Peter Ong

Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy.

OBJECTIVES We sought to establish the prognostic value of a comprehensive cardiovascular magnetic resonance (CMR) examination in risk stratification of hypertrophic cardiomyopathy (HCM) patients. BACKGROUND With annual mortality rates ranging between 1% and 5%, depending on patient selection, a small but significant number of HCM patients are at risk for an adverse event. Therefore, the identification of and prophylactic therapy (i.e., defibrillator placement) in patients with HCM who are at risk of dying are imperative. METHODS Two-hundred forty-three consecutive patients with HCM were prospectively enrolled. All patients underwent initial CMR, and 220 were available for clinical follow-up. The mean follow-up time was 1,090 days after CMR. End points were all-cause and cardiac mortality. RESULTS During follow-up 20 of the 220 patients died, and 2 patients survived sudden cardiac death due to adequate implantable cardioverter-defibrillator discharge. Most events (n = 16) occurred for cardiac reasons; the remaining 6 events were related to cancer and accidents. Our data indicate that the presence of scar visualized by CMR yields an odds ratio of 5.47 for all-cause mortality and of 8.01 for cardiac mortality. This might be superior to classic clinical risk factors, because in our dataset the presence of 2 risk factors yields an odds ratio of 3.86 for all-cause and of 2.20 for cardiac mortality, respectively. Multivariable analysis also revealed the presence of late gadolinium enhancement as a good independent predictor of death in HCM patients. CONCLUSIONS Among our population of largely low or asymptomatic HCM patients, the presence of scar indicated by CMR is a good independent predictor of all-cause and cardiac mortality.

Coronary artery spasm as a frequent cause of acute coronary syndrome: The CASPAR (Coronary Artery Spasm in Patients With Acute Coronary Syndrome) Study.

OBJECTIVES This study was conducted to clarify the incidence of coronary spasm in emergency patients with suspected acute coronary syndrome (ACS) and acute chest pain at rest. BACKGROUND Chest pain at rest is a frequent symptom in the emergency room. Acute coronary syndrome is suspected in patients with elevation of cardiac markers, ischemic electrocardiographic changes, or simply typical clinical symptoms of unstable (usually resting) angina. However, of all patients with suspected ACS who undergo coronary angiography, up to 30% have nonobstructed coronary arteries. We sought to clarify how many of these patients suffer from coronary spasm as a possible cause of their chest pain. METHODS In a prospective study from June to December 2006, all patients with suspected ACS who underwent coronary angiography and had no culprit lesion underwent intracoronary provocation with acetylcholine. The ACH testing was considered positive at a vasoconstriction of >/=75% relative to the diameter after intracoronary nitroglycerine when the initially reported symptoms could be reproduced. RESULTS Of 488 consecutive patients, 138 had no culprit lesion (28%). Twenty-two were found to have another diagnosis. The ACH testing was performed in 86 of the remaining 116 patients. In 42 patients, coronary spasm was verified (49%). CONCLUSIONS Every fourth patient with ACS had no culprit lesion. Coronary spasm could be documented in nearly 50% of the patients tested by ACH. Coronary spasm is a frequent cause of ACS and should regularly be considered as a differential diagnosis.

Long-Term Follow-Up of Biopsy-Proven Viral Myocarditis Predictors of Mortality and Incomplete Recovery

OBJECTIVES This study sought to evaluate the long-term mortality in patients with viral myocarditis, and to establish the prognostic value of various clinical, functional, and cardiovascular magnetic resonance (CMR) parameters. BACKGROUND Long-term mortality of viral myocarditis, as well as potential risk factors for poor clinical outcome, are widely unknown. METHODS A total of 222 consecutive patients with biopsy-proven viral myocarditis and CMR were enrolled. A total of 203 patients were available for clinical follow-up, and 77 patients underwent additional follow-up CMR. The median follow-up was 4.7 years. Primary endpoints were all-cause mortality and cardiac mortality. RESULTS We found a relevant long-term mortality in myocarditis patients (19.2% all cause, 15% cardiac, and 9.9% sudden cardiac death [SCD]). The presence of late gadolinium enhancement (LGE) yields a hazard ratio of 8.4 for all-cause mortality and 12.8 for cardiac mortality, independent of clinical symptoms. This is superior to parameters like left ventricular (LV) ejection fraction, LV end-diastolic volume, or New York Heart Association (NYHA) functional class, yielding hazard ratios between 1.0 and 3.2 for all-cause mortality and between 1.0 and 2.2 for cardiac mortality. No patient without LGE experienced SCD, even if the LV was enlarged and impaired. When focusing on the subgroup undergoing follow-up CMR, we found an initial NYHA functional class >I as the best independent predictor for incomplete recovery (p = 0.03). CONCLUSIONS Among our population with a wide range of clinical symptoms, biopsy-proven viral myocarditis is associated with a long-term mortality of up to 19.2% in 4.7 years. In addition, the presence of LGE is the best independent predictor of all-cause mortality and of cardiac mortality. Furthermore, initial presentation with heart failure may be a good predictor of incomplete long-term recovery.

CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis.

OBJECTIVES This study aimed to demonstrate that the presence of late gadolinium enhancement (LGE) is a predictor of death and other adverse events in patients with suspected cardiac sarcoidosis. BACKGROUND Cardiac sarcoidosis is the most important cause of patient mortality in systemic sarcoidosis, yielding a 5-year mortality rate between 25% and 66% despite immunosuppressive treatment. Other groups have shown that LGE may hold promise in predicting future adverse events in this patient group. METHODS We included 155 consecutive patients with systemic sarcoidosis who underwent cardiac magnetic resonance (CMR) for workup of suspected cardiac sarcoid involvement. The median follow-up time was 2.6 years. Primary endpoints were death, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator (ICD) discharge. Secondary endpoints were ventricular tachycardia (VT) and nonsustained VT. RESULTS LGE was present in 39 patients (25.5%). The presence of LGE yields a Cox hazard ratio (HR) of 31.6 for death, aborted sudden cardiac death, or appropriate ICD discharge, and of 33.9 for any event. This is superior to functional or clinical parameters such as left ventricular (LV) ejection fraction (EF), LV end-diastolic volume, or presentation as heart failure, yielding HRs between 0.99 (per % increase LVEF) and 1.004 (presentation as heart failure), and between 0.94 and 1.2 for potentially lethal or other adverse events, respectively. Except for 1 patient dying from pulmonary infection, no patient without LGE died or experienced any event during follow-up, even if the LV was enlarged and the LVEF severely impaired. CONCLUSIONS Among our population of sarcoid patients with nonspecific symptoms, the presence of myocardial scar indicated by LGE was the best independent predictor of potentially lethal events, as well as other adverse events, yielding a Cox HR of 31.6 and of 33.9, respectively. These data support the necessity for future large, longitudinal follow-up studies to definitely establish LGE as an independent predictor of cardiac death in sarcoidosis, as well as to evaluate the incremental prognostic value of additional parameters.

Detection of atrial high-rate events by continuous home monitoring: clinical significance in the heart failure-cardiac resynchronization therapy population.

Aims Uncertainty exists over the importance of device-detected short-duration atrial arrhythmias. Continuous atrial diagnostics, through home monitoring (HM) technology (BIOTRONIK, Berlin, Germany), provides a unique opportunity to assess frequency and quantity of atrial fibrillation (AF) episodes defined as atrial high-rate events (AHRE). Methods and results Prospective data from 560 heart failure (HF) patients (age 67 ± 10 years, median ejection fraction 27%) patients with a cardiac resynchronization therapy (CRT) device capable of HM from two multi-centre studies were analysed. Atrial high-rate events burden was defined as the duration of mode switch in a 24-h period with atrial rates of >180 beats for at least 1% or total of 14 min per day. The primary endpoint was incidence of a thromboembolic (TE) event. Secondary endpoints were cardiovascular death, hospitalization because of AF, or worsening HF. Over a median 370-day follow-up AHRE occurred in 40% of patients with 11 (2%) patients developing TE complications and mortality rate of 4.3% (24 deaths, 16 with cardiovascular aetiology). Compared with patients without detected AHRE, patients with detected AHRE>3.8 h over a day were nine times more likely to develop TE complications (P= 0.006). The majority of patients (73%) did not show a temporal association with the detected atrial episode and their adverse event, with a mean interval of 46.7 ± 71.9 days (range 0–194) before the TE complication. Conclusion In a high-risk cohort of HF patients, device-detected atrial arrhythmias are associated with an increased incidence of TE events. A cut-off point of 3.8 h over 24 h was associated with significant increase in the event rate. Routine assessment of AHRE should be considered with other data when assessing stroke risk and considering anti-coagulation initiation and should also prompt the optimization of cardioprotective HF therapy in CRT patients.

Clinical Usefulness, Angiographic Characteristics, and Safety Evaluation of Intracoronary Acetylcholine Provocation Testing Among 921 Consecutive White Patients With Unobstructed Coronary Arteries

Background— Coronary spasm can cause myocardial ischemia and angina in patients with and those without obstructive coronary artery disease. However, provocation tests using intracoronary acetylcholine administration are rarely performed in clinical routine in the United States and Europe. Thus, we assessed the clinical usefulness, angiographic characteristics, and safety of intracoronary acetylcholine provocation testing in white patients with unobstructed coronary arteries. Methods and Results— From September 2007 to June 2010, a total of 921 consecutive patients (362 men, mean age 62±12years) who underwent diagnostic angiography for suspected myocardial ischemia and were found to have unobstructed coronary arteries (no stenosis ≥50%) were enrolled. The intracoronary acetylcholine provocation testing was performed directly after angiography according to a standardized protocol. Three hundred forty-six patients (35%) reported chest pain at rest, 222 (22%) reported chest pain on exertion, 238 (24%) reported a combination of effort and resting chest pain, and 41 (4%) presented with troponin-positive acute coronary syndrome. The overall frequency of epicardial spasm (>75% diameter reduction with angina and ischemic ECG shifts) was 33.4%, and the overall frequency of microvascular spasm (angina and ischemic ECG shifts without epicardial spasm) was 24.2%. Epicardial spasm was most often diffuse and located in the distal coronary segments (P<0.01). No fatal or irreversible nonfatal complications occurred. However, 9 patients (1%) had minor complications (nonsustained ventricular tachycardia [n=1], fast paroxysmal atrial fibrillation [n=1], symptomatic bradycardia [n=6], and catheter-induced spasm [n=1]). Conclusions— Epicardial and microvascular spasm are frequently found in white patients with unobstructed coronary arteries. Epicardial spasm is most often diffuse and located in the distal coronary segments. The intracoronary acetylcholine provocation test is a safe technique to assess coronary vasomotor function.

3-year follow-up of patients with coronary artery spasm as cause of acute coronary syndrome: the CASPAR (coronary artery spasm in patients with acute coronary syndrome) study follow-up.

OBJECTIVES We sought to determine the prognosis of patients with acute coronary syndrome without culprit lesion and proof of coronary spasm during 3 years of follow-up. BACKGROUND Coronary artery spasm has been identified as an alternative cause for acute coronary syndrome (ACS) in patients without culprit lesion. In the CASPAR (Coronary Artery Spasm as a Frequent Cause for Acute Coronary Syndrome) study, we recently showed that ∼50% of ACS patients without culprit lesion, in whom intracoronary acetylcholine provocation was performed, had coronary spasm. However, data on prognosis in these patients are sparse. METHODS After 3 years of follow-up, data regarding the following end points were obtained: death (cardiac and noncardiac), nonfatal myocardial infarction, and recurrent angina leading to repeated coronary angiography. The analysis focused on patients with a culprit lesion (n = 270) and patients without a culprit lesion (n = 76) but with acetylcholine provocation (total n = 346). RESULTS In patients without culprit lesion, there was no cardiac death or nonfatal myocardial infarction during follow-up; 1 patient died due to a noncardiac cause. However, 38 of 76 patients reported persistent angina requiring repeated angiography in 3 cases (3.9%). Thirty of 270 patients with culprit lesion died due to a cardiac cause (11.1%) and 13 due to a noncardiac cause (4.8%). Eleven patients had nonfatal myocardial infarction (4.1%) and 27 repeated angiography due to persistent or recurrent angina (10%). Patients with a culprit lesion had a higher mortality and more coronary events compared with those without (p < 0.0005, log-rank test). CONCLUSIONS ACS patients without culprit lesion and proof of coronary spasm have an excellent prognosis for survival and coronary events after 3 years compared with patients with obstructive ACS. However, persistent angina represents a challenging problem in these patients, leading in some cases to repeated coronary angiography.

International standardization of diagnostic criteria for vasospastic angina

The Coronary Vasomotion Disorders International Study Group (COVADIS) was established to develop international standards for the diagnostic criteria of coronary vasomotor disorders. The first symposium held on the 4-5 September 2013 addressed the criteria for vasospastic angina, which included the following (i) nitrate-responsive angina, (ii) transient ischaemic electrocardiogram changes, and (iii) documented coronary artery spasm. Adoption of these diagnostic criteria will improve the clinical diagnosis of this condition and facilitate research in this field.

Cardiovascular magnetic resonance risk stratification in patients with clinically suspected myocarditis

BackgroundThe diagnosis of myocarditis is challenging due to its varying clinical presentation. Since myocarditis can be associated with significant 5-year mortality, and postmortem data show myocarditis in almost 10% of all adults suffering sudden cardiac death, individual risk stratification for patients with suspected myocarditis is of great clinical interest. We sought to demonstrate that patients with clinically suspected myocarditis and a normal cardiovascular magnetic resonance (CMR) according to our definition have a good prognosis, independent of their clinical symptoms and other findings.MethodsProspective clinical long-term follow-up of consecutive patients undergoing CMR for work-up of clinically suspected myocarditis at our institution in 2007-2008.ResultsFollow-up was available for n = 405 patients (all-comers, 54.8% inpatients, 38% outpatient referrals from cardiologists). Median follow-up time was 1591 days. CMR diagnosis was “myocarditis” in 28.8%, “normal” in 55.6% and “other pathology” in 15.6%. Normal CMR was defined as normal left ventricular (LV) volumes and normal left ventricular ejection fraction (LV-EF) in the absence of late Gadolinium Enhancement (LGE). The overall mortality was 3.2%. There were seven cardiac deaths during follow-up, in addition one aborted SCD and two patients had appropriate internal cardioverter defibrillator (ICD) shocks – all of these occurred in patients with abnormal CMR. Kaplan-Meier analysis with log-rank test showed significant difference for major adverse cardiac events (cardiac death, sudden cardiac death (SCD), ICD discharge, aborted SCD) between patients with normal and abnormal CMR (p = 0.0003).ConclusionIn our unselected population of consecutive patients referred for CMR work-up of clinically suspected myocarditis, patients with normal CMR have a good prognosis independent of their clinical symptoms and other findings.

The parallel tales of microvascular angina and heart failure with preserved ejection fraction: a paradigm shift

An increasing number of studies clearly demonstrate that coronary microvascular dysfunction (CMD) plays a pivotal role in several cardiovascular diseases.1 In particular, emerging evidence suggests that CMD is the main contributor to myocardial ischaemia in a large subset of patients with chronic stable angina. Indeed, non-obstructive coronary atherosclerosis is observed in up to 50% of patients with angina and positive stress test results undergoing diagnostic coronary angiography.2 Thus, the prevalence of microvascular angina (MVA) is higher than previously thought and associated with worse clinical outcomes than those observed in asymptomatic subjects with similar risk factor burden.3 The diagnosis of MVA is based on the following criteria: (i) symptoms of myocardial ischaemia; (ii) absence of obstructive epicardial coronary artery disease; (iii) evidence of myocardial ischaemia on non-invasive stress testing; and (iv) evidence of impaired coronary microvascular function. The clinical relevance of MVA has historically been overlooked since the diagnostic tools required for the evaluation of the coronary microcirculation are infrequently utilized. A parallel ‘tale’ could be proposed for heart failure (HF) with preserved ejection fraction (HFpEF). Indeed, HFpEF is observed in about 50% of patients presenting with HF symptoms and is characterized by the absence of a relevant reduction of left ventricular ejection fraction (LVEF).4 As with MVA, patients with HFpEF have poorer clinical outcomes compared with asymptomatic subjects exhibiting a similar burden of risk factors. The diagnosis of HFpEF is based on the following: (i) symptoms with or without signs of HF; (ii) normal or only mildy reduced LVEF; (iii) elevated levels of natriuretic peptides; (iv) relevant structural heart disease (i.e. left ventricular hypertrophy, left atrial enlargement) and/or diastolic dysfunction. In both MVA and HFpEF, no therapeutic intervention has hitherto been proven to improve patient outcome; similarly, symptomatic treatment is largely empirical. A key shared characteristic …