SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart.

Coronavirus disease (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The symptoms of the disease range from asymptomatic to mild respiratory symptoms and even potentially life-threatening cardiovascular and pulmonary complications. Cardiac complications include acute myocardial injury, arrhythmias, cardiogenic shock and even sudden death. Furthermore, drug interactions with COVID-19 therapies may place the patient at risk for arrhythmias, cardiomyopathy and sudden death. In this review, we summarise the cardiac manifestations of COVID-19 infection and propose a simplified algorithm for patient management during the COVID-19 pandemic.

Heart Transplantation in Giant Cell Myocarditis: Analysis of the United Network for Organ Sharing Registry.

BACKGROUND: Giant cell myocarditis (GCM) is a lethal, rapidly progressive disease, for which heart transplantation is the treatment of choice. We sought to describe the characteristics and outcomes of patients with GCM who undergo heart transplantation. METHODS AND RESULTS: We used the United Network for Organ Sharing thoracic organ transplantation registry to identify adults with GCM as the primary diagnosis and compared their characteristics and outcomes with patients who underwent transplantation for other types of myocarditis and for idiopathic dilated cardiomyopathy (IDCMP). A total of 32 patients with GCM were compared with 219 patients with myocarditis and 14,221 patients with IDCMP. Median age at listing for GCM was 52 years (interquartile range 40-55 y), and the majority were white (94%), male (63%), and listed as 1A (44%). Biventricular assist devices were used more frequently in GCM compared with IDCMP (31% vs 2%; P < .001). After transplantation, there were no statistically significant differences among GCM, myocarditis, and IDCMP patients regarding pacemaker implantation, dialysis initiation, or stroke rate. GCM patients had increased risk of acute rejection compared with IDCMP patients (16% vs 5.0%; P = .021) but no difference in rehospitalization for rejection among the 3 etiologies (P = .88). The cumulative survivals for GCM patients at 1, 5, and 10 years were 94%, 82%, and 68%, respectively, which was similar to the other etiologies (P = .11). CONCLUSIONS: Compared with patients with IDCMP, those with GCM present more acutely and have significantly higher utilization of biventricular mechanical circulatory support. Despite higher rates of early rejection, post-transplantation survival of patients with GCM was similar to that of other myocarditides and IDCMP.

Percutaneous Ventricular Restoration with a Partitioning Device for Ischemic Heart Failure Treatment.

PURPOSE OF THE REVIEW: Percutaneous ventricular restoration with a ventricular partitioning device (VPD) is a novel minimally invasive procedure designed to restore the left ventricular (LV) shape by isolating the infarcted and aneurysmal LV apex from remainder of the cavity in heart failure patients with severely reduced LV ejection fraction. In this review, we perform an in-depth analysis of the design and purpose of the VPD and review the available clinical data, with special attention to hemodynamics, outcomes, and complications. RECENT FINDINGS: PARACHUTE trials have shown >90% procedural success rate of VPD implant. Heart failure patients had improvement in hemodynamics (reduction in LV volumes and increase in LV ejection fraction) and functional status (6-min walking distance and quality of life scores) after the VPD implant. Optimal implant position is necessary to obtain a good clinical outcome. Percutaneous VPD implantation has thus far been a safe intervention capable of improving surrogate markers of heart failure but there is still a need to develop more durable devices with a long-lasting hemodynamics effect.

Exercise-induced pulmonary hypertension: physiological basis and methodological concerns.

Exercise stresses the pulmonary circulation through increases in cardiac output (.Q) and left atrial pressure. Invasive as well as noninvasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure (mPAP)-flow relationships ranges from 0.5 to 3 mm Hg.min.L(-1). The upper limit of normal mPAP at exercise thus approximates 30 mm Hg at a .Q of less than 10 L.min(-1) or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to PAP in a close to one-for-one mm Hg fashion. Multipoint PAP-flow relationships are usually described by a linear approximation, but present with a slight curvilinearity, which is explained by resistive vessel distensibility. When mPAP is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase .Q at the highest levels of exercise. Exercise has to be dynamic to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Postexercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in PAP to a mean higher than 30 mm Hg may be associated with dyspnea-fatigue symptomatology.

Left Bundle Branch Area Pacing From a Femoral Approach in a Patient Without Superior Access.

Limited venous access and lateral left ventricular scar are impediments to traditional cardiac resynchronization therapy. We present a case where placement of an implantable cardioverter-defibrillator from a femoral approach while using left bundle branch area pacing led to clinical improvement. (Level of Difficulty: Intermediate.).

Utility of Very High-Output Pacing to Identify VT Circuits in Patients Manifesting Traditionally Inexcitable Scar.

BACKGROUND: Entrainment and pace mapping are used to identify critical components (CCs) of ventricular tachycardia (VT) circuits. In patients with dense myocardial scarring, VT circuits may elude capture at standard high pacing outputs (up to 10 mA at a 2-millisecond pulse width). OBJECTIVES: The purpose of this study was to assess the utility of very high-output pacing (V-HOP, 50 mA at 2 milliseconds) for identifying CCs of VT circuits after standard high pacing output failed to elicit capture in densely scarred myocardial tissue. METHODS: Our standard VT ablation approach included electroanatomic mapping for substrate characterization and entrainment and/or pace mapping to identify CCs of VT circuits. Patients that required V-HOP to capture sites of interest comprised the study cohort. Ablation endpoints were VT termination and noninducibility. RESULTS: Twenty-five patients (71 ± 10 years of age, all males) undergoing 26 VT ablations met the inclusion criteria. The mean left ventricular ejection fraction was 30% ± 14%, and 85% had ischemic cardiomyopathy. V-HOP was used to successfully entrain VT in 17 patients, yielding central isthmus sites in 10 and entrance/exit sites in 4. VT terminated with radiofrequency ablation at these sites in 15 patients. In 9 patients, V-HOP identified scar locations with a delayed exit. Acute procedural success was achieved in 24 patients without any adverse events. Over a follow-up period of 16 ± 21 months, 2 patients experienced VT recurrence requiring repeat ablation during which the same location was targeted successfully in 1 patient. CONCLUSIONS: In VT patients with a dense scar that is traditionally inexcitable, V-HOP can identify CCs of the re-entrant circuit and guide successful ablation.

Loss of Right Atrial Pacing Lead Capture Due to Myocardial Infarction Obscuring Diagnosis on Electrocardiogram.

Right coronary artery occlusion can lead to failure to capture from the right atrial pacing lead. In this case, acute infarction resulted in failure of the right atrial lead to capture and thus increased right ventricular pacing. The new ventricular pacing masked the diagnosis of acute myocardial infarction. (Level of Difficulty: Intermediate.).

Relation of Pretransplant Peak Oxygen Consumption to Outcomes After Heart Transplantation.

Peak exercise oxygen consumption (pVO2) is an important predictor of prognosis in patients with heart failure (HF). The association between pretransplant pVO2 and post-transplantation outcomes in HF patients has not been previously studied. We identified adult OHT recipients with available pVO2 in the United Network for Organ Sharing registry (2000 to 2015). Patients were divided into 3 categories using Weber classification: class B (pVO2 16 to 20 ml/kg/min), class C (pVO2 10 to 16 ml/kg/min), and class D (pVO2 <10 ml/kg/min). Postoperative outcomes (mortality, renal failure, rejection) were compared between the groups. A total of 9,623 patients were included in this analysis; the mean age was 54 ± 11 years, 74% were male, 75% were white and 59% had nonischemic etiology of HF. The mean pVO2 was 11.7 ± 3.6 ml/kg/min: 1,202 (12.5%) in class B, 6,055 (62.9%) in class C, and 2,366 (24.6%) were in class D. At a median follow-up of 6.1 years, 2,730 (28.4%) died. Post-transplantation survival decreased with decreasing pVO2; 1 and 5-year survival: B (92%, 80%), C (90%, 79%), and D (87%, 75%), p <0.001 by log-rank. After multiple adjustments, patients in class D had significantly higher post-transplantation mortality compared with class C (Hazard Ratio (HR) 1.21 [1.03 to 1.43], p = 0.02). When analyzed as a continuous variable, each 1 ml/kg/min increase in pVO2 was associated with 2% decrease in mortality during follow-up (adjusted HR 0.98 [0.96 to 0.99], p <0.001). Patients in class D had significantly prolonged (>14 days) hospitalization (adjusted Odds Ratio (OR) 1.42 [1.20 to 1.68], p <0.001) and a trend toward increased need for dialysis (adjusted OR 1.36 [1.00 to 1.84], p = 0.05) compared with patients in class B. In this large cohort, lower pretransplant pVO2 was associated with greater mortality and morbidity after OHT. These results suggest that earlier transplantation might improve post-transplantation outcomes in advanced HF patients.

Outcomes of Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention Analysis of National Inpatient Sample.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia with a prevalence of 15% of patients over 80 years. Coronary artery disease co-exists in 20-30% of patients with atrial fibrillation. The need for triple anticoagulation therapy makes the management of these patients challenging following PCI. METHODS: Nationwide inpatient sample which is a set of longitudinal hospital inpatient databases was used to evaluate the outcome of patients with AF who underwent PCI. All patients undergoing PCI between 2002 and 2011 were included in the study. Specific ICD-9-CM codes were used to identify the study patients and their outcomes. RESULTS: There were 3,226,405 PCIs during the time period of the study of which 472,609 (14.6%) patients had AF. AF patients were older and predominantly male (60%). The number of PCIs had a declining trend from 2002 to 2011. Age adjusted inpatient mortality was significantly higher in PCI AF group compared to the PCI non-AF group (100.82 ±â€¯9.03 vs 54.07 ±â€¯8.96 per 100,000; P < 0.01). Post PCI predictors of mortality were AF (OR 1.56, CI 1.53-1.59), CKD (OR 1.41, CI 1.37-1.46), PAD (OR 1.20, CI 1.15-1.24), acute myocardial infarction (OR 2.42 CI 2.37-2.46 and cardiogenic shock (OR 13.92 CI 13.60-14.24) P < 0.001. CONCLUSION: AF is common in patients undergoing PCI and those AF patients have a higher age-adjusted all cause inpatient mortality. There is a decline in total number of PCIs over time in US. Atrial fibrillation, chronic kidney disease, peripheral artery disease, MI and cardiogenic shock were associated with increased mortality following PCI.

Arrhythmias in Relation to Mortality After Transcatheter Aortic Valve Replacement.

BACKGROUND: The purpose of this study was to identify predictors of mortality and potentially modifiable factors related to arrhythmias in patients that undergo transcatheter aortic valve replacement (TAVR). Patients that undergo TAVR are at risk for complete heart block requiring pacemaker implant. Additionally, other arrhythmias, specifically atrial fibrillation (AF), are common in this population. It is unclear how arrhythmias and their management contribute to mortality risk. METHODS: The study analyzed 176 patients who underwent TAVR at a single center. Factors associated with pacemaker implantation within 30 days were analyzed by logistic regression. Factors associated with mortality were analyzed by Kaplan-Meier and Cox regression analyses. RESULTS: Mean age was 80 ± 8.5 years. AF was present in 69 patients, and 39 received anticoagulation. Post-TAVR, a pacemaker was implanted in 25 patients within 30 days. Over a follow up of 566 ± 496 days, 49 patients died. In multivariable analysis, right bundle branch block remained significant (odds ratio 4.212, P = 0.012) for pacemaker implant within 30 days. The AF (hazard ratio [HR] 3.905, P = 0.001), albumin level (HR 0.316, P = 0.034), and diabetes (HR 2.323, P = 0.027) were predictors of death in a multivariate analysis, while pacemaker implant within 30 days was not. Patients with AF who were anticoagulated had improved survival in a stratified Kaplan-Meier analysis compared with those who were not anticoagulated (P = 0.0001). CONCLUSION: AF, diabetes, and low albumin levels are independently associated with mortality after TAVR. In particular, patients with AF who are not anticoagulated are at highest risk for death. Efforts to identify AF and consider anticoagulation should be emphasized.

Heart failure in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a constellation of cardiovascular (CV) and non-CV manifestations. Even though CV complications such as accelerated atherosclerosis and elevated risk of myocardial infarction (MI) have been recognized for many years, there is limited evidence regarding SLE and its association with heart failure (HF). Traditional risk factors of atherosclerotic CV disease, as well as various SLE manifestations and therapies, independently or together, increase the risk of HF in this population. There is a need for sufficiently powered intervention studies focusing on specific risk factors to improve CV outcomes in SLE patients.

Pulmonary Capillary Wedge Pressure Patterns During Exercise Predict Exercise Capacity and Incident Heart Failure.

BACKGROUND: Single measurements of left ventricular filling pressure at rest lack sensitivity for identifying heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea on exertion. We hypothesized that exercise hemodynamic measurements (ie, changes in pulmonary capillary wedge pressure [PCWP] indexed to cardiac output [CO]) may more sensitively differentiate HFpEF and non-HFpEF disease states, reflect aerobic capacity, and forecast heart failure outcomes in individuals with normal PCWP at rest. METHODS AND RESULTS: We studied 175 patients referred for cardiopulmonary exercise testing with hemodynamic monitoring: controls (n=33), HFpEF with resting PCWP≥15 mm Hg (n=32), and patients with dyspnea on exertion with normal resting PCWP and left ventricular ejection fraction (DOE-nlrW; n=110). Across 1835 paired PCWP-CO measurements throughout exercise, we used regression techniques to define normative bounds of "PCWP/CO slope" in controls and tested the association of PCWP/CO slope with exercise capacity and composite cardiac outcomes (defined as cardiac death, incident resting PCWP elevation, or heart failure hospitalization) in the DOE-nlrW group. Relative to controls (PCWP/CO slope, 1.2±0.4 mm Hg/L/min), patients with HFpEF had a PCWP/CO slope of 3.4±1.9 mm Hg/L/min. We used a threshold (2 SD above the mean in controls) of 2 mm Hg/L/min to define abnormal. PCWP/CO slope >2 in DOE-nlrW patients was common (n=45/110) and was associated with reduced peak Vo2 (P<0.001) and adverse cardiac outcomes after adjustment for age, sex, and body mass index (hazard ratio, 3.47; P=0.03) at a median 5.3-year follow-up. CONCLUSIONS: Elevated PCWP/CO slope during exercise (>2 mm Hg/L/min) is common in DOE-nlrW and predicts exercise capacity and heart failure outcomes. These findings suggest that current definitions of HFpEF based on single measures during rest are insufficient and that assessment of exercise PCWP/CO slope may refine early HFpEF diagnosis.

Exercise oscillatory ventilation: Mechanisms and prognostic significance.

Alteration in breathing patterns characterized by cyclic variation of ventilation during rest and during exercise has been recognized in patients with advanced heart failure (HF) for nearly two centuries. Periodic breathing (PB) during exercise is known as exercise oscillatory ventilation (EOV) and is characterized by the periods of hyperpnea and hypopnea without interposed apnea. EOV is a non-invasive parameter detected during submaximal cardiopulmonary exercise testing. Presence of EOV during exercise in HF patients indicates significant impairment in resting and exercise hemodynamic parameters. EOV is also an independent risk factor for poor prognosis in HF patients both with reduced and preserved ejection fraction irrespective of other gas exchange variables. Circulatory delay, increased chemosensitivity, pulmonary congestion and increased ergoreflex signaling have been proposed as the mechanisms underlying the generation of EOV in HF patients. There is no proven treatment of EOV but its reversal has been noted with phosphodiesterase inhibitors, exercise training and acetazolamide in relatively small studies. In this review, we discuss the mechanistic basis of PB during exercise and the clinical implications of recognizing PB patterns in patients with HF.

Pulmonary Vascular Distensibility Predicts Pulmonary Hypertension Severity, Exercise Capacity, and Survival in Heart Failure.

BACKGROUND: Pulmonary vascular (PV) distensibility, defined as the percent increase in pulmonary vessel diameter per mm Hg increase in pressure, permits the pulmonary vessels to increase in size to accommodate increased blood flow. We hypothesized that PV distensibility is abnormally low in patients with heart failure (HF) and serves as an important determinant of right ventricular performance and exercise capacity. METHODS AND RESULTS: Patients with HF with preserved ejection fraction (n=48), HF with reduced ejection fraction (n=55), pulmonary arterial hypertension without left heart failure (n=18), and control subjects (n=30) underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and first-pass radionuclide ventriculography. PV distensibility was derived from 1257 matched measurements (mean±SD, 8.3±2.8 per subject) of pulmonary arterial pressure, pulmonary arterial wedge pressure and cardiac output. PV distensibility was lowest in the pulmonary arterial hypertension group (0.40±0.24% per mm Hg) and intermediate in the HF with preserved ejection fraction and HF with reduced ejection fraction groups (0.92±0.39 and 0.84±0.33% per mm Hg, respectively) compared to the control group (1.39±0.32% per mm Hg, P<0.0001 for all three). PV distensibility was associated with change in right ventricular ejection fraction (RVEF, ρ=0.39, P<0.0001) with exercise and was an independent predictor of peak VO2. PV distensibility also predicted cardiovascular mortality independent of peak VO2 in HF patients (n=103; Cox hazard ratio, 0.30; 95% confidence interval, 0.10-0.93; P=0.036). In a subset of patients with HF with reduced ejection fraction (n=26), 12 weeks of treatment with the pulmonary vasodilator sildenafil or placebo led to a 24.6% increase in PV distensibility (P=0.015) in the sildenafil group only. CONCLUSIONS: PV distensibility is reduced in patients with HF and pulmonary arterial hypertension and is closely related to RV systolic function during exercise, maximal exercise capacity, and survival. Furthermore, PV distensibility is modifiable with selective pulmonary vasodilator therapy and may represent an important target for therapy in selected HF patients with pulmonary hypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00309790.

Metabolic Profiling of Right Ventricular-Pulmonary Vascular Function Reveals Circulating Biomarkers of Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension and associated right ventricular (RV) dysfunction are important determinants of morbidity and mortality, which are optimally characterized by invasive hemodynamic measurements. OBJECTIVES: This study sought to determine whether metabolite profiling could identify plasma signatures of right ventricular-pulmonary vascular (RV-PV) dysfunction. METHODS: We measured plasma concentrations of 105 metabolites using targeted mass spectrometry in 71 individuals (discovery cohort) who underwent comprehensive physiological assessment with right-sided heart catheterization and radionuclide ventriculography at rest and during exercise. Our findings were validated in a second cohort undergoing invasive hemodynamic evaluations (n = 71), as well as in an independent cohort with or without known pulmonary arterial (PA) hypertension (n = 30). RESULTS: In the discovery cohort, 21 metabolites were associated with 2 or more hemodynamic indicators of RV-PV function (i.e., resting right atrial pressure, mean PA pressure, pulmonary vascular resistance [PVR], and PVR and PA pressure-flow response [ΔPQ] during exercise). We identified novel associations of RV-PV dysfunction with circulating indoleamine 2,3-dioxygenase (IDO)-dependent tryptophan metabolites (TMs), tricarboxylic acid intermediates, and purine metabolites and confirmed previously described associations with arginine-nitric oxide metabolic pathway constituents. IDO-TM levels were inversely related to RV ejection fraction and were particularly well correlated with exercise PVR and ΔPQ. Multisite sampling demonstrated transpulmonary release of IDO-TMs. IDO-TMs also identified RV-PV dysfunction in a validation cohort with known risk factors for pulmonary hypertension and in patients with established PA hypertension. CONCLUSIONS: Metabolic profiling identified reproducible signatures of RV-PV dysfunction, highlighting both new biomarkers and pathways for further functional characterization.

Recurrent candida prosthetic endocarditis over fifteen years managed with medical therapy and four valvular surgeries: a case report and review of literature.

BACKGROUND: Candida prosthetic endocarditis (CPE) is an uncommon disease involving less than 1 % of infective endocarditis patients and associated with high recurrence rate. Immunosuppresion, intravenous drug abuse, cardiac surgery and indwelling foreign bodies are the major risk factors for CPE. There are very few reported cases of CPE where more than one surgery was performed and there has generally been limited follow up on these cases. CASE PRESENTATION: We report a case of a 35 year old woman who had mitral valve annuloplasty complicated by recurrent episodes of CPE leading to multiple mitral valve replacements (MVR). She underwent MVR surgeries a total of four times over an eighteen year period and had good functionality during most of this time while being on antifungal suppressive treatment. This is a unique case in terms of numbers of surgeries performed, the length of the follow up and the involvement of three different Candida species. CONCLUSION: Current guidelines for the treatment of candida endocarditis recommend surgical treatment followed by long term antifungal therapy although the cure rate by all treatments is low. However we feel that based on this one case it is reasonable to consider multiple redo valve replacement surgeries in conjunction with antifungal treatment for selected patients stable enough to tolerate the surgery.

Mechanisms of exercise intolerance in heart failure with preserved ejection fraction: the role of abnormal peripheral oxygen extraction.

BACKGROUND: Exercise capacity as measured by peak oxygen uptake (Vo2) is similarly impaired in patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). However, characterization of how each component of Vo2 changes in response to incremental exercise in HFpEF versus HFrEF has not been previously defined. We hypothesized that abnormally low peripheral o2 extraction (arterio-mixed venous o2 content difference, [C(a-v)o2]) during exercise significantly contributes to impaired exercise capacity in HFpEF. METHODS AND RESULTS: We performed maximum incremental cardiopulmonary exercise testing with invasive hemodynamic monitoring on 104 patients with symptomatic NYHA II to IV heart failure (HFpEF, n=48, peak Vo2=13.9±0.5 mL kg(-1) min(-1), mean±SEM, and HFrEF, n=56, peak Vo2=12.1±0.5 mL kg(-1) min(-1)) and 24 control subjects (peak Vo2 27.0±1.7 mL kg(-1) min(-1)). Peak exercise C(a-v)o2 was lower in HFpEF compared with HFrEF (11.5±0.27 versus 13.5±0.34 mL/dL, respectively, P<0.0001), despite no differences in age, hemoglobin level, peak respiratory exchange ratio, Cao2, or cardiac filling pressures. Peak C(a-v)o2 and peak heart rate emerged as the leading predictors of peak Vo2 in HFpEF. Impaired peripheral o2 extraction was the predominant limiting factor to exercise capacity in 40% of patients with HFpEF and was closely related to elevated systemic blood pressure during exercise (r=0.49, P=0.0005). CONCLUSIONS: In the first study to directly measure C(a-v)o2 throughout exercise in HFpEF, HFrEF, and normals, we found that peak C(a-v)o2 was a major determinant of exercise capacity in HFpEF. The important functional limitation imposed by impaired o2 extraction may reflect intrinsic abnormalities in skeletal muscle or peripheral microvascular function, and represents a potential target for therapeutic intervention.