Optimization of imaging before pulmonary vein isolation by radiofrequency ablation: breath-held ungated versus ECG/breath-gated MRA.

Isolation of the pulmonary veins has emerged as a new therapy for atrial fibrillation. Pre-procedural magnetic resonance (MR) imaging enhances safety and efficacy; moreover, it reduces radiation exposure of the patients and interventional team. The purpose of this study was to optimize the MR protocol with respect to image quality and acquisition time. In 31 patients (23-73 years), the anatomy of the pulmonary veins, left atrium and oesophagus was assessed on a 1.5-Tesla scanner with four different sequences: (1) ungated two-dimensional true fast imaging with steady precession (2D-TrueFISP), (2) ECG/breath-gated 3D-TrueFISP, (3) ungated breath-held contrast-enhanced three-dimensional turbo fast low-angle shot (CE-3D-tFLASH), and (4) ECG/breath-gated CE-3D-TrueFISP. Image quality was scored from 1 (structure not visible) to 5 (excellent visibility), and the acquisition time was monitored. The pulmonary veins and left atrium were best visualized with CE-3D-tFLASH (scores 4.50 +/- 0.52 and 4.59 +/- 0.43) and ECG/breath-gated CE-3D-TrueFISP (4.47 +/- 0.49 and 4.63 +/- 0.39). Conspicuity of the oesophagus was optimal with CE-3D-TrueFISP and 2D-TrueFISP (4.59 +/- 0.35 and 4.19 +/- 0.46) but poor with CE-3D-tFLASH (1.03 +/- 0.13) (p < 0.05). Acquisition times were shorter for 2D-TrueFISP (44 +/- 1 s) and CE-3D-tFLASH (345 +/- 113 s) compared with ECG/breath-gated 3D-TrueFISP (634 +/- 197 s) and ECG/breath-gated CE-3D-TrueFISP (636 +/- 230 s) (p < 0.05). In conclusion, an MR imaging protocol comprising CE-3D-tFLASH and 2D-TrueFISP allows assessment of the pulmonary veins, left atrium and oesophagus in less than 7 min and can be recommended for pre-procedural imaging before electric isolation of pulmonary veins.

Noninvasive evaluation of global left ventricular function with use of cine nuclear magnetic resonance.

Previous reports have validated the accuracy of nuclear magnetic resonance (NMR) imaging for quantitating ventricular volumes and myocardial mass. In this study, a new rapid NMR imaging method, cine NMR imaging, was used to compare left ventricular volumes determined from the transverse plane and short-axis plane in healthy volunteers and patients with dilated cardiomyopathy. With use of the short-axis plane, left ventricular mass at end-systole and end-diastole were determined and left ventricular systolic wall thickening at three different levels was assessed. For validation in the current study, cine NMR imaging and two-dimensional echocardiographic measurements of left ventricular volumes were correlated. Left ventricular volumes of the normal volunteers (end-systolic volume = 34 +/- 3.8 ml, end-diastolic volume = 90.4 +/- 7.2 ml) and patients with cardiomyopathy (end-systolic volume = 173 +/- 28.3 ml, end-diastolic volume = 219.5 +/- 29.6 ml) obtained in the transverse plane were nearly identical to those obtained in the short-axis plane (normal volunteers, end-systolic volume = 30.3 +/- 3.5 ml, end-diastolic volume = 84.7 +/- 7.0 ml and patients with cardiomyopathy, end-systolic volume = 179.1 +/- 27.8 ml, end-diastolic volume = 227 +/- 30.9 ml) and correlated highly (r = 0.91) with volumes obtained by two-dimensional echocardiography. Assessment of left ventricular mass over a broad range using cine NMR imaging in a short-axis plane was identical at end-systole (normal volunteers, 117 +/- 10 g; patients with cardiomyopathy, 202 +/- 20 g) and end-diastole (normal volunteers, 115 +/- 10 g; patients with cardiomyopathy, 194 +/- 21 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Bradykinin improves postischaemic recovery in the rat heart: role of high energy phosphates, nitric oxide, and prostacyclin.

OBJECTIVE: The aim was to define: (1) whether bradykinin administration during reperfusion improves postischaemic myocardial recovery; (2) whether high energy phosphate compounds are involved in the protective effects of bradykinin; and (3) whether bradykinin-induced release of prostacyclin and nitric oxide mediate the protective effects of bradykinin. METHODS: In the Langendorff rat heart preparation, coronary flow, left ventricular developed pressure, and, using 31P magnetic resonance spectroscopy, the high energy phosphate compounds phosphocreatine and beta-ATP were assessed during 15 min of global ischaemia and 30 min of reperfusion. Administration of 10(-7) M bradykinin was started before ischaemia and maintained throughout the experiment (BK-pre). This was compared to 10(-7) M bradykinin given exclusively with reperfusion (BK-post). Then 10(-7) M bradykinin was given simultaneously with 10(-4) M N omega-nitro-L-arginine-methyl ester (BK-LNAME) or 10(-5) M indomethacin (BK-indo). RESULTS: In comparison to control hearts, BK-pre exerted a significant protective effect on the postischaemic recovery of coronary flow [71(5)% v 43(4)%, P < 0.05], left ventricular pressure [81(8)% v 42(5)%, P < 0.05], phosphocreatine [105(4)% v 67(8)%, P < 0.05], and beta-ATP [78(9)% v 48(7)%, P < 0.05]. With BK-post, recovery of coronary flow [71(4)% v 43(4)%, P < 0.05] and left ventricular pressure [78(4)% v 42(5)%, P < 0.05] significantly improved; however the recovery of phosphocreatine [70(4)% v 67(8)%, NS] and beta-ATP [58(2)% v 48(7)%, NS] was not different from control. When bradykinin and L-NAME or indomethacin was given the beneficial effects of bradykinin on ischaemic hearts were abolished. CONCLUSIONS: (1) Bradykinin improved postischaemic myocardial recovery when given before ischaemia or starting exclusively with reperfusion; (2) this was only partially related to a protective action on the high energy phosphate compounds during ischaemia; (3) the beneficial effects of bradykinin on ischaemic hearts are dependent from an unrestrained action of prostacyclin and nitric oxide.

Intracellular calcium transients underlying interval-force relationship in whole rat hearts: effects of calcium antagonists.

OBJECTIVES: Much of the understanding about the cardiac interval-force relationship of the whole heart, including mechanical restitution and postextrasystolic potentiation (PESP), has been inferred from isolated muscle studies. We tested whether results from isolated muscles about intracellular Ca2+([Ca2+]i) transients underlying the interval-force relationship can be substantiated in whole hearts. Additionally, we investigated whether Ca2+ antagonists could alter [Ca2+]i transients underlying mechanical restitution and postextrasystolic potentiation. METHODS: [Ca2+]i transients were studied in isolated perfused rat hearts by surface fluorometry and Indo-1. Using computer-controlled pacing protocols, we performed restitution curves for left ventricular developed pressure and [Ca2+]i (developed pressure and [Ca2+]i plotted as a function of extrasystolic intervals). To quantify restitution curves, we fitted monoexponential functions to plots and analyzed their shift and slope. Then, we used Ca2+ antagonists, low extracellular Ca2+([Ca2+]o) and PESP to modify restitution curves. [Ca2+]i transients in isolated rat hearts were interpreted as Ca2+ released from the sarcoplasmic reticulum. RESULTS: Interval-dependent changes in developed pressure were strongly correlated to interval-dependent changes in the amplitude of [Ca2+]i transients in isolated whole rat hearts. Additionally, nifedipine and low [Ca2+]o led to similar downward shifts but not to a changed slope of restitution curves for [Ca2+]i. On the other hand, PESP increased the slope of restitution curves for [Ca2+]i. Furthermore, the effect of PESP on developed pressure was blunted by high concentrations of Ca2+ antagonists. CONCLUSIONS: The results from isolated muscles about [Ca2+]i transients underlying the interval-force relationship could be substantiated in whole hearts. Additionally, low [Ca2+]i (induced by nifedipine or low [Ca2+]o) decreased the maximal Ca2+ release of the sarcoplasmic reticulum but did not change the release kinetics. On the other hand, PESP presumably accelerated Ca2+ release kinetics of the sarcoplasmic reticulum.

Oral anticoagulation in the prevention of one-year vein graft occlusion after aortocoronary bypass surgery: optimal therapeutic range and practical limitations. CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands.

To assess the optimal level of oral anticoagulation to prevent occlusion of vein coronary bypass grafts, 318 patients from a graft patency trial were analysed retrospectively. Oral anticoagulant therapy was started one day before surgery and continued for one year, after which graft occlusion was assessed by angiography. The aimed level of anticoagulation was 2.8-4.8 International Normalized Ratio (INR). Clinical outcome was assessed by the incidence of myocardial infarction, thrombosis and major bleeding. The observed anticoagulation level was 2.8-4.8 INR for 54%, and 1.8-3.8 INR for 75% of time per patient. Occlusion rates in patients who spent < 35, 35-70, and > or = 70% of time within INR range 2.8-4.8 were 10.5%, 10.8% and 11.8%, respectively (differences not statistically significant). Patients who spent > or = 70% of time within INR range 1.8-3.8 versus 2.8-4.8 showed comparable occlusion rates. The risk of graft occlusion was not related to quality of anticoagulation early (0-3 months) or late (3-12 months) after surgery. Myocardial infarction, thrombosis and major bleeding occurred in 1.3%, 2.0% and 2.9% of patients. To maintain vein graft patency in the first postoperative year by oral anticoagulation, a level within INR range 1.8-3.8 for > or = 70% of time seems to be sufficient.

Combined blockade of endothelin-1 and thromboxane A(2) receptors against postischaemic contractile dysfunction in rat hearts.

1. Endothelin-1 (ET-1) may play a role in myocardial ischaemia/reperfusion injury because both the release and vasoconstrictor effect of ET-1 are increased after ischaemia. Since the increased vasoconstrictor effect of ET-1 can be mediated by ET-1-induced release of thromboxane A(2) (TXA(2)), the aim of this study was to test whether combined blockade of ET and TXA(2) receptors protects the coronary flow, contractile performance, and cardiac energy metabolism during ischaemia and reperfusion. 2. Bosentan (antagonist for ET(A) and ET(B) receptors, 1 microM based on concentration-response curves of ET-1), SQ 30,741 (antagonist of TXA(2) receptors, 0.1 microM), or the combination thereof was administered to isolated perfused rat hearts undergoing 15 min of global ischaemia and 60 min of reperfusion. 3. Neither bosentan or SQ 30,741 alone, nor the combination thereof, improved the incomplete postischaemic recovery of coronary flow, left ventricular developed pressure, phosphocreatine, or ATP. However, they attenuated ischaemia-induced acidosis but this did not translate into a measurable effect on haemodynamic or metabolic variables. 4. Thus, combined blockade of ET and TXA(2) receptors does not protect the coronary flow, contractile performance, and cardiac energy metabolism during ischaemia and reperfusion in isolated perfused rat hearts. This finding suggests that neither ET-1 nor ET-1-induced release of TXA(2) play a major role in the postischaemic recovery of the cardiac contractile function and energy metabolism.

Placement of a temporary pacemaker electrode through a persistent left superior vena cava.

Perioperative temporary pacing was needed in a patient with congenital skeletal malformations and a cardiac conduction disturbance with incomplete trifascicular block. We report the successful placement of the pacemaker electrode through a persistent left superior vena cava (SVC).

Prevention of supraventricular tachyarrhythmias after open heart operation by low-dose sotalol: a prospective, double-blind, randomized, placebo-controlled study.

BACKGROUND: The aim of this prospective, double-blind, placebo-controlled trial was to assess the preventive effect and safety of low-dose sotalol after heart operation. METHODS: Two hundred fifty-five consecutive patients referred for elective coronary artery bypass grafting (n = 220) or aortic valve operation (n = 35) were randomized to receive either 80 mg of sotalol twice daily (n = 126) or matching placebo (n = 129) for 3 months, with the first dose given 2 hours before operation. RESULTS: There were no significant baseline differences between the groups. Overall, supraventricular tachyarrhythmias occurred in 36% of patients (82% atrial fibrillation). Hospital stay was 11.6 +/- 5 days in patients with supraventricular arrhythmias, versus 9.5 +/- 2.4 days in patients without it (p < 0.0001). Low-dose sotalol reduced the rate of supraventricular arrhythmias from 46% (placebo) to 26% (sotalol; p = 0.0012), or by 43%. On the fourth postoperative day, heart rate was lower in the sotalol group (74 +/- 12 beats/min versus 85 +/- 15 beats/min; p < 0.0001) but the QT interval corrected for the heart rate was not prolonged (sotalol group, 0.44 +/- 0.03 second; placebo group, 0.43 +/- 0.03 second; p = not significant). Study medication had to be discontinued because of side effects in 5.6% of sotalol and 3.9% of placebo patients (p = not significant), with one possible proarrhythmic event occurring in a patient receiving sotalol. CONCLUSIONS: Because more than 90% of supraventricular arrhythmic episodes occurred within 9 days after operation and 70% of all possibly sotalol related side effects occurred after day 9, the findings in this study imply that prophylactic treatment with sotalol may be limited to the first 9 postoperative days.

Regional wall motion assessment in stress echocardiography by tissue Doppler bull's-eyes.

Quantification of regional myocardial wall velocities is needed in stress echocardiography for transition from subjective to quantitative assessment. Tissue Doppler allows quantitation of wall velocities, but interpretation is difficult and angle-dependent. Calculating the ratios of velocities with similar angles to the beam may overcome angle dependency. We measured left ventricular wall velocities during stress echocardiography with tissue Doppler. Regional peak systolic and early (E) and late (A) diastolic velocities were constructed in a "bull's-eye" format. Regional stress/rest and E/A ratios were calculated. Bull's-eye map construction demanded only minimal manual interaction, and the maps showed the left ventricular velocity distribution, simplifying wall motion reading markedly. Still, apical velocities appeared lower as a result of Doppler angle-dependency. With velocity ratios, angle-dependency was no longer noted. In stress echocardiography, wall motion abnormalities at rest and contractility changes with dobutamine became readily apparent. Bull's-eye display of quantitative tissue Doppler velocity allows rapid assessment of regional wall motion. Calculating the ratio of regional velocities circumvents the angle-dependency of Doppler. This novel technique has the potential for simplified and automated quantitative analysis in stress echocardiography.

Long-term outcome of angioplasty for multivessel coronary disease: importance and price of complete revascularization.

BACKGROUND: Complete revascularization of multivessel coronary artery disease (MVD) by coronary artery bypass surgery has been shown to improve outcome, but there is a lack of similar data for patients treated by angioplasty. METHODS: Therefore, a consecutive series of 250 patients with MVD was separated into two groups, those with complete revascularization (n=101) and those with incomplete revascularization (n=149). Six-month 'clinical restenosis' rate assessed by stress myocardial perfusion scintigraphy or symptom-driven angiography and long-term 32 months outcome were compared with an equally sized group of single vessel disease (SVD) patients. RESULTS: MVD patients with complete revascularization had a higher 'clinical restenosis' rate than patients with SVD (35 vs. 22%, P<0.02), although restenosis rate per treated vessel was similar (23%, 18%, P NS). If this higher early restenosis rate were accepted as 'price' for complete MVD angioplasty, long-term event-free survival was no longer different from that of SVD patients (86 vs. 93%, P NS). In contrast, patients with incomplete multivessel angioplasty had a significantly worse long-term outcome (22% events), especially if initially untreated, non-occluded vessels remained untreated (25% events). CONCLUSION: MVD angioplasty with complete revascularization has a long-term event-free survival similar to that of SVD angioplasty but at the price of a higher rate of 6-month restenosis and repeat interventions.

Accuracy of biplane analysis of left ventricular ejection fraction based on two consecutive single plane studies.

BACKGROUND AND PURPOSE: Mainly due to the high costs of biplane equipment many cardiac laboratories run single plane angiographic equipment only. Consequently, a biplane ventriculogram may only be done with two consecutive single plane studies. The aim of this investigation was to assess the accuracy of a biplane analysis of two consecutive single plane studies. METHODS: A total of 42 patients (62 +/- 10 years, 76% males), able to tolerate two consecutive ventriculograms without arrhythmia during the first study underwent two consecutive biplane studies (LAO 60, RA0 30), using 40 ml of contrast each. After the first injection, the x-ray tube was moved in a neutral position, and then was replaced in the 30 RAO/60 LAO position. Digital data was analyzed by two separate investigators using commercially available software. RESULTS: Intra-observer variability of left ventricular ejection fraction (LVEF) showed a high degree of agreement (single plane 1 vs. 2: r = 0.98; standard error of regression (Sy.x.): 2.8); the variability was slightly higher with two investigators (single plane: r = 0.92, Sy.x: 5.5 ) and with biplane analysis (biplane 1 vs. 2: r = 0.90, Sy. x: 5.7). End-diastolic volume index (EDVI) increased significantly from the first to the second study (84 +/- 28 ml/m2 vs 87 +/- 30 ml/m2; p = 0.017): Still LVEF of the two consecutive biplane studies showed very good agreement (biplane 1 vs. 2: mean difference (MD), -1.0; standard deviation of the difference (SDD), 5.2%). This agreement was almost as good as the one of LVEF values calculated from two consecutive single plane, but biplane analyzed studies compared to simultaneous biplane studies (MD, -0.5; SDD, 4.3%). CONCLUSION: Despite the significant increase in EDVI after contrast injection, LVEF values determined from two consecutive studies remained virtually unchanged. Biplane analysis of LVEF values based on consecutive single plane studies resulted in similar and reliable values as determined by two consecutive biplane studies.

Effects of morphologic restenosis, defined by MRI after coarctation repair, on blood pressure and arm-leg and Doppler gradients.

Ten years after coarctation repair, 36 adolescents and young adults were studied in order to evaluate the relationship of anatomy at the resection site to blood pressure and arm-leg and Doppler gradients. The patients underwent magnetic resonance imaging (MRI), exercise testing, and continuous wave (CW) Doppler echocardiography. On MRI, residual narrowing at the resection site was measured as 1-(phi anastomosis/ phi descending aorta) and expressed as percent stenosis. Residual stenosis on MRI was negatively correlated with the leg pressure at rest (P = 0.0003) and during exercise (P = 0.002). Residual stenosis correlated positively with the arm-leg gradient at rest (P < 0.0001) and during exercise (P < 0.0001) and with the peak CW Doppler gradient across the anastomosis (P < 0.0001). However, residual stenosis was not related to the systolic blood pressure of the arm at rest or during exercise. The systolic arm pressures did not differ between patients with residual stenosis of less than 30% (group I), patients with residual stenosis of equal to or greater than 30% but less than 45% (group II), and patients with residual stenosis of equal to or greater than 45% (group III). In conclusion residual anatomic stenosis influences blood pressure in the legs, the arm-leg gradient, and the Doppler gradient across the anastomosis. Arm hypertension late after coarctation repair seems not to be related to residual stenosis, and the benefit of reintervention in these patients remains questionable.

[Magnetic resonance imaging: cardiological diagnosis]. / Magnet Resonanz Imaging: kardiologische Diagnostik.

Cardiovascular magnetic resonance imaging (MRI) has been in clinical use for barely a decade. During this relatively short period MRI has established itself as an important diagnostic instrument. MRI is an intrinsically three-dimensional, completely noninvasive technique. Its inherent high contrast between the flowing blood on the surrounding tissue make MRI an ideal diagnostic method for cardiovascular diseases, since it does not expose patients and staff to ionizing radiation and there is no need for the application of contrast media. The high spatial and excellent contrast resolution are the basis for the distinct delineation of the cardiovascular pathoanatomy. Infarcted and non-infarcted myocardium may be differentiated by the assessment of tissue relaxation times. With the use of Cine MRI, global and regional ventricular function may be quantified and bloodflow within cardiac chambers may be analyzed. Today's indications for cardiovascular MRI based on personal experience and the literature are presented.

[Transesophageal echocardiography: technique, indications and findings]. / Transösophageale Echokardiographie: Technik, Indikationen und Befunde.

The introduction of transesophageal echocardiography (TEE) as a 'semi-invasive' technique with few complications in clinical practice represents a major diagnostic advance in the evaluation of cardiac disease. The close anatomic vicinity of the transducer to the heart and thoracic aorta allows the use of high frequency devices with better resolution compared to transthoracic echocardiography. Furthermore, the diagnostic gain when evaluating structures that are poorly visualized by the transthoracic approach such as the left atrial appendage, interatrial septum, prosthetic valves and the thoracic aorta is highly improved by TEE. Major indications for TEE include the search for a cardiac source of embolism and cardiac tumors, the work-up prior to balloon mitral valvuloplasty, the evaluation of prosthetic valves and the search for vegetations and aortic dissection. After a short summary of patient preparation, instrumentation and examination technique, the major indications, contraindications and complications are reviewed on the basis of our own experience and the literature.

Improvements in physical and mental domains of quality of life by anti-ischaemic drug and revascularisation treatment in elderly men and women with chronic angina.

BACKGROUND: The severity of angina is related to a reduction in global quality of life (QoL), which may be improved by anti-ischaemic treatment. It is not known, however, whether improvements relate only to physical or also to mental and social domains of QoL and whether women benefit in a similar way to men. OBJECTIVES: To relate improvements in angina severity through anti-ischaemic treatment to physical and mental domains of QoL in elderly men and women and to assess differences in this relation between the sexes. METHODS: Angina severity and full assessment of QoL by structured, self-administered and validated questionnaires were measured prospectively at baseline and after 6 months' optimal drug or revascularisation treatment in all 301 patients of the Trial of Invasive versus Medical therapy in Elderly (TIME) patients with chronic angina. RESULTS: At baseline, angina severity correlated significantly with physical domains of QoL (trend test at least p<0.02) and daily activities (p = 0.05). At similar angina levels, women had significantly lower QoL scores than men. With anti-ischaemic treatment, physical as well as mental and social QoL domains and daily activities improved, together with a relief in angina (trend tests at least p<0.02). This was true for women and men and was more pronounced after revascularisation than with medical treatment. CONCLUSIONS: These findings confirm the relation between angina severity and physical limitation. In addition, they show that anti-ischaemic treatment not only relieves angina and improves physical components of QoL but also improves mental and social domains. This is true for women as well as for men despite the lower overall scores for women.

The future of cardiovascular imaging and non-invasive diagnosis: a joint statement from the European Association of Echocardiography, the Working Groups on Cardiovascular Magnetic Resonance, Computers in Cardiology, and Nuclear Cardiology, of the European Society of Cardiology, the European Association of Nuclear Medicine, and the Association for European Paediatric Cardiology.

Advances in medical imaging now make it possible to investigate any patient with cardiovascular disease using multiple methods which vary widely in their technical requirements, benefits, limitations, and costs. The appropriate use of alternative tests requires their integration into joint clinical diagnostic services where experts in all methods collaborate. This statement summarises the principles that should guide developments in cardiovascular diagnostic services.

[Stress echocardiography versus scintigraphy in evaluating coronary heart disease: stress echocardiography is superior]. / Stress-Echokardiographie versus Szintigraphie zur Beurteilung der koronaren Herzkrankheit: die Stress-Echokardiographie is überlegen.

Stress echocardiography has evolved as a routinely employed non-invasive method for the evaluation of patients with coronary artery disease. The diagnostic accuracy of stress echocardiography for the detection of myocardial ischemia is comparable to scintigraphic myocardial perfusion imaging, and may even have a higher specificity for the evaluation of myocardial viability. User-friendliness including patient and investigator safety, availability and mobility of the method, and environmental compatibility, is superior to that of scintigraphy. The potential for future developments, especially in the field of digital imaging and telecommunication, is great. Last but not least, echocardiography is the method most familiar to cardiologists. The sum of these arguments renders stress echocardiography the superior method to scintigraphy in the evaluation of patients with coronary artery disease.

When calcium turns arrhythmogenic: intracellular calcium handling during the development of hypertrophy and heart failure.

Alterations of intracellular Ca2+ handling in hypertrophied myocardium have been proposed as a mechanism of ventricular tachyarrhythmias, which are a major cause of sudden death in patients with heart failure. In this review, alterations in intracellular Ca2+ handling and Ca2+ handling proteins in the development of myocardial hypertrophy and the transition to heart failure are discussed. The leading question is at what stage of hypertrophy or heart failure Ca2+ handling can turn arrhythmogenic. During the development of myocardial hypertrophy and the transition to failure, Ca2+ handling is progressively altered. Recordings of free myocyte Ca2+ concentrations during a cardiac cycle (Ca2+ transients) are prolonged early in the development of hypertrophy. However, resting (or diastolic) Ca2+ does not increase before end-stage heart failure has developed. These alterations are due to progressively defective Ca2+ uptake into the sarcoplasmic reticulum that seems to be caused by quantitative changes of gene expression of the Ca2+ ATPase of the sarcoplasmic reticulum. Increased expression and activity of the Na+/Ca2+ exchanger might compensate for this defective Ca2+ uptake, probably at the expense of increased arrhythmogenicity. When the Ca2+ handling proteins no longer efficiently counterbalance increasing intracellular Ca2+ - during stress conditions, resulting Ca2+ overload can lead to spontaneous intracellular Ca2+ oscillations, after depolarizations. Thus, after the transition to heart failure, Ca2+ overloaded sarcoplasmic reticulum, increasing resting intracellular Ca2+, and increased Na+/Ca2+ activity may all provoke afterdepolarizations, triggered activity, and finally, life-threatening ventricular arrhythmias. This increased susceptibility to ventricular arrhythmias in heart failure should not be treated with calcium antagonists.