Catecholaminergic Polymorphic Ventricular Tachycardia: Clinical Characteristics, Diagnostic Evaluation and Therapeutic Strategies.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe hereditary arrhythmia syndrome predominantly affecting children and young adults. It manifests through bidirectional or polymorphic ventricular arrhythmia, often culminating in syncope triggered by physical exertion or emotional stress which can lead to sudden cardiac death. Most cases stem from mutations in the gene responsible for encoding the cardiac ryanodine receptor (RyR2), or in the Calsequestrin 2 gene (CASQ2), disrupting the handling of calcium ions within the cardiac myocyte sarcoplasmic reticulum. Diagnosing CPVT typically involves unmasking the arrhythmia through exercise stress testing. This diagnosis emerges in the absence of structural heart disease by cardiac imaging and with a normal baseline electrocardiogram. Traditional first-line treatment primarily involves ß-blocker therapy, significantly reducing CPVT-associated mortality. Adjunctive therapies such as moderate exercise training, flecainide, left cardiac sympathetic denervation and implantable cardioverter-defibrillators have been utilized with reasonable success. However, the spectrum of options for managing CPVT has expanded over time, demonstrating decreased rates of arrhythmic events. Furthermore, ongoing research into potential new therapies including gene therapies has the potential to further enhance treatment paradigms. This review aims to succinctly encapsulate the contemporary understanding of the clinical characteristics, diagnostic approach, established therapeutic interventions and the promising future directions in managing CPVT.

Early Clinical Outcomes of Patients With Stress-Induced Cardiomyopathy Receiving Acute Mechanical Support in the US.

Background: The role of acute mechanical circulatory support (aMCS) in patients with stress-induced cardiomyopathy (SIC) complicated by cardiogenic shock (CS) is not well studied. Here, we describe the incidence and outcomes of aMCS use in SIC-CS using a large national database. Methods: Using the Nationwide Readmissions Database from January 2016 to November 2019, we identified patients hospitalized with SIC who received isolated intra-aortic balloon pump (IABP), microaxial flow pump (Impella, Abiomed), or extracorporeal membrane oxygenation (ECMO) during the index hospitalization. Results: A total of 902 among 94,709 hospitalizations for SIC (1.0%) required aMCS during the index hospitalization: 611 had IABP (67.7%), 189 had Impella (21.0%) and 102 had ECMO (11.3%). Patients with ECMO or Impella had higher in-hospital mortality rates than those with IABP (37.3% vs 29.1% vs 18.5%, respectively). There was an increased adjusted risk of in-hospital death with Impella (adjusted odds ratio [aOR], 1.98; 95% CI, 1.12-3.49) and ECMO (aOR, 4.15; 95% CI, 1.85-9.32) vs IABP. Impella was associated with an increased adjusted risk of 30-day readmission compared to IABP (aOR, 2.53; 95% CI, 1.16-5.51). Patients with ECMO or Impella had a higher incidence of renal replacement therapy and vascular/bleeding complications compared to those who received IABP. Conclusions: In this nationwide analysis using an administrative database, patients who received ECMO and Impella showed higher rates of in-hospital mortality, renal replacement therapy, and vascular/bleeding complications compared to those who received IABP. Patients with more comorbidities may receive more aggressive hemodynamic support which may account for observed mortality differences. Future prospective studies with objective and universal characterization of baseline clinical and hemodynamic characteristics of patients with CS secondary to SIC are needed.

Determining the Significance of Coronary Plaque Lesions: Physiological Stenosis Severity and Plaque Characteristics.

The evaluation of coronary lesions has evolved in recent years. Physiologic-guided revascularization (particularly with pressure-derived fractional flow reserve (FFR)) has led to superior outcomes compared to traditional angiographic assessment. A greater importance, therefore, has been placed on the functional significance of an epicardial lesion. Despite the improvements in the limitations of angiography, insights into the relationship between hemodynamic significance and plaque morphology at the lesion level has shown that determining the implications of epicardial lesions is rather complex. Investigators have sought greater understanding by correlating ischemia quantified by FFR with plaque characteristics determined on invasive and non-invasive modalities. We review the background of the use of these diagnostic tools in coronary artery disease and discuss the implications of analyzing physiological stenosis severity and plaque characteristics concurrently.

Invasive Evaluation of the Microvasculature in Acute Myocardial Infarction: Coronary Flow Reserve versus the Index of Microcirculatory Resistance.

Acute myocardial infarction (AMI) is one of the most common causes of death in both the developed and developing world. It has high associated morbidity despite prompt institution of recommended therapy. The focus over the last few decades in ST-segment elevation AMI has been on timely reperfusion of the epicardial vessel. However, microvascular consequences after reperfusion, such as microvascular obstruction (MVO), are equally reliable predictors of outcome. The attention on the microcirculation has meant that traditional angiographic/anatomic methods are insufficient. We searched PubMed and the Cochrane database for English-language studies published between January 2000 and November 2019 that investigated the use of invasive physiologic tools in AMI. Based on these results, we provide a comprehensive review regarding the role for the invasive evaluation of the microcirculation in AMI, with specific emphasis on coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR).

Complete versus culprit-only revascularisation in ST elevation myocardial infarction with multi-vessel disease.

BACKGROUND: Multi-vessel coronary disease in people with ST elevation myocardial infarction (STEMI) is common and is associated with worse prognosis after STEMI. Based on limited evidence, international guidelines recommend intervention on only the culprit vessel during STEMI. This, in turn, leaves other significantly stenosed coronary arteries for medical therapy or revascularisation based on inducible ischaemia on provocative testing. Newer data suggest that intervention on both the culprit and non-culprit stenotic coronary arteries (complete intervention) may yield better results compared with culprit-only intervention. OBJECTIVES: To assess the effects of early complete revascularisation compared with culprit vessel only intervention strategy in people with STEMI and multi-vessel coronary disease. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, World Health Organization International Clinical Trials Registry Platform Search Portal, and ClinicalTrials.gov. The date of the last search was 4 January 2017. We applied no language restrictions. We handsearched conference proceedings to December 2016, and contacted authors and companies related to the field. SELECTION CRITERIA: We included only randomised controlled trials (RCTs), wherein complete revascularisation strategy was compared with a culprit-only percutaneous coronary intervention (PCI) for the treatment of people with STEMI and multi-vessel coronary disease. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of each trial using the Cochrane 'Risk of bias' tool. We resolved the disagreements by discussion among review authors. We followed standard methodological approaches recommended by Cochrane. The primary outcomes were long-term (one year or greater after the index intervention) all-cause mortality, long-term cardiovascular mortality, long-term non-fatal myocardial infarction, and adverse events. The secondary outcomes were short-term (within the first 30 days after the index intervention) all-cause mortality, short-term cardiovascular mortality, short-term non-fatal myocardial infarction, revascularisation, health-related quality of life, and cost. We analysed data using fixed-effect models, and expressed results as risk ratios (RR) with 95% confidence intervals (CI). We used GRADE criteria to assess the quality of evidence and we conducted Trial Sequential Analysis (TSA) to control risks of random errors. MAIN RESULTS: We included nine RCTs, that involved 2633 people with STEMI and multi-vessel coronary disease randomly assigned to either a complete (n = 1381) versus culprit-only (n = 1252) revascularisation strategy. The complete and the culprit-only revascularisation strategies did not differ for long-term all-cause mortality (65/1274 (5.1%) in complete group versus 72/1143 (6.3%) in culprit-only group; RR 0.80, 95% CI 0.58 to 1.11; participants = 2417; studies = 8; I2 = 0%; very low quality evidence). Compared with culprit-only intervention, the complete revascularisation strategy was associated with a lower proportion of long-term cardiovascular mortality (28/1143 (2.4%) in complete group versus 51/1086 (4.7%) in culprit-only group; RR 0.50, 95% CI 0.32 to 0.79; participants = 2229; studies = 6; I2 = 0%; very low quality evidence) and long-term non-fatal myocardial infarction (47/1095 (4.3%) in complete group versus 70/1004 (7.0%) in culprit-only group; RR 0.62, 95% CI 0.44 to 0.89; participants = 2099; studies = 6; I2 = 0%; very low quality evidence). The complete and the culprit-only revascularisation strategies did not differ in combined adverse events (51/2096 (2.4%) in complete group versus 57/1990 (2.9%) in culprit-only group; RR 0.84, 95% CI 0.58 to 1.21; participants = 4086; I2 = 0%; very low quality evidence). Complete revascularisation was associated with lower proportion of long-term revascularisation (145/1374 (10.6%) in complete group versus 258/1242 (20.8%) in culprit-only group; RR 0.47, 95% CI 0.39 to 0.57; participants = 2616; studies = 9; I2 = 31%; very low quality evidence). TSA of long-term all-cause mortality, long-term cardiovascular mortality, and long-term non-fatal myocardial infarction showed that more RCTs are needed to reach more conclusive results on these outcomes. Regarding long-term repeat revascularisation more RCTs may not change our present result. The quality of the evidence was judged to be very low for all primary and the majority of the secondary outcomes mainly due to risk of bias, imprecision, and indirectness. AUTHORS' CONCLUSIONS: Compared with culprit-only intervention, the complete revascularisation strategy may be superior due to lower proportions of long-term cardiovascular mortality, long-term revascularisation, and long-term non-fatal myocardial infarction, but these findings are based on evidence of very low quality. TSA also supports the need for more RCTs in order to draw stronger conclusions regarding the effects of complete revascularisation on long-term all-cause mortality, long-term cardiovascular mortality, and long-term non-fatal myocardial infarction.

Stroke and a valvular lesion in a patient with stage IV non-small cell lung cancer.

The mechanism and severity of stroke varies in the setting of malignancy. We report a case of a 68-year-old man with lung adenocarcinoma, who experienced acute neurological symptoms. Imaging studies showed multiple acute ischaemic infarcts in cerebral and cerebellar hemispheres. Further work up was consistent with non-bacterial thrombotic endocarditis (NBTE). We highlight, through a review of the literature, the importance of transoesophageal echocardiography (TOE) in defining the above diagnosis. The treatment of NBTE consists of systemic anticoagulation and therapy of the underlying malignancy. Enoxaparin is preferred over warfarin to achieve this goal. He received systemic targeted therapy with erlotinib. A TOE performed 8 months later showed complete resolution of the vegetation.

Life-threatening hyperkalemia: a potentially lethal drug combination.

Hyperkalemia is commonly seen in the elderly and is occasionally fatal. Inadvertently combining potassium sparing medications can result in profound hyperkalemia which may result in cardiac dysrhythmias, especially in the setting of chronic kidney disease. An 85 year-old woman on a drug regimen of sotalol, valsartan, spironolactone, and trimethoprim-sulfamethoxazole presented to the emergency department with hypotension and bradycardia. Presumptive treatment for hyperkalemia was started based on her initial electrocardiogram. This diagnosis was later confirmed with a serum potassium value of 10.1 mmol/L. Following pharmacologic treatment, emergency hemodialysis was performed and the patient subsequently recovered. It is known that several drug classes can cause hyperkalemia, with elderly patients at a higher risk of developing this side effect. It is believed that this was a major contributor to the degree of hyperkalemia seen in this patient.

Serial evaluation of microcirculatory dysfunction in patients with Takotsubo cardiomyopathy by myocardial contrast echocardiography.

BACKGROUND: Stress cardiomyopathy manifests as reversible left ventricular apical ballooning in the absence of epicardial coronary obstruction. Transient microcirculatory dysfunction has been proposed as a potential putative mechanism. This study aimed to understand the natural history of this dysfunction using readily available noninvasive methods. HYPOTHESIS: Stress cardiomyopathy presents with profound microvascular dysfunction that improves quickly over a period of 3 to 4 weeks. METHODS: Nine consecutive patients with Takotsubo cardiomyopathy were followed serially with myocardial perfusion echocardiograms at 24 hours, within 1 week, and 3 to 6 months after index admission. RESULTS: The mean left ventricular ejection fraction (LVEF) steadily improved from 38% at baseline to 48% within 1 week to 67% by the end of 3 to 6 months follow-up. The number of wall segments with reduced or absent perfusion decreased from 4.1 at baseline to 2 at 1 week. By 3 to 6 months, perfusion had returned to normal in all but 1 segment in 1 patient. At 1 week, the relative improvement in mean LVEF was 26%, whereas perfusion had improved by nearly 50%, suggesting a fairly pronounced improvement in microcirculatory function prior to recovery of wall motion. CONCLUSIONS: Patients with Takotsubo cardiomyopathy present with significant acute microcirculatory dysfunction that recovers quickly prior to the recovery of regional wall motion abnormalities.

Validity of Amino Terminal pro-Brain Natiuretic Peptide in a Medically Complex Elderly Population.

BACKGROUND: The routine use of natiuretic peptides in severely dyspneic patients has recently been called into question. We hypothesized that the diagnostic utility of Amino Terminal pro Brain Natiuretic Peptide (NT-proBNP) is diminished in a complex elderly population. METHODS: We studied 502 consecutive patients in whom NT-proBNP values were obtained to evaluate severe dyspnea in the emergency department. The diagnostic utility of NT-proBNP for the diagnosis of congestive heart failure (CHF) was assessed utilizing several published guidelines, as well as the manufacturers suggested age dependent cut-off points. RESULTS: The area under the receiver operator curve (AUC) for NT-proBNP was 0.70. Using age-related cut points, the diagnostic accuracy of NT-proBNP for the diagnosis of CHF was below prior reports (70% vs. 83%). Age and estimated creatinine clearance correlated directly with NT-proBNP levels, while hematocrit correlated inversely. Both age > 50 years and to a lesser extent hematocrit < 30% affected the diagnostic accuracy of NT-proBNP, while renal function had no effect. In multivariate analysis, a prior history of CHF was the best predictor of current CHF, odds ratio (OR) = 45; CI: 23-88. CONCLUSIONS: The diagnostic accuracy of NT-proBNP for the evaluation of CHF appears less robust in an elderly population with a high prevalence of prior CHF. Age and hematocrit levels, may adversely affect the diagnostic accuracy off NT-proBNP. KEYWORDS: Congestive Heart Failure; Natriuretic peptides; Diagnosis; Elderly Patients.

Does choice of antidiabetes therapy influence macrovascular outcomes?

Despite a clear epidemiologic relationship between hemoglobin A(1c) levels and the risk of cardiovascular (CV) disease in patients with type 2 diabetes mellitus (T2DM), prospective studies examining the benefit of intensive glucose lowering in reducing CV events have yielded conflicting results. Controversy over the choice of antidiabetic therapy for lowering macrovascular events has existed for nearly four decades, beginning with the potential risk of increased CV mortality with sulfonylurea use. Although sulfonylureas were subsequently felt to be safe, a more recent controversy was raised as to whether rosiglitazone use was associated with an increased risk of CV events. Additionally, early positive results for metformin in reducing macrovascular events have not been clearly substantiated. Because a typical patient with T2DM may live 20 to 40 years with the disease, long-term prevention of CV events is very important. An evidenced-based review of choice of antidiabetic therapy to reduce CV events in T2DM is discussed below.

Antidiabetic agents and cardiovascular risk in type 2 diabetes.

Despite the clear relationship between HbA(1c) levels and risk of cardiovascular disease in patients with type 2 diabetes mellitus (T2DM) in epidemiologic studies, prospective data on the role of glucose-lowering therapy in reducing cardiovascular events are equivocal. Initial studies of intensive glycemic control suffered from inadequate statistical power to show reductions in cardiovascular events, as well as a lack of durable glycemic control and relatively poor control of associated cardiovascular risk factors. Subsequently, controversy existed over whether rosiglitazone was associated with an increased risk of myocardial ischemic events. Large, prospective, cardiovascular outcome trials that assessed intensive glycemic control versus standard glycemic control have had disappointing results; however, cardiovascular event rates seem to be declining substantially in patients with T2DM managed with aggressive global cardiovascular risk factor modification, which might have masked the benefits of glycemic control. Individuals with T2DM without a history of cardiovascular disease, as well as younger individuals with more modest elevations of HbA(1c), may benefit from a more intensive glucose-lowering strategy. A comprehensive and multifactorial intervention strategy that includes aggressive glycemic control, blood-pressure-lowering and lipid-lowering therapy, aspirin use and lifestyle modifications is beneficial in reducing both macrovascular and microvascular events in patients with T2DM.

Potential of glucose-lowering drugs to reduce cardiovascular events.

Although a clear relationship exists between glycosylated hemoglobin and cardiovascular (CV) disease in individuals with type 2 diabetes mellitus (T2DM) in epidemiologic studies, data from prospective studies are less clear. Earlier prospective studies examining intensive glucose lowering suffered from a lack of statistical power to show CV event reduction, as well as a lack of durable glycemic control and relatively poor control of associated CV risk factors. Although recent CV outcome trials comparing intensive glycemic compared with standard glycemic control have been disappointing, CV event rates appear to be declining substantially in T2DM individuals in the setting of aggressive global CV risk factor modification. No single hypoglycemic agent or combination of agents was associated with increased CV events or mortality. A comprehensive strategy of multifactorial intervention including aggressive and durable glycemic blood pressure, and lipid lowering, aspirin usage, and lifestyle modifications is beneficial in reducing macrovascular and microvascular events in T2DM individuals.

Lowering glucose to prevent adverse cardiovascular outcomes in a critical care setting.

High admission blood glucose levels after acute myocardial infarction are common and associated with an increased risk of death in patients with or without diabetes. Hyperglycemia is associated with altered myocardial blood flow and energetics and can lead to a pro-oxidative/proinflammatory state. The use of intensive insulin treatment has shown superior benefits in the treatment of hyperglycemia versus glucose-insulin-potassium infusion, particularly in critical care settings.

The role of aspirin resistance in the treatment of acute coronary syndromes.

The TIMI Risk Score recognizes prior aspirin use as an independent risk factor for adverse outcomes in subjects presenting with an acute coronary syndrome. The etiology of this increased risk awaits clarification, but prior aspirin use may be associated with altered thrombus composition which is more resistant to current treatment modalities as compared to thrombus formation in subjects without prior aspirin use. Post hoc analysis of acute coronary syndrome trials has shown that prior aspirin users treated with unfractionated heparin are at particularly high risk. The addition of glycoprotein IIb/IIIa receptor inhibitor to unfractionated heparin or substitution of low-molecular-weight heparin significantly improves outcomes in prior aspirin users. The prognostic significance of prior aspirin use in acute coronary syndromes has important implications not only in clinical practice, but also in the design and interpretation of clinical trials.

The effect of a six-week program of yoga and meditation on brachial artery reactivity: do psychosocial interventions affect vascular tone?

BACKGROUND: Chronic stress is estimated to increase the risk of cardiovascular (CV) events two-fold. Although stress reduction has been linked to a reduction in CV events, little is known regarding its exact mechanism of benefit. HYPOTHESIS: Yoga and meditation will improve parameters of endothelial function. METHODS: We examined the effects of yoga and meditation on hemodynamic and laboratory parameters as well as on endothelial function in a 6-week pilot study. Systolic and diastolic blood pressures, heart rate, body mass index (BMI), fasting glucose, lipids, hs C-reactive protein (CRP), and endothelial function (as assessed by brachial artery reactivity) were all studied at baseline and after 6 weeks of yoga practice. RESULTS: A course in yoga and meditation was given to the subjects for 1.5 h three times weekly for 6 weeks and subjects were instructed to continue their efforts at home. This prospective cohort study included 33 subjects (mean age 55 +/- 11 years) both with (30%) and without (70%) established coronary artery disease (CAD). There were significant reductions in blood pressure, heart rate, and BMI in the total cohort with yoga. None of the laboratory parameters changed significantly with yoga. For the total cohort there was no significant improvement in endothelial-dependent vasodilatation with yoga training and meditation compared with baseline (16.7% relative improvement from 7.2-8.4%; p = 0.3). In the group with CAD, endothelial-dependent vasodilatation improved 69% with yoga training (6.38-10.78%; p = 0.09). CONCLUSION: Yoga and meditation appear to improve endothelial function in subjects with CAD.

Mechanism by which hyperglycemia plays a role in the setting of acute cardiovascular illness.

Acute hyperglycemia is associated with excess morbidity and mortality in acute cardiovascular illness in both diabetic and nondiabetic patients. Hyperglycemia is associated with altered myocardial energetics, but abnormalities in glucose oxidation and glycolysis do not fully account for this excess risk. Hyperglycemia leads to a pro-oxidative/proinflammatory state that is associated with endothelial dysfunction, diminished coronary vasodilatory reserve, and a prothrombotic state. Hyperglycemia negates the protective effect of ischemic preconditioning and, most importantly, appears to interfere with the salutary effects of insulin in acute cardiovascular illness. Aggressive therapy with continuous infusion of insulin seems to improve a host of metabolic and physiologic effects associated with acute hyperglycemia and appears warranted if euglycemia can be maintained.