Hans A. Bosker

Lenient versus Strict Rate Control in Patients with Atrial Fibrillation

BACKGROUNDnRate control is often the therapy of choice for atrial fibrillation. Guidelines recommend strict rate control, but this is not based on clinical evidence. We hypothesized that lenient rate control is not inferior to strict rate control for preventing cardiovascular morbidity and mortality in patients with permanent atrial fibrillation.nnnMETHODSnWe randomly assigned 614 patients with permanent atrial fibrillation to undergo a lenient rate-control strategy (resting heart rate <110 beats per minute) or a strict rate-control strategy (resting heart rate <80 beats per minute and heart rate during moderate exercise <110 beats per minute). The primary outcome was a composite of death from cardiovascular causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events. The duration of follow-up was at least 2 years, with a maximum of 3 years.nnnRESULTSnThe estimated cumulative incidence of the primary outcome at 3 years was 12.9% in the lenient-control group and 14.9% in the strict-control group, with an absolute difference with respect to the lenient-control group of -2.0 percentage points (90% confidence interval, -7.6 to 3.5; P<0.001 for the prespecified noninferiority margin). The frequencies of the components of the primary outcome were similar in the two groups. More patients in the lenient-control group met the heart-rate target or targets (304 [97.7%], vs. 203 [67.0%] in the strict-control group; P<0.001) with fewer total visits (75 [median, 0], vs. 684 [median, 2]; P<0.001). The frequencies of symptoms and adverse events were similar in the two groups.nnnCONCLUSIONSnIn patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve. (ClinicalTrials.gov number, NCT00392613.)

Familial evaluation in catecholaminergic polymorphic ventricular tachycardia disease penetrance and expression in cardiac ryanodine receptor mutation-carrying relatives

Background— Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene ( Ryr2 ) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease penetrance, expression, genotype-phenotype correlations, and arrhythmic event rates in relatives carrying the Ryr2 mutation is limited.nnMethods and Results— One-hundred sixteen relatives carrying the Ryr2 mutation from 15 families who were identified by cascade screening of the Ryr2 mutation causing CPVT in the proband were clinically characterized, including 61 relatives from 1 family. Fifty-four of 108 antiarrhythmic drug-free relatives (50%) had a CPVT phenotype at the first cardiological examination, including 27 (25%) with nonsustained ventricular tachycardia. Relatives carrying a Ryr2 mutation in the C-terminal channel-forming domain showed an increased odds of nonsustained ventricular tachycardia (odds ratio, 4.1; 95% CI, 1.5–11.5; P =0.007, compared with N-terminal domain) compared with N-terminal domain. Sinus bradycardia was observed in 19% of relatives, whereas other supraventricular dysrhythmias were present in 16%. Ninety-eight (most actively treated) relatives (84%) were followed up for a median of 4.7 years (range, 0.3–19.0 years). During follow-up, 2 asymptomatic relatives experienced exercise-induced syncope. One relative was not being treated, whereas the other was noncompliant. None of the 116 relatives died of CPVT during a 6.7-year follow-up (range, 1.4–20.9 years).nnConclusions— Relatives carrying an Ryr2 mutation show a marked phenotypic diversity. The vast majority do not have signs of supraventricular disease manifestations. Mutation location may be associated with severity of the phenotype. The arrhythmic event rate during follow-up was low.Background— Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (Ryr2) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease penetrance, expression, genotype-phenotype correlations, and arrhythmic event rates in relatives carrying the Ryr2 mutation is limited. Methods and Results— One-hundred sixteen relatives carrying the Ryr2 mutation from 15 families who were identified by cascade screening of the Ryr2 mutation causing CPVT in the proband were clinically characterized, including 61 relatives from 1 family. Fifty-four of 108 antiarrhythmic drug-free relatives (50%) had a CPVT phenotype at the first cardiological examination, including 27 (25%) with nonsustained ventricular tachycardia. Relatives carrying a Ryr2 mutation in the C-terminal channel-forming domain showed an increased odds of nonsustained ventricular tachycardia (odds ratio, 4.1; 95% CI, 1.5–11.5; P=0.007, compared with N-terminal domain) compared with N-terminal domain. Sinus bradycardia was observed in 19% of relatives, whereas other supraventricular dysrhythmias were present in 16%. Ninety-eight (most actively treated) relatives (84%) were followed up for a median of 4.7 years (range, 0.3–19.0 years). During follow-up, 2 asymptomatic relatives experienced exercise-induced syncope. One relative was not being treated, whereas the other was noncompliant. None of the 116 relatives died of CPVT during a 6.7-year follow-up (range, 1.4–20.9 years). Conclusions— Relatives carrying an Ryr2 mutation show a marked phenotypic diversity. The vast majority do not have signs of supraventricular disease manifestations. Mutation location may be associated with severity of the phenotype. The arrhythmic event rate during follow-up was low.

Continuous vs episodic prophylactic treatment with amiodarone for the prevention of atrial fibrillation : a randomized trial

CONTEXTnAmiodarone effectively suppresses atrial fibrillation but causes many adverse events.nnnOBJECTIVEnTo compare major events in patients randomized to receive episodic amiodarone treatment with those who received continuous amiodarone treatment while still aiming to prevent atrial fibrillation.nnnDESIGN, SETTING, AND PARTICIPANTSnA randomized trial of 209 ambulatory patients with recurrent symptomatic persistent atrial fibrillation, conducted from December 2002 through March 2007 at 7 Dutch medical centers.nnnINTERVENTIONnPatients were randomly assigned to receive either episodic or continuous amiodarone treatment after electrical cardioversion following amiodarone loading. Episodic amiodarone treatment was discontinued after a month of sinus rhythm and reinitiated if atrial fibrillation relapsed (1 month peri-electrical cardioversion). In the continuous treatment group amiodarone was maintained throughout.nnnMAIN OUTCOME MEASURESnThe primary end point was a composite of amiodarone and underlying heart disease-related major events. The secondary end points were all-cause mortality and cardiovascular hospitalizations.nnnRESULTSnAfter a median follow-up of 2.1 years (range, 0.4-2.5 years), 51 (48%) of those receiving episodic treatment vs 64 (62%) receiving continuous treatment had sinus rhythm (P = .05). There were 85 atrial fibrillation recurrences (80%) among the episodic treatment group vs 56 (54%) in the continuous treatment group (P < .001). No significant difference existed in the incidence of the primary composite end point between each group (37 [35%] episodic vs 34 [33%] continuous; incidence rate difference, 0.2; 95% confidence interval [CI], -10.2 to 10.6). However, there were nonstatistically significant differences in the incidence of amiodarone-related major events (20 [19%] episodic vs 25 [24%] continuous; incidence rate difference, -2.0; 95% CI, -8.7 to 4.6) and underlying heart disease-related major events (17 [16%] episodic vs 9 [9%] continuous; incidence rate difference, 3.6; 95% CI, -1.6 to 8.7). All-cause mortality and cardiovascular hospitalizations were higher among those receiving episodic treatment (56 [53%] vs 35 [34%], P = .02).nnnCONCLUSIONSnIn this study population, there was no difference in the composite of amiodarone and cardiac major adverse events between groups. However, patients receiving episodic treatment had a significantly increased rate of atrial fibrillation recurrence and a significantly higher rate of all-cause mortality and cardiovascular hospitalizations.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00392431.

Incidence, risk factors, and predictors of infective endocarditis in adult congenital heart disease: focus on the use of prosthetic material

AimsnAdult congenital heart disease (ACHD) predisposes to infective endocarditis (IE). Surgical advancements have changed the ACHD population, whereas associated prosthetic material may constitute additional IE targets. We aimed to prospectively determine contemporary incidence, risk factors, and predictors of IE in a nationwide ACHD cohort, focusing on the presence of prosthetics.nnnMethods and resultsnWe identified 14xa0224 patients prospectively followed in the CONCOR ACHD registry (50.5% female, median age 33.6years). IE incidence was determined using Poisson regression, risk factors and predictors using Cox regression. Overall incidence was 1.33 cases/1000 person-years (124 cases in 93xa0562 person-years). For risk-factor analysis, presence of prosthetics was forced-as separate time-updated variables for specific prosthetics-into a model with baseline characteristics univariably associated with IE. Valve-containing prosthetics were independently associated with greater risk both short- and long term after implantation [0-6 months: hazard ratio (HR)u2009=u200917.29; 7.34-40.70, 6-12 months: HRu2009=u200915.91; 6.76-37.45, beyond 12 months: HRu2009=u20095.26; 3.52-7.86], non-valve-containing prosthetics, including valve repair, only in the first 6 months after implantation (HRu2009=u20093.34; 1.33-8.41), not thereafter. A prediction model was derived and validated using bootstrapping techniques. Independent predictors of IE were baseline valve-containing prosthetics, main congenital heart defect, multiple defects, previous IE, and sex. The model had fair discriminative ability and provided accurate predictions up to 10 years.nnnConclusionsnThis study provides IE incidence estimates, and determinants of IE risk in a nationwide ACHD cohort. Our findings, essentially informing IE prevention guidelines, indicate valve-containing prosthetics as a main determinant of IE risk whereas other prosthetics, including valve-repair, are not associated with increased risk long term after implantation.

Serum-Sickness-Like Illness as a Complication after Streptokinase Therapy for Acute Myocardial Infarction

We report a case of serum-sickness-like illness in a 47-year-old patient who received early high-dose intravenous and intracoronary streptokinase following acute myocardial infarction. The picture comprised severe arthralgias, fever, an urticarial rash and marked elevation of circulating immune complexes. This case represents a rare complication of streptokinase therapy.

Acute myocardial infarction with cardiogenic shock in a patient with acute aortic dissection

Diagnosing acute Stanford type A aortic dissection with the uncommon involvement of the left main coronary artery(LMCA) remains challenging for the emergency physician because it can resemble acute myocardial infarction with cardiogenic shock. The following case report illustrate this infrequent but critical situation. A 52-year-old woman with a history of hypertension awakened with acute retrosternal chest pain accompanied by nausea and vomiting. She was referred to our hospital for primary coronary intervention because of acute myocardial infarction with cardiogenic shock. Coronary angiography indeed revealed LMCA occlusion. Subsequently successful percutaneous coronary intervention with stent implantation was performed, followed by immediate clinical improvement of the patient. Soon after admission at the coronary care unit, severe chest pain, hypotension, and electrocardiographic signs of diffuse myocardial ischemia relapsed. Control coronary angiography,however, showed no in-stent thrombosis. Review of clinical examination revealed an aortic regurgitation murmur. Because of this dynamic pattern of (1) signs of acute myocardial ischemia, (2) relapse of hemodynamic collapse, and (3) unaltered control coronary angiography together with the confirmed aortic regurgitation at transthoracic echocardiography, the patient was suspected of having aortic dissection. Transesophageal echocardiography revealed Stanford type A aortic dissection with severe eccentric aortic regurgitation and no pericardial effusion. Emergent valve-sparing aortic replacement was performed. The patient recovered completely. In this case, the lifesaving element was primary coronary intervention with stenting of the LMCA preventing extensive myocardial damage followed by a surgical correction of the aorta.

The effects of diltiazem on cardiac function in silent ischemia after myocardial infarction

In a total group of 56 patients with an acute myocardial infarction who were maximally exercised at predischarge, 20 patients (36%) showed greater than or equal to 1 mm asymptomatic ST-T segment depression during exercise. The site of the infarction was anterior in 12 patients and inferior in eight patients. All 20 patients underwent repeated exercise radionuclide angiography 2 days later, 2 hours following oral intake of 120 mg of diltiazem. Double product was not significantly different before and after diltiazem, both at rest and during exercise. Maximal ST-T depression after diltiazem was reduced from 2.3 +/- 0.8 to 0.7 +/- 0.6 mm (p less than 0.01). Left ventricular (LV) ejection fraction at rest before diltiazem was 54.4 +/- 8.7% and after diltiazem was 56.2 +/- 11.3% (p = NS). During exercise, LV ejection fraction improved after diltiazem from 43.2 +/- 12.2% to 49.8 +/- 10.5% (p less than 0.05). Regional wall motion score (1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic) at rest before diltiazem was 9.6 +/- 2.0 and after diltiazem was 9.1 +/- 1.8 (p = NS). During exercise, regional wall motion score improved after diltiazem from 5.8 +/- 1.3 to 4.3 +/- 1.1 (p less than 0.02). We conclude that silent ischemia occurs in a substantial number of patients after myocardial infarction and that diltiazem has acute beneficial effects on asymptomatic ST-T depression and on global and regional LV function in post-infarction patients with silent ischemia.

Are enzymatic tests good indicators of coronary reperfusion

OBJECTIVE--To assess the accuracy of four enzymatic tests, including early release rates of creatine kinase and alpha-hydroxybutyrate dehydrogenase, in assessing coronary reperfusion after thrombolytic therapy. DESIGN--A prospective clinical trial identifying patients with a successful thrombolytic treatment. PATIENTS--Eighty nine patients with acute myocardial infarction were studied. Arteriography showed a closed infarct related artery in all of them. Reperfusion due to thrombolysis occurred in 74 patients and there was no reperfusion in 15 patients. RESULTS--The 74 patients showing coronary reperfusion had a significantly shorter time to peak creatine kinase activity, higher early release rates for creatine kinase and alpha-hydroxybutyrate dehydrogenase, and a more rapid release of alpha-hydroxybutyrate dehydrogenase (ratio of cumulative release of alpha-hydroxybutyrate dehydrogenase during the first 24 hours to that 72 hours after infarction). All these differences were statistically significant (p less than 0.001). Optimum cut off levels were determined with decision level plots and the accuracy of the four enzymatic tests was calculated. Accuracy was low for all four tests (73%, 70%, 70%, and 82%). CONCLUSION--None of the four enzymatic tests accurately predicted the perfusion state of the infarct related coronary artery after thrombolysis. These tests cannot be used reliably in routine clinical practice as non-angiographic markers of coronary reperfusion.

Coronary angiography after cardiac arrest: Rationale and design of the COACT trial

BACKGROUNDnIschemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography (CAG) and percutaneous coronary intervention (PCI) after restoration of spontaneous circulation following cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains debated.nnnHYPOTHESISnWe hypothesize that immediate CAG and PCI, if indicated, will improve 90-day survival in post-cardiac arrest patients without signs of STEMI.nnnDESIGNnIn a prospective, multicenter, randomized controlled clinical trial, 552 post-cardiac arrest patients with restoration of spontaneous circulation and without signs of STEMI will be randomized in a 1:1 fashion to immediate CAG and PCI (within 2 hours) versus initial deferral with CAG and PCI after neurological recovery. The primary end point of the study is 90-day survival. The secondary end points will include 90-day survival with good cerebral performance or minor/moderate disability, myocardial injury, duration of inotropic support, occurrence of acute kidney injury, need for renal replacement therapy, time to targeted temperature control, neurological status at intensive care unit discharge, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, and reasons for discontinuation of treatment.nnnSUMMARYnThe COACT trial is a multicenter, randomized, controlled clinical study that will evaluate the effect of an immediate invasive coronary strategy in post-cardiac arrest patients without STEMI on 90-day survival.

The time course of ECG-parameters has no quantitative significance in the thrombolytic era

Spatial ST-vector magnitudes, mod ST/sub 40-80/ mod , were measured every 3 min for at least 3 h after admission, and at wider intervals for 3 days. Likewise, the magnitudes of the difference vector mod Delta QRS mod between the vectorcardiogram (VCG) on admission and a subsequent VCG were determined. The VCG was synthesized from eight electrocardiogram (ECG) leads through linear transformation. The study included 18 patients, only three of whom did not undergo interventions. mod ST/sub 40-80/ mod was always maximal on admission and declined to a stable level in about 4.5. Over the same time span mod Delta QRS mod showed an inconspicuous rise. Correlation of these parameters with infarct size determined by 76 h cumulative serum a-hydroxy-butyrate dehydrogenase activity was poor. Evidently, important ECG charges have already taken place before admission, but even allowing for this, little quantitative relation between VCG parameters and infarct size was apparent.<<ETX>>