Nishant R. Shah

Percutaneous Circulatory Support in Cardiogenic Shock: Interventional Bridge to Recovery

Over the past 2 decades, innovation in the realm of mechanical ventricular assist devices (VADs) has altered the management of cardiogenic shock (CS). Percutaneous VADs (PVADs) allow emergent and effective ventricular unloading while providing sufficient systemic perfusion pressure to reverse end-organ dysfunction. Despite relatively few randomized trials evaluating these devices, some cardiovascular society guidelines recommend the use of PVADs in patients not responding to standard treatments for CS, including intra-aortic balloon pump (IABP) counterpulsation (Class IIa, Level of Evidence C).1 The purpose of this review is to highlight the spectrum of CS, to review modern PVADs as an interventional bridge to recovery, to discuss unique clinical issues related to PVAD support, and finally to offer a perspective on the future directions of acute mechanical circulatory support research. CS is a state of end-organ hypoperfusion caused by left ventricular (LV), right ventricular (RV), or biventricular myocardial injury resulting in systolic and/or diastolic myocardial pump failure. Myocardial infarction (MI) with LV failure remains the most common cause of CS. In general, CS complicates 8.6% of ST-segment elevation MIs (STEMI)2 and 2.5% of non–ST segment elevation MIs.3 Common causes of CS are listed in Table 1. View this table: Table 1. Common Causes of Cardiogenic Shock Clinically, CS is defined by both hemodynamic parameters (persistent hypotension [systolic blood pressure 18 mm Hg or RV end-diastolic pressure >10–15 mm Hg]) and clinical signs/symptoms of hypoperfusion (cool extremities, decreased urine output, and/or altered mental status). Inadequate systemic perfusion results in secondary lactic acidosis, catecholamine and neurohormone release, and activation of …

Echocardiography in the Management of Patients with Left Ventricular Assist Devices: Recommendations from the American Society of Echocardiography.

Raymond F. Stainback, MD, FASE, Chair, Jerry D. Estep, MD, FASE, Co-Chair, Deborah A. Agler, RCT, RDCS, FASE, Emma J. Birks, MD, PhD, Merri Bremer, RN, RDCS, EdD, FASE, Judy Hung, MD, FASE, James N. Kirkpatrick, MD, FASE, Joseph G. Rogers, MD, and Nishant R. Shah, MD, MSc, Houston, Texas; Cleveland, Ohio; Louisville, Kentucky; Rochester, Minnesota; Boston, Massachusetts; Philadelphia, Pennsylvania; and Durham, North Carolina

Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is Associated with Severely Impaired Coronary Flow Reserve, Not Obstructive Disease

Background: Cardiovascular disease (CVD) fatality rates are higher for women than for men, yet obstructive coronary artery disease (CAD) is less prevalent in women. Coronary flow reserve (CFR), an integrated measure of large- and small-vessel CAD and myocardial ischemia, identifies patients at risk for CVD death, but is not routinely measured in clinical practice. We sought to investigate the impact of sex, CFR, and angiographic CAD severity on adverse cardiovascular events. Methods: Consecutive patients (n=329, 43% women) referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography and with left ventricular ejection fraction >40% were followed (median, 3.0 years) for a composite end point of major adverse cardiovascular events, including cardiovascular death and hospitalization for nonfatal myocardial infarction or heart failure. The extent and severity of angiographic CAD were estimated by using the CAD prognostic index, and CFR was quantified by using positron emission tomography. Results: Although women in comparison with men had lower pretest clinical scores, rates of prior myocardial infarction, and burden of angiographic CAD (P<0.001), they demonstrated greater risk of CVD events, even after adjustment for traditional risk factors, imaging findings, and early revascularization (adjusted hazard ratio, 2.05; 95% confidence interval, 1.05–4.02; P=0.03). Impaired CFR was similarly present among women and men, but in patients with low CFR (<1.6, n=163), women showed a higher frequency of nonobstructive CAD, whereas men showed a higher frequency of severely obstructive CAD (P=0.002). After also adjusting for CFR, the effect of sex on outcomes was no longer significant. When stratified by sex and CFR, only women with severely impaired CFR demonstrated significantly increased adjusted risk of CVD events (P<0.0001, P for interaction=0.04). Conclusions: Women referred for coronary angiography had a significantly lower burden of obstructive CAD in comparison with men but were not protected from CVD events. Excess cardiovascular risk in women was independently associated with impaired CFR, representing a hidden biological risk, and a phenotype less amenable to revascularization. Impaired CFR, particularly absent severely obstructive CAD, may represent a novel target for CVD risk reduction.

Clinical outcomes after ventricular assist device implantation in adults with complex congenital heart disease

BACKGROUND There are minimal data regarding ventricular assist device (VAD) implantation in adult patients with complex congenital heart disease (CHD). METHODS The medical records of 6 adult patients with complex CHD who underwent VAD implantation were retrospectively analyzed to characterize pre-operative clinical status, implantation techniques and challenges, post-operative management, and post-operative outcomes. RESULTS All patients had a systemic right ventricle, including 2 with single-ventricle physiology. The average age at VAD implantation was 41 years. The implanted VADs included 1 HeartMate XVE, 3 HeartMate II (Thoratec Corp, Pleasanton, CA), 1 Jarvik 2000 (Jarvik Heart, New York, NY), and 1 HeartWare HVAD (HeartWare Inc, Framingham, MA). In-hospital outcomes included no sub-pulmonic ventricular failure, no VAD thrombosis or mechanical failure, 30-day mortality in 1 patient, non-fatal sub-arachnoid hemorrhage in 1 patient, and sustained ventricular tachycardia requiring unsynchronized direct current cardioversion in 1 patient. Of the 5 patients who survived to discharge, 1 patient received 171 days of VAD support before cardiac transplantation and survived for 1,484 days after transplantation; 1 patient received 262 days of VAD support before out-of-hospital death of unknown etiology; 1 patient had received VAD support for 988 days as of December 1, 2012, while awaiting a transplant; and 2 patients who received VADs as destination therapy had received 577 and 493 days of VAD support, respectively, and were still alive as of December 1, 2012. CONCLUSIONS This case series characterizes important post-operative management challenges and clinical outcomes associated with VAD implantation as a bridge-to-transplant or as destination therapy in adult patients with complex CHD.

Prognostic Value of Coronary Flow Reserve in Patients with Dialysis-Dependent ESRD

Capillary rarefaction of the coronary microcirculation is a consistent phenotype in patients with dialysis-dependent ESRD (dd-ESRD) and may help explain their excess mortality. Global coronary flow reserve (CFR) assessed by positron emission tomography (PET) is a noninvasive, quantitative marker of myocardial perfusion and ischemia that integrates the hemodynamic effects of epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. We tested whether global CFR provides risk stratification in patients with dd-ESRD. Consecutive patients with dd-ESRD clinically referred for myocardial perfusion PET imaging were retrospectively included, excluding patients with prior renal transplantation. Per-patient CFR was calculated as the ratio of stress to rest absolute myocardial blood flow. Multivariable Cox proportional hazards models, including age, overt cardiovascular disease, and myocardial scar/ischemia burden, were used to assess the independent association of global CFR with all-cause and cardiovascular mortality. The incremental value of global CFR was assessed with relative integrated discrimination index and net reclassification improvement. In 168 patients included, median global CFR was 1.4 (interquartile range, 1.2-1.8). During follow-up (median of 3 years), 36 patients died, including 21 cardiovascular deaths. Log-transformed global CFR independently associated with all-cause mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.14; P<0.001) and cardiovascular mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.15; P=0.002). For all-cause mortality, addition of global CFR resulted in risk reclassification in 27% of patients. Thus, global CFR may provide independent and incremental risk stratification for all-cause and cardiovascular mortality in patients with dd-ESRD.

Anomalous origin of the coronary artery arising from the opposite sinus: prevalence and outcomes in patients undergoing coronary CTA.

Aims The impact of coronary computed tomographic angiography (CTA) on management of anomalous origin of the coronary artery arising from the opposite sinus (ACAOS) remains uncertain. We examined the prevalence, anatomical characterization, and outcomes of ACAOS patients undergoing CTA. Methods and results Among 5991 patients referred for CTA at two tertiary hospitals between January 2004 and June 2014, we identified 103 patients (1.7% prevalence) with 110 ACAOS vessels. Mean age was 52 years (range 5–83, 63% male), with 55% previously known ACAOS and 45% discovered on CTA. ACAOS subtypes included: 39% interarterial (n = 40 anomalous right coronary artery, n = 3 anomalous left coronary artery), 38% retroaortic, 15% subpulmonic, 5% prepulmonic, and 2% other. ACAOS patients were assessed for symptoms, ischaemic test results, revascularization, all-cause or cardiovascular (CV) death, and myocardial infarction. CTAs were reviewed for ACAOS course, take-off height and angle, length and severity of proximal narrowing, intramural course, and obstructive coronary artery disease (CAD). In follow-up (median 5.8 years), there were 20 surgical revascularizations and 3 CV deaths. After adjusting for obstructive CAD (n = 21/103, 20%), variables associated with ACAOS revascularization included the following: CV symptoms, proximal vessel narrowing ≥50%, length of narrowing >5.4 mm, and an interarterial course. Conclusion The prevalence of ACAOS on CTA was 1.7%, including 45% of cases discovered incidentally. CTA provided excellent characterization of ACAOS features associated with coronary revascularization, including the length and severity of proximal vessel narrowing.

Prognostic value of coronary CTA vs. exercise treadmill testing: results from the Partners registry.

AIMS We sought to compare the complementary prognostic value of exercise treadmill testing (ETT) and coronary computed tomographic angiography (CTA) among patients referred for both exams. METHODS AND RESULTS We studied 582 patients without known coronary artery disease (CAD) who were clinically referred for ETT and CTA within 6 months. Patients were followed for cardiovascular (CV) death, non-fatal myocardial infarction (MI), or late revascularization (>90 days), stratified by Duke Treadmill Score (DTS) and CAD severity (≥50% stenosis). Mean age was 54 ± 13 years (63% male). In median follow-up of 40 months, there were 3 CV deaths, 7 non-fatal MIs, and 26 late revascularizations. ETT was inconclusive in 23%, positive in 31%, and negative in 46%. CTA demonstrated no CAD in 37%, non-obstructive CAD in 28%, and obstructive CAD in 35%. Among low-risk ETT patients (n = 326), there were 3 MI, 10 late revascularizations, and the frequent presence of non-obstructive (32%, n = 105) and obstructive CAD (27%, n = 88). When present, ETT features (i.e., angina, DTS, ischaemic electrocardiogram changes, and exercise capacity) individually failed to predict CV death/MI after adjustment for Morise score. Conversely, both obstructive CAD [HR 4.9 (1.0-23.3), P = 0.048] and CAD extent by segment involvement score >4 [HR 3.9 (1.0-15.2), P = 0.049] predicted increased risk for CV death or MI. CONCLUSION Patients with a low-risk ETT have an excellent prognosis at 40 months, despite the frequent presence of non-obstructive (32%) and obstructive (27%) CAD. In patients with an intermediate- to high-risk ETT (DTS <5), CTA can provide incremental risk stratification for future CV events.

Diagnostic and prognostic value of myocardial blood flow quantification as non-invasive indicator of cardiac allograft vasculopathy

Aims Cardiac allograft vasculopathy (CAV) is a leading cause of death in orthotopic heart transplant (OHT) survivors. Effective non-invasive screening methods are needed. Our aim was to investigate the added diagnostic and prognostic value of myocardial blood flow (MBF) to standard myocardial perfusion imaging (MPI) with positron emission tomography (PET) for CAV detection. Methods and results We studied 94 OHT recipients (prognostic cohort), including 66 who underwent invasive coronary angiography and PET within 1 year (diagnostic cohort). The ISHLT classification was used as standard definition for CAV. Positron emission tomography evaluation included semiquantitative MPI, quantitative MBF (mL/min/g), and left ventricular ejection fraction (LVEF). A PET CAV severity score (on a scale of 0-3) was modelled on the ISHLT criteria. Patients were followed for a median of 2.3 years for the occurrence of major adverse events (death, re-transplantation, acute coronary syndrome, and hospitalization for heart failure). Sensitivity, specificity, positive, and negative predictive value of semiquantitative PET perfusion alone for detecting moderate-severe CAV were 83% [52-98], 82% [69-91], 50% [27-73], and 96% [85-99], respectively {receiver operating characteristic (ROC area: 0.82 [0.70-0.95])}. These values improved to 83% [52-98], 93% [82-98], 71% [42-92], and 96% [97-99], respectively, when LVEF and stress MBF were added (ROC area: 0.88 [0.76-0.99]; P = 0.01). There were 20 major adverse events during follow-up. The annualized event rate was 5%, 9%, and 25% in patients with normal, mildly, and moderate-to-severely abnormal PET CAV grading (P < 0.001), respectively. Conclusion Multiparametric cardiac PET evaluation including quantification of MBF provides improved detection and gradation of CAV severity over standard myocardial perfusion assessment and is predictive of major adverse events.

Current State of Advanced Cardiovascular Imaging Training in the United States.

Rapid technological advances have made it challenging for trainees to gain independent interpretive competency in 1 or more of the cardiovascular imaging modalities during a standard 3-year cardiology fellowship. Consequently, many general cardiology fellows choose to dedicate at least 1 year of

Ranolazine in Symptomatic Diabetic Patients Without Obstructive Coronary Artery Disease: Impact on Microvascular and Diastolic Function

Background Treatments for patients with myocardial ischemia in the absence of angiographic obstructive coronary artery disease are limited. In these patients, particularly those with diabetes mellitus, diffuse coronary atherosclerosis and microvascular dysfunction is a common phenotype and may be accompanied by diastolic dysfunction. Our primary aim was to determine whether ranolazine would quantitatively improve exercise‐stimulated myocardial blood flow and cardiac function in symptomatic diabetic patients without obstructive coronary artery disease. Methods and Results We conducted a double‐blinded crossover trial with 1:1 random allocation to the order of ranolazine and placebo. At baseline and after each 4‐week treatment arm, left ventricular myocardial blood flow and coronary flow reserve (CFR; primary end point) were measured at rest and after supine bicycle exercise using 13N‐ammonia myocardial perfusion positron emission tomography. Resting echocardiography was also performed. Multilevel mixed‐effects linear regression was used to determine treatment effects. Thirty‐five patients met criteria for inclusion. Ranolazine did not significantly alter rest or postexercise left ventricular myocardial blood flow or CFR. However, patients with lower baseline CFR were more likely to experience improvement in CFR with ranolazine (r=−0.401, P=0.02) than with placebo (r=−0.188, P=0.28). In addition, ranolazine was associated with an improvement in E/septal e′ (P=0.001) and E/lateral e′ (P=0.01). Conclusions In symptomatic diabetic patients without obstructive coronary artery disease, ranolazine did not change exercise‐stimulated myocardial blood flow or CFR but did modestly improve diastolic function. Patients with more severe baseline impairment in CFR may derive more benefit from ranolazine. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01754259.