manual compression (MC) on efficacy of hemostasis, complication rate, safety of early mobilization, and patient comfort. BACKGROUND: Closure of the femoral artery after cardiac catheterization can be obtained through different methods. Today, physicians can choose from a number of different devices to achieve arterial closure. METHODS: In a prospective trial 450 patients were randomized to AS, SC, or MC. Patients were mobilized 1 to 2 hr after device placement, and 6 hr after MC. Data were collected during hospital admission and by telephone at one month after hospital discharge. RESULTS: Devices were used in 138/150 allocated to AS and 124/150 allocated to SC patients (92% vs. 83%, P = 0.015) Patients with MC experienced more pain during sheath removal than patients receiving a device, and rated their period of bed rest as less comfortable. Oozing and need for pressure bandage at the puncture site were observed in 37 AS patients and 57 SC patients (25% vs. 38%, P = 0.002). Hematoma occurred in 15 AS patients, in 17 SC patients, and in 14 MC patients (11 vs. 14 vs. 9%, ns). CONCLUSION: There is no difference in safety between the three methods of arterial closure. SC was more often not used or successfully deployed. SC patients more often had continuing oozing. On patient comfort, closure devices performed better than MC. Early ambulation in patients with a closure device is safe. AS is the preferred method of arterial closure after cardiac catheterization.

Visualization of anomalous coronary arteries on dual-source computed tomography.

The purpose of this study is to assess the capability of dual-source computed tomography (DSCT) in evaluating coronary artery anomalies. Early detection and evaluation of coronary artery anomalies is essential because of their potential association with myocardial ischemia and sudden death. In 16 patients (12 men, mean age 50 +/- 14 years), anomalous coronary arteries were detected on contrast-enhanced DSCT in a patient cohort of 230 individuals (incidence of 7%). Six different types of anomalies were diagnosed (three fistula, four anomalies of the circumflex artery, four anomalous right coronary arteries, three anomalies of the left coronary artery, one absent left main coronary artery, and one left coronary artery arising from the pulmonary trunk). Of the 16 patients, 10 also underwent conventional coronary angiography (CAG). Retrospective evaluation of the CAGs by an experienced interventional cardiologist resulted in a precise diagnosis in 50% of patients. With DSCT, sufficient image quality and exact visualization of the aberrant anatomy were achieved in all patients. Therefore, DSCT seems to be an accurate diagnostic tool for examining the precise origin, course, and shape of aberrant coronary arteries.

Haemodynamic patterns in ST-elevation myocardial infarction: incidence and correlates of elevated filling pressures.

OBJECTIVES.: We sought to study the incidence and clinical correlates of elevated filling pressures in ST-elevation myocardial infarction (STEMI) patients, without physical signs of heart failure and treated with primary coronary angioplasty. BACKGROUND.: Haemodynamic data, as measured with a Swan-Ganz catheter, are not routinely obtained in STEMI patients. At admission, low blood pressure, increased heart rate, sweating, increased respiration rate, rales, oedema, and a third heart sound are indicative of heart failure. METHODS.: All consecutive STEMI patients were monitored by a Swan-Ganz catheter and central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure (PAS) and cardiac index (CI) were measured. To investigate the clinical correlates of the haemodynamic status patients were classified according to previously defined haemodynamic criteria. RESULTS.: We studied 90 patients, aged 60.5+/-13.1 year, 76% were male. Mortality at 30 days was 2/90 (2.2%). Patients with impaired haemodynamics presented later and had larger myocardial infarct sizes. CVP, PCWP and PAS were above normal in 36 (40%) patients. CONCLUSION.: A large proportion of STEMI patients without physical signs of heart failure have elevation of right- as well as left-sided cardiac filling pressures. (Neth Heart J 2007;15:95-9.).

Aortic dissection presenting as acute myocardial infarction: potential harm of antithrombin and antiplatelet therapy.

In the treatment of acute myocardial infarction, antithrombin and antiplatelet therapy are indicated according to the current guidelines. When a patient presents with symptoms and signs of acute myocardial infarction, an extensive list of diagnoses should be considered. Because of the nonspecific symptoms of aortic dissection, the disease may be easily misdiagnosed. A high clinical suspicion of aortic dissection is therefore required. Once aortic dissection has been diagnosed, surgical intervention provides the only definitive treatment for these patients, regardless of antithrombin and antiplatelet therapy.

Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade.

OBJECTIVES: We sought to study the effect of angiotensin-converting enzyme inhibition on exercise-induced myocardial ischemia. BACKGROUND: Although angiotensin-converting enzyme inhibitors have been shown to reduce ischemic events after myocardial infarction, few data are available regarding their direct anti-ischemic effects in patients with coronary artery disease. METHODS: We studied 43 patients (average age 63 +/- 8 years) with exercise-induced myocardial ischemia (> or =0.1 mV ST depression, despite optimal beta blockade) and normal left ventricular function (ejection fraction >0.50). In a double-blind, placebo-controlled parallel design, patients were treated with angiotensin-converting enzyme inhibitor (enalapril 10 mg twice daily) or placebo. Assessments were made after three weeks (short-term) and 12 weeks (long-term). RESULTS: At baseline, the groups were well matched for all clinical characteristics. After three weeks, there was a slight but not significant increase in time to 0.1 mV ST depression in both groups (p = NS); rate pressure product (RPP = heart rate x systolic blood pressure) was also unaffected. After 12 weeks, however, time to 0.1 mV ST depression further increased in the enalapril group (5.6 +/- 1.9 min) but was unchanged in the placebo group (4.4 +/- 1.3 min; p < 0.05 between groups). In contrast, RPP was not affected. Concentrations of both atrial and brain natriuretic peptides at peak exercise tended to be lower by enalapril, if compared to placebo (p = NS). CONCLUSIONS: Angiotensin-converting enzyme inhibition may reduce exercise-induced myocardial ischemia in patients with normal left ventricular function. Further studies are needed to elucidate the mechanisms involved.

Long-term anti-ischemic effects of angiotensin-converting enzyme inhibition in patients after myocardial infarction. The Captopril and Thrombolysis Study (CATS) Investigators.

OBJECTIVES: This study was conducted to test the hypothesis that angiotensin-converting enzyme (ACE) inhibition reduces myocardial ischemia and related events after myocardial infarction (MI). BACKGROUND: The oxygen demand/supply ratio of the myocardium is influenced by angiotensin II as a result of its arterial vasoconstrictive and inotropic effects and through its interaction with the sympathetic nervous system. METHODS: We studied 244 patients who had been included in a double-blind, randomized, placebo-controlled, post-MI, ACE inhibition intervention study (Captopril and Thrombolysis Study [CATS]). All patients underwent exercise testing before and 3 and 12 months after hospital discharge. After 1-year double-blind treatment, all patients continued receiving single-blind placebo for 1 month. RESULTS: Total exercise time increased in both groups after 3 months (placebo: +86 +/- 13 s; captopril: +69 +/- 12 s, p = 0.8 between groups) and increased further after 1 year (placebo: +13 +/- 11 s; captopril: +33 +/- 13 s, p = 0.7 between groups). There were also no differences in mean ST segment depression. During the 12 months, significantly fewer ischemia-related events occurred in the captopril group (82 vs. 52, p = 0.015). This difference was found between 3 and 12 months but not during the first 3 months. After withdrawal from double-blind medication, nine ischemic events were reported in teh captopril group compared with one in the placebo group (p = 0.006 between groups). CONCLUSIONS: The present data show that captopril may reduce the incidence of ischemia-related events after MI, which becomes apparent after 3 months. However, no anti-ischemic effect was observed during exercise testing. After withdrawal from ACE inhibition, a high incidence of clinical events occurred, suggesting a rebound phenomenon.

Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: We performed positron emission tomography (PET) to evaluate myocardial ischemia in patients with idiopathic dilated cardiomyopathy (IDC). BACKGROUND: Patients with IDC have anatomically normal coronary arteries, and it has been assumed that myocardial ischemia does not occur. METHODS: We studied 22 patients with IDC and 22 control subjects using PET with nitrogen-13 ammonia to measure myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia. To investigate glucose metabolism, fluorine-18 deoxyglucose (18FDG) was used. For imaging of oxygen consumption, carbon-11 acetate clearance rate constants (k(mono)) were assessed at rest and during submaximal dobutamine infusion (20 microg/kg body weight per min). RESULTS: Global MBF reserve (dipyridamole-induced) was impaired in patients with IDC versus control subjects (1.7 +/- 0.21 vs. 2.7 +/- 0.10, p < 0.05). In patients with IDC, MBF reserve correlated with left ventricular (LV) systolic wall stress (r = -0.61, p = 0.01). Furthermore, in 16 of 22 patients with IDC (derived by dipyridamole perfusion) mismatch (decreased flow/increased 18FDG uptake) was observed in 17 +/- 8% of the myocardium. The extent of mismatch correlated with LV systolic wall stress (r = 0.64, p = 0.02). The MBF reserve was lower in the mismatch regions than in the normal regions (1.58 +/- 0.13 vs. 1.90 +/- 0.18, p < 0.05). During dobutamine infusion k(mono) was higher in the mismatch regions than in the normal regions (0.104 +/- 0.017 vs. 0.087 +/- 0.016 min(-1), p < 0.05). In the mismatch regions 18FDG uptake correlated negatively with rest k(mono) (r = -0.65, p < 0.05), suggesting a switch from aerobic to anaerobic metabolism. CONCLUSIONS: Patients with IDC have a decreased MBF reserve. In addition, low MBF reserve was paralleled by high LV systolic wall stress. These global observations were associated with substantial myocardial mismatch areas showing the lowest MBF reserves. In geographically identical regions an abnormal oxygen consumption pattern was seen together with a switch from aerobic to anaerobic metabolism. These data support the notion that regional myocardial ischemia plays a role in IDC.

Evaluation of haemodynamics by cardiac catheterisation: historical perspective and present practice.

In 1956, three men were awarded the Nobel Prize in Physiology or Medicine, in particular 'for their discoveries concerning heart catheterisation and pathological changes in the circulatory system'. Their names in alphabetical order: André F. Cournand, Werner Forssmann and Dickinson W. Richards. Forssmann's experiment dated from 1929, while Cournand and Richards started their work in 1941. The order in which they presented their Nobel lectures on 11 December 1956 was Forssmann, Richards, Cournand.

Comparison between felodipine and isosorbide mononitrate as adjunct to beta blockade in patients > 65 years of age with angina pectoris.

Coronary artery disease is an increasingly common medical problem in the elderly, and relatively few studies investigating drug therapy focus on this population. To assess the efficacy and safety of the calcium channel blocker, felodipine, and isosorbide mononitrate (ISMN), as adjunct to optimal beta-blocker therapy in elderly patients, a placebo-controlled, double-blind study was conducted in 46 patients, aged between 65 and 80 years, with documented stress-induced angina pectoris and myocardial ischemia. With use of a latin-square design, with 3 periods of 4 weeks each, exercise testing was performed after each period. Felodipine, 5 mg once daily, significantly improved both time to ischemic threshold and pain threshold (p = 0.02 and p = 0.003, respectively, vs placebo), and tended to increase total exercise time (p = 0.06 vs placebo). In contrast, ISMN, 20 mg twice daily, did not significantly affect these parameters. Comparison of the 2 active treatment arms showed that, overall, felodipine was more effective than ISMN, with a statistically significant difference for time to ischemic threshold (p = 0.02). With regard to safety, felodipine was also better tolerated than ISMN, which led to more patients discontinuing study medication with ISMN (p < 0.05 between ISMN and felodipine). It is concluded that in elderly patients who are treated with optimal beta blockade, felodipine, but not ISMN, leads to an additional significant reduction in ischemic parameters during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Nifedipine gastrointestinal therapeutic system versus atenolol in stable angina pectoris. The Netherlands Working Group on Cardiovascular Research (WCN).

The gastrointestinal therapeutic system formulation of nifedipine enables a once-daily dosing resulting in predictable, relatively constant plasma concentrations. To evaluate the efficacy and safety of this formulation and to compare this with the beta-blocker atenolol, we conducted a double-blind, randomised, multi-centre study in 129 male patients with documented exercise induced angina pectoris. After 4 weeks' treatment, nifedipine (60 mg), improved time to onset of 0.1 mV ST-segment depression from 536 s by 72 +/- 117s, time to onset of pain from 619 s by 56 +/- 120 s, and total exercise time from 685 s by 40 +/- 88 s. Atenolol 100 mg, had a comparable effect, time to onset of 0.1 mV ST-segment depression improved from 496 s by 53 +/- 129 s, time to onset of pain from 572 s by 57 +/- 118 s, and total exercise time from 653 s by 33 +/- 99 s. Between group analysis revealed no statistically significant differences for these exercise parameters. Atenolol, but not nifedipine, significantly reduced heart rate and systolic blood pressure at rest and during exercise (P < 0.001 between groups), indicating different modes of action of the drugs. With regard to safety, both drugs were generally well tolerated. There were significantly (P = 0.01) more vasodilation related side effects with nifedipine. These data demonstrate that gastrointestinal therapeutic system formulation of nifedipine and atenolol as once-daily monotherapy are equally effective and safe, but with different effects on exercise parameters.

Validation of Fick cardiac output calculated with assumed oxygen consumption: a study of cardiac output during epoprostenol.

OBJECTIVE: To test the validity of using assumed oxygen consumption for Fick cardiac output during administration of epoprostenol. METHODS: In 24 consecutive patients Fick cardiac output calculated with assumed oxygen consumption according to LaFarge and Miettinen (COLM) and according to Bergstra et al. (COBE) were compared with thermodilution cardiac output (COTH). Pulmonary vascular resistance (PVR) was calculated with each cardiac output (CO) value. If PVR exceeded 200 dyne.s.cm-5, administration of epoprostenol (Ep) was started, and at maximal dose the above-mentioned measurements were repeated. RESULTS: In all 24 patients COBE agreed significantly with COTH, mean difference -0.145 1.min-1, 95% confidence interval (CI) -0.402 to 0.111, limits of agreement (LA) -1.336 to 1.045. COLM was significantly lower than COTH, -1.165 1.min-1, p<0.05, 95% CI -1.510 to -0.819, LA -2.768 to 0.438. In 16 patients (67%) administration of epoprostenol was indicated. During Ep infusion the CO values calculated with oxygen consumption according to LaFarge and Miettinen (EpCOLM) were also significantly lower than thermodilution CO (EpCOTH), mean difference -1.281 1.min-1, p<0.05, 95% CI -1.663 to -0.900, LA -2.685 to 0.122. The agreement of CO values calculated with oxygen consumption according to Bergstra et al. (EpCOBE) and EpCOTH remained, mean difference -0.115 1.min-1, 95% CI -0.408 to 0.178, LA -1.191 to 0.962. CONCLUSION: Before as well as during administration of epoprostenol, it is justified to use CO values calculated with oxygen consumption according to Bergstra et al. instead of thermodilution CO; CO values calculated with oxygen consumption according to LaFarge and Miettinen show significant underestimation.

Planning and monitoring of patients for electrical cardioversion for atrial fibrillation.

OBJECTIVES: This study evaluated the waiting list for elective electrical cardioversion (ECV) for persistent atrial fibrillation (AF), focusing on when and why procedures were postponed. We compared the effects of management of the waiting list conducted by physicians versus management by nurse practitioners (NPs) and we evaluated the safety of our anticoagulating policy by means of bleeding or thromboembolic complications during and after ECV. BACKGROUND: Not all patients selected for ECV receive their treatment at the first planned instance due to a variety of reasons. These reasons are still undocumented. METHODS: We evaluated 250 consecutive patients with persistent AF admitted to our clinic for elective ECV. RESULTS: Within 5 to 6 weeks, 186 of 242 patients (77%) received ECV. The main reason for postponing an ECV was an inadequate international normalised ratio (INR); other reasons included spontaneous sinus rhythm and switch to rate control. A total of 23 of the 147 patients (16%) managed by the research physician were postponed due to an inadequate INR at admission versus 4 out of 98 patients (4%) managed by NPs (p = 0.005) CONCLUSION: An inadequate INR is the main reason for postponing an ECV. Management of ECV by NPs is safe and leads to less postponing on admission.

Neurohumoral response to carmoxirole, a selective dopamine (D2) receptor agonist, in patients with chronic moderate heart failure.

Neurohormonal activation and elevated ventricular filling pressures are prominent features in heart failure. Carmoxirole is a DA2 receptor agonist with limited central activity that modulates sympathetic activation and subsequently reduces pre-load and afterload in animals. The effect of carmoxirole on neurohormones and hemodynamics in humans was evaluated in 12 normotensive patients with NYHA class III-IV heart failure on stable ACE 1 and diuretic therapy. Carmoxirole (0.25-1.00 mg) was administered on 2 consecutive days, and hemodynamic and neurohormonal measurements were carried out. Values given are maximal percent changes from prestudy baseline (significance level P < 0.05). The lower dose on day 1 (0.25-0.50 mg) reduced circulating norepinephrine, vasopressin, and ANP by 40%, 19%, and 25%, respectively. In addition, on day 2, at a dose level of 0.75-1.00 mg, plasma renin activity decreased by 30%. Mean arterial pressure and systemic vascular resistance were reduced by 10% and 18%, and pulmonary wedge and right atrial pressure by 38% and 39%, respectively. Cardiac index improved by 20%. Despite a concomitant 12% reduction in heart rate, both stroke volume and stroke work index increased by 32% and 31%, respectively. Mean pulmonary artery pressure decreased by 21%, whereas pulmonary resistance was not affected. Thus, carmoxirole modulates sympathetic activation, accompanied by changes in vasopressin and ANP, and the renin-angiotensin system at higher dosages. These effects lead to a reduction in systemic resistance and heart rate, and an improvement in cardiac pump function and left and right ventricular filling pressures. It is concluded that carmoxirole induces beneficial effects on hemodynamic and neurohumoral parameters in heart failure.