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.

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.

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.).

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.

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.

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.

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.

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.

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.

Impairment of myocardial blood flow reserve in patients with asymptomatic left ventricular dysfunction: effects of ACE-inhibition with perindopril.

Myocardial blood flow (MBF) reserve is impaired in patients with symptomatic chronic heart failure. Whether this is already present in asymptomatic left ventricular (LV) dysfunction, and whether it is affected by angiotensin converting enzyme (ACE) inhibition, is unknown. We examined MBF in 20 patients with asymptomatic LV dysfunction and compared them to healthy volunteers. MBF (reserve) was assessed with positron emission tomography (PET) and N-13 ammonia at rest, during dipyridamole stress test (DST) and during cold pressor test (CPT). Further, in the LV-dysfunction group, we studied the effects of 3 months treatment with ACE inhibition with a second PET study. Patients were randomized double-blind to perindopril 4 mg daily or placebo. MBF at rest was similar in controls and patients. DST-induced MBF reserve, however, was decreased in patients vs. controls (1.71+/-0.2 vs. 2.62+/-0.5, respectively p < 0.05). Also CPT-induced MBF was lower in patients (1.14+/-0.06 vs. 1.23+/-0.03, p < 0.05). After 3 months double-blind treatment, CPT-induced MBF decreased in the placebo group (from 1.12+/-0.02 to 0.93+/-0.06), but was preserved in the perindopril group (from 1.16+/-0.08 to 1.14+/-0.08 shifts from baseline: -0.19+/-0.05 vs. -0.02+/-0.07 respectively p = 0.07). This was compatible with a trend to a smaller increase in coronary vascular resistance during CPT (1.23+/-0.08 vs. 1.03+/-0.06, placebo vs. perindopril, p = 0.06). In patients with asymptomatic LV dysfunction, MBF, both after vasodilation and after CPT, is already impaired. ACE inhibition with perindopril during this short-term treatment had no significant effects.

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.

Differential anti-ischaemic effects of muscarinic receptor blockade in patients with obstructive coronary artery disease; impaired vs normal left ventricular function.

AIMS: In patients with coronary artery disease acetylcholine (a muscarinic agonist) causes vasoconstriction. The effect of atropine (a muscarinic antagonist) on coronary vasotone in patients with normal or impaired left ventricular function is unknown. METHODS AND RESULTS: Twenty-four patients who required atropine infusion (to supplement heart rate response) during atrial pacing (pacing was conducted to assess ischaemia as part of an experimental protocol) were studied; 17 patients had normal and seven impaired left ventricular function (ejection fraction < or =0.40). Two control groups were selected from a large database (from patients in whom atrial pacing was carried out but to whom atropine was not administered) to match the normal (n=20) and dysfunction (n=10) groups. In the normal left ventricular function group atropine increased rate pressure product by 12 +/- 4%, as compared to those without atropine (P < 0.05). Left ventricular end diastolic pressure increased less in the atropine group (+40 +/- 8% vs +78 +/- 6%;P < 0.05). Arterial norepinephrine increased similarly in both groups, but coronary flow (as assessed by using a thermodiluting method in the coronary sinus) increased 23 +/ -4% more in the atropine group (P < 0.05). Further, there were lower levels of myocardial lactate production and ST-segment depression in the atropine group [lactate extraction +13 +/- 6% (atropine) vs -19 +/- 4% (controls), ST-segment depression 1. 3 +/- 0.6 (atropine) vs 1.8 +/- 0.2 mm (control), both P < 0.05 between groups]. In contrast, in the dysfunction group the overall effect of atropine was less pronounced. CONCLUSION: In patients with normal left ventricular function atropine improves coronary flow and reduces myocardial lactate production and ST-segment depression during atrial pacing, suggesting a reduction in myocardial ischaemia.

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.

Ischemia and left ventricular dysfunction: a reciprocal relation?

There is convincing evidence that (prolonged) episodes of myocardial ischemia lead to impairment of left ventricular (LV) function and ultimately to chronic congestive heart failure (CHF), but whether the opposite is also true has not been well established. We studied this issue in two groups of CHF patients with positron emission tomography (PET) by using [13N]ammonia (13NH3) as a tracer. In the first protocol we compared 12 patients with idiopathic dilated cardiomyopathy (who have normal coronary arteries) with 12 healthy controls. In the second protocol we studied a group of 24 patients with documented coronary artery disease (CAD). In this protocol, we compared patients with normal LV function to those with LV dysfunction and CHF. In patients with cardiomyopathy, myocardial blood flow at rest was normal but flow reserve (after dipyridamole infusion) was significantly impaired (1.7 +/- 0.08) compared with normal subjects (2.7 +/- 0.04; p <0.05). Furthermore, by examining [18F]fluorodeoxyglucose (18FDG) uptake, a perfusion-metabolism mismatch was observed in 24 +/- 6% of the myocardium in patients with cardiomyopathy as opposed to 0% of normals (p <0.05). In patients with CAD, myocardial blood flow reserve (measured in non-stenotic arteries to non-infarcted area) was impaired in CHF patients (1.7 +/- 0.06) compared to those with normal LV function (2.3 +/- 0.05; p <0.05). In both groups of CHF patients, the impairment of blood flow reserve showed a significant correlation with the severity of CHF. In conclusion, myocardial blood flow reserve is impaired in patients with CHF in proportion to the degree of CHF. Metabolic studies with 18FDG further show that, in patients with idiopathic dilated cardiomyopathy and CHF, flow-metabolism mismatch is present in a substantial part of the myocardium, suggesting a pathogenetic role for ischemia.