Substance Withdrawal-Associated Takotsubo Cardiomyopathy: A Review of the Literature.

Objective: To better understand Takotsubo cardiomyopathy, a rare but life-threatening complication of acute substance withdrawal.Data Sources: A PubMed search was conducted to identify relevant case reports through 2021 using the medical subject headings alcohol withdrawal, opioid withdrawal, benzodiazepine withdrawal OR withdrawal AND Takotsubo OR stress cardiomyopathy.Study Selection: Case reports were included in the review if there was a diagnosis of Takotsubo cardiomyopathy in the setting of withdrawal from substances of abuse. Case reports were excluded if patients were withdrawing from other substances, actively intoxicated, or had myocardial ischemia.Data Extraction and Synthesis: Data were manually abstracted for the variables of interest, including demographics, symptoms, medical evaluation, and treatment. Descriptive statistics of the demographics, symptoms, medical evaluation, and treatment of Takotsubo cardiomyopathy were analyzed.Results: The mean (SD) age of patients experiencing withdrawal-associated Takotsubo cardiomyopathy was 50.8 years (15.2), and 64% of patients were female. The most common signs and symptoms were tachycardia (60%), changes in blood pressure (48%), altered mental status (48%), dyspnea (32%), nausea or vomiting (28%), and chest pain (28%). All patients with a reported electrocardiogram (92%) demonstrated ECG abnormalities; 76% had an elevated troponin level, and 24% had an elevated CK-MB level. Medications that could treat withdrawal and α2-agonists were utilized for 60% and 12% of patients, respectively. Ventilator support, cardiopulmonary resuscitation, and intra-aortic balloon pump were needed for 24%, 8%, and 8%, respectively, of patients with withdrawal-associated Takotsubo cardiomyopathy.Conclusions: Withdrawal-associated Takotsubo cardiomyopathy is a rare but potentially life-threatening complication of substance withdrawal. Clinicians should maintain a high degree of clinical suspicion for withdrawal-associated Takotsubo in patients with a history of substance use disorders or physical dependence on benzodiazepines or opioids, as the clinical presentation may be atypical.

Risk Stratification of Sudden Cardiac Death After Acute Myocardial Infarction.

Despite advances in the diagnosis and treatment of acute coronary syndromes and an overall improvement in outcomes, mortality after myocardial infarction (MI) remains high. Sudden death, which is most frequently due to ventricular tachycardia or ventricular fibrillation, is the cause of death in 25% to 50% of patients with prior MI, and therefore represents an important public health problem. Use of the implantable cardioverter-defibrillator (ICD), which is the primary method of reducing the chance of arrhythmic sudden death after MI, is costly to the medical system and is associated with procedural and long-term risks. Additionally, assessment of left ventricular ejection fraction (LVEF), which is the primary method of assessing a patient's post-MI sudden death risk and appropriateness for ICD implantation, lacks both sensitivity and specificity for sudden death, and may not be the optimal way to select the subgroup of post-MI patients who are most likely to benefit from ICD implantation. To optimally utilize ICDs, it is therefore critical to develop and prospectively validate sudden death risk stratification methods beyond measuring LVEF. A variety of tests that assess left ventricular systolic function/morphology, potential triggers for ventricular arrhythmias, ventricular conduction/repolarization, and autonomic tone have been proposed as sudden death risk stratification tools. Multivariable models have also been developed to assess the competing risks of arrhythmic and non-arrhythmic death so that ICDs can be utilized more effectively. This manuscript will review the epidemiology of sudden death after MI, and will discuss the current state of sudden death risk stratification in this population.

Increased myocardial native T1 relaxation time in patients with nonischemic dilated cardiomyopathy with complex ventricular arrhythmia.

PURPOSE: To study the relationship between diffuse myocardial fibrosis and complex ventricular arrhythmias (ComVA) in patients with nonischemic dilated cardiomyopathy (NICM). We hypothesized that NICM patients with ComVA would have a higher native myocardial T1 time, suggesting more extensive myocardial diffuse fibrosis. MATERIALS AND METHODS: We prospectively enrolled NICM patients with a history of ComVA (n = 50) and age-matched NICM patients without ComVA (n = 57). Imaging was performed at 1.5T with a protocol that included cine magnetic resonance imaging (MRI) for left ventricular (LV) function, late gadolinium enhancement (LGE) for focal scar, and native T1 mapping for diffuse fibrosis assessment. RESULTS: Global native T1 time was significantly higher in patients with NICM with ComVA when compared to patients with NICM without ComVA (1131 ± 42 vs. 1107 ± 45 msec, P = 0.006), and this finding remained after excluding segments with scar on LGE (1124 ± 36 vs. 1102 ± 44 msec, P = 0.006). Native T1 was similar in NICM patients with and without the presence of LGE (1121 ± 39 vs. 1117 ± 48 msec, P = 0.68) and mildly correlated with LV end-diastolic volume index (r = 0.27, P = 0.005), LV end-systolic volume index (r = 0.24, P = 0.01), and LV ejection fraction (r = -0.28, P = 0.003). Native T1 value for each 10-msec increment was an independent predictor of ComVA (odds ratio 1.14, 95% confidence interval 1.03-1.25; P = 0.008) beyond LV function and LGE. CONCLUSION: NICM patients with ComVA have higher native T1 compared to NICM without any documented ComVA. Native myocardial T1 is independently associated with ComVA, after adjusting for LV function and LGE. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:779-786. In memoriam: The authors are grateful for Dr. Josephson's inspiring guidance and contributions to this study.

Diffuse myocardial fibrosis in patients with mitral valve prolapse and ventricular arrhythmia.

OBJECTIVE: We aimed to investigate the association of diffuse myocardial fibrosis by cardiac magnetic resonance (CMR) T1 with complex ventricular arrhythmia (ComVA) in mitral valve prolapse (MVP). METHODS: A retrospective analysis was performed on 41 consecutive patients with MVP referred for CMR between 2006 and 2011, and 31 healthy controls. Arrhythmia analysis was available in 23 patients with MVP with Holter/event monitors. Left ventricular (LV) septal T1 times were derived from Look-Locker sequences after administration of 0.2 mmol/kg gadopentetate dimeglumine. Late gadolinium enhancement (LGE) CMR images were available for all subjects. RESULTS: Patients with MVP had significantly shorter postcontrast T1 times when compared with controls (334±52 vs 363±58 ms; p=0.03) despite similar LV ejection fraction (LVEF) (63±7 vs 60±6%, p=0.10). In a multivariable analysis, LV end-diastolic volume, LVEF and mitral regurgitation fraction were all correlates of T1 times, with LVEF and LV end-diastolic volume being the strongest (p=0.005, p=0.008 and p=0.045, respectively; model adjusted R2=0.30). Patients with MVP with ComVA had significantly shorter postcontrast T1 times when compared with patients with MVP without ComVA (324 (296, 348) vs 354 (327, 376) ms; p=0.03) and only 5/14 (36%) had evidence of papillary muscle LGE. CONCLUSIONS: MVP may be associated with diffuse LV myocardial fibrosis as suggested by reduced postcontrast T1 times. Diffuse interstitial derangement is linked to subclinical systolic dysfunction, and may contribute to ComVA in MVP-related mitral regurgitation, even in the absence of focal fibrosis.

Relationship Between Early and Late Nonsustained Ventricular Tachycardia and Cardiovascular Death in Patients With Acute Coronary Syndrome in the Platelet Inhibition and Patient Outcomes (PLATO) Trial.

BACKGROUND: Nonsustained ventricular tachycardia (NSVT) is common after acute coronary syndrome (ACS) and a marker of increased risk of arrhythmogenic death. However, the prognostic significance of NSVT when evaluated with other contemporary risk markers and at later time points after ACS remains uncertain. METHODS AND RESULTS: In the Platelet Inhibition and Patient Outcomes (PLATO) trial, continuous ECGs were performed during the first 7 days after ACS (n=2866) and repeated for another 7 days at day 30 (n=1991). Median follow-up was 1 year. There was a time-varying interaction between NSVT and cardiovascular death such that NSVT was significantly associated with increased risk within the first 30 days after randomization (22/999 [2.2%] versus 16/1825 [0.9%]; adjusted hazard ratio, 2.84; 95% confidence interval, 1.39-5.79; P=0.004) but not after 30 days (28/929 [3.0%] versus 42/1734 [2.4%]; P=0.71). Detection of NSVT during the convalescent phase (n=428/1991; 21.5%) was also associated with an increased risk of cardiovascular death, and was most marked within the first 2 months after detection (1.9% versus 0.3%; adjusted hazard ratio, 5.48; 95% confidence interval, 1.07-28.20; P=0.01), and then decreasing over time such that the relationship was no longer significant by ≈5 months after ACS. CONCLUSIONS: NSVT occurred frequently during the acute and convalescent phases of ACS. The risk of cardiovascular death associated with NSVT was the greatest during the first 30 days after presentation; however, patients with NSVT detected during the convalescent phase were also at a significantly increased risk of cardiovascular death that persisted for an additional several months after the index event. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Neurologic adverse effects of ranolazine in an elderly patient with renal impairment.

Ranolazine, an antianginal agent, has activity at muscle and neuronal sodium channels. Congenital genetic mutations to sodium channels in humans and supratherapeutic ranolazine concentrations in animal models have produced similar neurologic adverse reactions. We describe a case of neurologic adverse effects in an 81-year-old woman with coronary artery disease, renal impairment, and mild neurologic disease who received ranolazine for symptomatic control of a non-ST-segment elevation myocardial infarction. Just over 48 hours after a dose increase, she experienced new-onset dysarthia, dysmetria, hallucinations, worse tremors, and difficulty with word finding. Her workup for acute stroke and infectious causes was negative. Her symptoms abated 2 days after ranolazine was discontinued. The patient was at risk for ranolazine adverse effects due to the high dose administered and her advanced age, renal impairment, and baseline mild neurologic disease. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's neurologic adverse events and the ranolazine therapy. To our knowledge, this is the first case report illustrating rare but debilitating neurologic adverse effects of ranolazine. Health care practitioners should be aware of the adverse effects of ranolazine and avoid doses greater than 500 mg twice/day in patients older than 80 years or those with a creatinine clearance of less than 30 ml/minute.

Elevated concentration of placental growth factor (PlGF) and long term risk in patients with acute coronary syndrome in the PROVE IT-TIMI 22 trial.

Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, acts via the flt-1 receptor and promotes endothelial activation and macrophage recruitment into atherosclerotic lesions. We investigated the relationship of PlGF with cardiovascular outcomes in a large cohort of patients presenting across the spectrum of ACS. PlGF was measured at baseline (n = 3,761) and at four-months (n = 3,369) in patients randomized to atorvastatin 80 mg or pravastatin 40 mg after ACS in the PROVE IT-TIMI 22 trial. The primary endpoint was death, myocardial infarction (MI), unstable angina, revascularization or stroke (mean follow-up 24 months). Elevated baseline PlGF was associated with a higher incidence of the primary endpoint through 2 years (Q1 vs. Q5: 18.7 vs. 29.3%, p < 0.0001). The risk of death or MI was also higher in patients with elevated baseline PlGF (Q1 vs. Q5: 7.0 vs. 11.6%, p = 0.029). Adjusting for baseline characteristics and risk factors, elevated baseline PlGF was independently associated with the risk of the primary endpoint (adjusted-HR for Q5 vs. Q1 1.45; 95% CI 1.16-1.83; p = 0.001). Elevated PlGF at four months was associated with higher risk of death or MI (Adjusted HR Q5 vs. Q1 2.79, 95% CI: 1.37-5.68; p = 0.005), and higher risk of the primary endpoint (Adjusted HR Q5 vs. Q1 1.78, 95% CI: 1.26-2.51; p = 0.001). Higher concentration of PlGF after ACS is associated with long-term risk of recurrent cardiovascular events independent of traditional risk factors. This association is present early after ACS and appears to be stronger at four months.